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Bibliography on: Microbiome

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 26 Jun 2019 at 01:34 Created: 

Microbiome

It has long been known that every multicellular organism coexists with large prokaryotic ecosystems — microbiomes — that completely cover its surfaces, external and internal. Recent studies have shown that these associated microbiomes are not mere contamination, but instead have profound effects upon the function and fitness of the multicellular organism. We now know that all MCEs are actually functional composites, holobionts, composed of more prokaryotic cells than eukaryotic cells and expressing more prokaryotic genes than eukaryotic genes. A full understanding of the biology of "individual" eukaryotes will now depend on an understanding of their associated microbiomes.

Created with PubMed® Query: microbiome[tiab] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-06-24

Langsetmo L, Johnson A, Demmer RT, et al (2019)

The Association between Objectively Measured Physical Activity and the Gut Microbiome among Older Community Dwelling Men.

The journal of nutrition, health & aging, 23(6):538-546.

OBJECTIVES: To determine the relationship between objectively measured physical activity (PA) and the gut microbiome among community-dwelling older men.

DESIGN: Cross-sectional study.

SETTING: Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16).

PARTICIPANTS: Eligible men (n=373, mean age 84 y) included participants with 5-day activity assessment with at least 90% wear time and analyzed stool samples.

MEASUREMENTS: PA was measured with the SenseWear Pro3 Armband and stool samples analyzed for 16S v4 rRNA marker genes using Illumina MiSeq technology. Armband data together with sex, height, and weight were used to estimate total steps, total energy expenditure, and level of activity. 16S data was analyzed using standard UPARSE workflow. Shannon and Inverse Simpson indices were measures of (within-participant) α-diversity. Weighted and unweighted Unifrac were measures of (between-participant) β-diversity. We used linear regression analysis, principal coordinate analysis, zero-inflated Gaussian models to assess association between PA and α-diversity, β-diversity, and specific taxa, respectively, with adjustments for age, race, BMI, clinical center, library size, and number of chronic conditions.

RESULTS: PA was not associated with α-diversity. There was a slight association between PA and β-diversity (in particular the second principal coordinate). Compared to those who were less active, those who had higher step counts had higher relative abundance of Cetobacterium and lower relative abundance of taxa from the genera Coprobacillus, Adlercreutzia, Erysipelotrichaceae CC-115 after multivariable adjustment including age, BMI, and chronic conditions. There was no consistent pattern by phylum.

CONCLUSION: There was a modest association between levels of PA and specific gut microbes among community-dwelling older men. The observed associations are consistent with the hypothesis that underlying health status and composition of the host microbiome are related.

RevDate: 2019-06-24

Knox NC, Forbes JD, Peterson CL, et al (2019)

The Gut Microbiome in Inflammatory Bowel Disease: Lessons Learned From Other Immune-Mediated Inflammatory Diseases.

The American journal of gastroenterology [Epub ahead of print].

There is a growing appreciation for the role of the gut microbiome in human health and disease. Aided by advances in sequencing technologies and analytical methods, recent research has shown the healthy gut microbiome to possess considerable diversity and functional capacity. Dysbiosis of the gut microbiota is believed to be involved in the pathogenesis of not only diseases that primarily affect the gastrointestinal tract but also other less obvious diseases, including neurologic, rheumatologic, metabolic, hepatic, and other illnesses. Chronic immune-mediated inflammatory diseases (IMIDs) represent a group of diseases that share many underlying etiological factors including genetics, aberrant immunological responses, and environmental factors. Gut dysbiosis has been reported to be common to IMIDs as a whole, and much effort is currently being directed toward elucidating microbiome-mediated disease mechanisms and their implications for causality. In this review, we discuss gut microbiome studies in several IMIDs and show how these studies can inform our understanding of the role of the gut microbiome in inflammatory bowel disease.

RevDate: 2019-06-24

Perkowski K, Baltaza W, Conn DB, et al (2019)

Examination of oral biofilm microbiota in patients using fixed orthodontic appliances in order to prevent risk factors for health complications.

Annals of agricultural and environmental medicine : AAEM, 26(2):231-235.

INTRODUCTION AND OBJECTIVE: In recent decades the use of orthodontic appliances in Poland has increased; however, data on their influence on changes of components of the microbiome connected with oral biofilm are scarce. The objective of this study was to evaluate oral microbiota in terms of their role as risk factors for health complications.

MATERIAL AND METHODS: The study included 100 patients treated with removable or fixed appliances. Oral hygiene and gingival health were determined, and periodontal swabs taken from each patient for parasitological, bacteriological and mycological microscopic and in vitro examinations.

RESULTS: Oral protists and various pathogenic and opportunistic bacterial and fungal strains were identified in the superficial layer of biofilm. A higher prevalence of bacteria, Enterococcus faecalis, E. faecium, Staphylococcus aureus and Escherichia coli, and various strains of yeast-like fungi from the Candida albicans group, occurred in patients treated with the fixed appliance than in those using a removable appliance or not treated orthodontically. In some periodontal samples from patients treated with fixed appliances, cysts of the Acanthamoeba spp. were found.

CONCLUSIONS: The use of orthodontic appliances alters the status of the oral cavity; it has impact on the colonization of oral biofilm by opportunistic/pathogenic strains, and increases the risk of their dissemination to various human tissues and organs. Pretreatment examination of oral microbiome, its monitoring particularly during treatment with fixed appliances, and preventive elimination of the potentially pathogenic strains to avoid health complications, are highly recommended, especially in patients with impaired immunity.

RevDate: 2019-06-24

Kellermayer R (2019)

Fecal microbiota transplantation: great potential with many challenges.

Translational gastroenterology and hepatology, 4:40 pii:tgh-04-2019.05.10.

In January of 2019, Samuel P. Costello and colleagues published a wonderfully executed, double blind placebo-controlled trial on fecal microbiota transplantation (FMT) versus autologous stool as placebo in mild to moderately active adult ulcerative colitis [UC: one type of inflammatory bowel disease (IBD)] patients. This review-commentary examines the current state of knowledge on human gut microbiome (live microbiota + their products and surrounding environment, i.e., fecal matter) and microbial therapeutics from a gastrointestinal (GI) clinician's standpoint. The varied forms of dysbiosis as the target of FMT, recipient donor and placebo considerations are also discussed in respect to randomized control trials in IBD [and the lack thereof in Crohn's disease (CD)] with this unconventional treatment modality.

RevDate: 2019-06-24

Jia B, Wang R, Zhang J, et al (2019)

Commentary: Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.

Frontiers in cellular and infection microbiology, 9:155.

RevDate: 2019-06-24

Naqib A, Poggi S, SJ Green (2019)

Deconstructing the Polymerase Chain Reaction II: an improved workflow and effects on artifact formation and primer degeneracy.

PeerJ, 7:e7121 pii:7121.

Polymerase chain reaction (PCR) amplification of complex microbial genomic DNA templates with degenerate primers can lead to distortion of the underlying community structure due to inefficient primer-template interactions leading to bias. We previously described a method of deconstructed PCR ("PEX PCR") to separate linear copying and exponential amplification stages of PCR to reduce PCR bias. In this manuscript, we describe an improved deconstructed PCR ("DePCR") protocol separating linear and exponential stages of PCR and allowing higher throughput of sample processing. We demonstrate that the new protocol shares the same benefits of the original and show that the protocol dramatically and significantly decreases the formation of chimeric sequences during PCR. By employing PCR with annealing temperature gradients, we further show that there is a strong negative correlation between annealing temperature and the evenness of primer utilization in a complex pool of degenerate primers. Shifting primer utilization patterns mirrored shifts in observed microbial community structure in a complex microbial DNA template. We further employed the DePCR method to amplify the same microbial DNA template independently with each primer variant from a degenerate primer pool. The non-degenerate primers generated a broad range of observed microbial communities, but some were highly similar to communities observed with degenerate primer pools. The same experiment conducted with standard PCR led to consistently divergent observed microbial community structure. The DePCR method is simple to perform, is limited to PCR mixes and cleanup steps, and is recommended for reactions in which degenerate primer pools are used or when mismatches between primers and template are possible.

RevDate: 2019-06-24

Wolfgang A, Taffner J, Guimarães RA, et al (2019)

Novel Strategies for Soil-Borne Diseases: Exploiting the Microbiome and Volatile-Based Mechanisms Toward Controlling Meloidogyne-Based Disease Complexes.

Frontiers in microbiology, 10:1296.

Under more intensified cropping conditions agriculture will face increasing incidences of soil-borne plant pests and pathogens, leading to increasingly higher yield losses world-wide. Soil-borne disease complexes, in particular, are especially difficult to control. In order to better understand soil-borne Meloidogyne-based disease complexes, we studied the volatile-based control mechanism of associated bacteria as well as the rhizospheric microbiome on Ugandan tomato plants presenting different levels of root-galling damage, using a multiphasic approach. The experimental design was based on representative samplings of healthy and infected tomato plants from two field locations in Uganda, to establish species collections and DNA libraries. Root galling symptoms on tomato resulted from a multispecies infection of root-knot nematodes (Meloidogyne spp.). Results revealed that 16.5% of the bacterial strain collection produced nematicidal volatile organic compounds (nVOC) active against Meloidogyne. Using SPME GC-MS, diverse VOC were identified, including sulfuric compounds, alkenes and one pyrazine. Around 28% of the bacterial strains were also antagonistic toward at least one fungal pathogen of the disease complex. However, antagonistic interactions appear highly specific. Nematicidal antagonists included Pseudomonas, Comamonas, and Variovorax and fungicidal antagonists belonged to Bacillus, which interestingly, were primarily recovered from healthy roots, while nematode antagonists were prominent in the rhizosphere and roots of diseased roots. In summary, all antagonists comprised up to 6.4% of the tomato root microbiota. In general, the microbiota of healthy and diseased root endospheres differed significantly in alpha and quantitative beta diversity indices. Bacteria-derived volatiles appear to provide a remarkable, yet wholly unexploited, potential to control Meloidogyne-based soil-borne disease complexes. The highly specific observed antagonism indicates that a combination of volatiles or VOC-producing bacteria are necessary to counter the range of pathogens involved in such complexes.

RevDate: 2019-06-24

Stinson LF, Boyce MC, Payne MS, et al (2019)

The Not-so-Sterile Womb: Evidence That the Human Fetus Is Exposed to Bacteria Prior to Birth.

Frontiers in microbiology, 10:1124.

The human microbiome includes trillions of bacteria, many of which play a vital role in host physiology. Numerous studies have now detected bacterial DNA in first-pass meconium and amniotic fluid samples, suggesting that the human microbiome may commence in utero. However, these data have remained contentious due to underlying contamination issues. Here, we have used a previously described method for reducing contamination in microbiome workflows to determine if there is a fetal bacterial microbiome beyond the level of background contamination. We recruited 50 women undergoing non-emergency cesarean section deliveries with no evidence of intra-uterine infection and collected first-pass meconium and amniotic fluid samples. Full-length 16S rRNA gene sequencing was performed using PacBio SMRT cell technology, to allow high resolution profiling of the fetal gut and amniotic fluid bacterial microbiomes. Levels of inflammatory cytokines were measured in amniotic fluid, and levels of immunomodulatory short chain fatty acids (SCFAs) were quantified in meconium. All meconium samples and most amniotic fluid samples (36/43) contained bacterial DNA. The meconium microbiome was dominated by reads that mapped to Pelomonas puraquae. Aside from this species, the meconium microbiome was remarkably heterogeneous between patients. The amniotic fluid microbiome was more diverse and contained mainly reads that mapped to typical skin commensals, including Propionibacterium acnes and Staphylococcus spp. All meconium samples contained acetate and propionate, at ratios similar to those previously reported in infants. P. puraquae reads were inversely correlated with meconium propionate levels. Amniotic fluid cytokine levels were associated with the amniotic fluid microbiome. Our results demonstrate that bacterial DNA and SCFAs are present in utero, and have the potential to influence the developing fetal immune system.

RevDate: 2019-06-23

Fouillen A, Grenier D, Barbeau J, et al (2019)

Selective bacterial degradation of the extracellular matrix attaching the gingiva to the tooth.

European journal of oral sciences [Epub ahead of print].

The junctional epithelium (JE) is a specialized portion of the gingiva that seals off the tooth-supporting tissues from the oral environment. This relationship is achieved via a unique adhesive extracellular matrix that is, in fact, a specialized basal lamina (sBL). Three unique proteins - amelotin (AMTN), odontogenic ameloblast-associated (ODAM), and secretory calcium-binding phosphoprotein proline-glutamine rich 1 (SCPPPQ1) - together with laminin-332 structure the supramolecular organization of this sBL and determine its adhesive capacity. Despite the constant challenge of the JE by the oral microbiome, little is known of the susceptibility of the sBL to bacterial degradation. Assays with trypsin-like proteases, as well as incubation with Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola, revealed that all constituents, except SCPPPQ1, were rapidly degraded. Porphyromonas gingivalis was also shown to alter the supramolecular network of reconstituted and native sBLs. These results provide evidence that proteolytic enzymes and selected gram-negative periodontopathogenic bacteria can attack this adhesive extracellular matrix, intimating that its degradation could contribute to progression of periodontal diseases.

RevDate: 2019-06-23

Bieber T (2019)

Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis.

Allergy [Epub ahead of print].

Atopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered a paradigmatic type 2 immunity (T2)-driven disease. Interleukin (IL)-4 and IL-13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks the binding of both cytokines to their receptors, a number of new pharmacologic entities have been designed to target both T2 cytokines and/or their receptors and/or receptor-associated signal transduction machinery such as Janus kinases. Recently, IL-13 has been suggested to be the key T2 cytokine driving inflammation in the periphery, while IL-4 may merely have a central effect. There is increasing evidence that this concept holds true for the inflammatory reaction underlying AD, where IL-13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function. This review provides an update on the role of IL-13 in AD and discusses the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-23

Patel J (2019)

The gut microbiome: a novel cardio-metabolic target?.

Cardiovascular research pii:5522130 [Epub ahead of print].

RevDate: 2019-06-23

Kim HE, Lee JJ, Lee MJ, et al (2019)

Analysis of microbiome in raw chicken meat from butcher shops and packaged products in South Korea to detect the potential risk of foodborne illness.

Food research international (Ottawa, Ont.), 122:517-527.

Chicken meat is one of the most widely consumed meats worldwide. The microbiota on the whole body of chicken is a potential source of foodborne pathogens that can be transmitted to humans during the preparation of raw meat. However, to date, there have been no studies comparing the microbiota of packaged chicken products and those of raw chicken carcasses from butcher shops, although such information could be useful for identifying sources of contamination in cases of food poisoning. We addressed this in the present study by analyzing the microbiota of 80 chicken meat samples collected from various butcher shops and processing plants in South Korea with the Illumina MiSeq system based on the 16S rRNA gene sequence. The bacterial amounts in chicken samples were estimated by quantitative real-time PCR. Although different microbial members were present in unpackaged meat from butcher shops as compared to those in packaged products from commercial sources, seasonal differences (sample obtained in January vs. July) in microbiota were more significant even in the packaged products from the same company. We also investigated the influence of contaminated foodborne pathogen on the indigenous microbiota (64 chicken samples) by artificially inoculated with Salmonella enterica serotype Virchow on chicken carcasses under various conditions, and carrying out 16S rRNA gene and whole metagenome sequencing. The amount of contaminated Salmonella in chicken meat samples was the highest and lowest in samples stored at 27 °C and 4 °C after washing, respectively. Additionally, the relative abundance of virulence genes was detected lower in samples stored at 4 °C after washing in both butcher shop and commercial samples. These results could be useful for reducing the risk of foodborne illness caused by cross-contamination during the preparation of chicken meat.

RevDate: 2019-06-23

Ticinesi A, Nouvenne A, T Meschi (2019)

Gut microbiome and kidney stone disease: not just an Oxalobacter story.

Kidney international, 96(1):25-27.

Intestinal regulation of oxalate absorption is a complex mechanism, not exclusively reliant on the oxalate-degrading anaerobe Oxalobacter formigenes. Using metagenomics, Miller et al. were able to describe a network of bacterial taxa co-occurring with Oxalobacter formigenes in fecal samples from non-stone forming controls and less represented in stone formers. These findings may help to illuminate why previous intervention studies with probiotics have failed to reduce the risk of hyperoxaluria, opening new possibilities for future research.

RevDate: 2019-06-22

Sheridan PO, Martin JC, Minton NP, et al (2019)

Heterologous gene expression in the human gut bacteria Eubacterium rectale and Roseburia inulinivorans by means of conjugative plasmids.

Anaerobe pii:S1075-9964(19)30105-2 [Epub ahead of print].

Commensal butyrate-producing bacteria in the Firmicutes phylum are abundant in the human intestine and are important for maintaining health. However, understanding of the metabolism and host interaction of these bacteria is limited by the lack of genetic modification techniques. Here we establish a protocol enabling the transfer of autonomously-replicating shuttle vectors by conjugative plasmid transfer from an Escherichia coli donor into representatives of an important sub-group of strictly anaerobic human colonic Firmicutes. Five different plasmid shuttle vectors were tested, each carrying a different origin of replication from Gram-positive bacteria. Plasmid pMTL83151 (pCB102 replicon) were successfully transferred into two strains of Eubacterium rectale, while pMTL83151 and pMTL82151 (pBP1 replicon) were transferred into Roseburia inulinivorans A2-194. Plasmids that carried a Streptococcus bovis JB1 glycoside hydrolase family 16 β-(1,3-1,4)-glucanase gene were constructed and conjugated into Roseburia inulinivorans A2-194 and Eubacterium rectale T1-815, resulting in successful heterologous expression of this introduced enzymatic activity in these two strains of butyrate-producing Firmicutes.

RevDate: 2019-06-22

White JF, Kingsley KL, Zhang Q, et al (2019)

Review: Endophytic Microbes and Their Potential Applications in Crop Management.

Pest management science [Epub ahead of print].

Endophytes are microbes (mostly bacteria and fungi) present in plants. Endophytic microbes are often functional in that they may carry nutrients from the soil into plants, modulate plant development, increase stress tolerance of plants, suppress virulence in pathogens, increase disease resistance in plants, and suppress development of competitor plant species. Endophytic microbes have been shown: 1) obtain nutrients in soils and transfer nutrients to plants in the rhizophagy cycle and other nutrient-transfer symbioses; 2) increase plant growth and development; 3) reduce oxidative stress of hosts; 4) protect plants from disease; 5) deter feeding by herbivores; and 6) suppress growth of competitor plant species. Because of the effective functions of endophytic microbes, we suggest that endophytic microbes may significantly reduce use of agrochemicals (fertilizers, fungicides, insecticides, and herbicides) in the cultivation of crop plants. The loss of endophytic microbes from crop plants during domestication and long-term cultivation could be remedied by transfer of endophytes from wild relatives of crops to crop species. Increasing atmospheric carbon dioxide levels could reduce the efficiency of the rhizophagy cycle due to repression of reactive oxygen used to extract nutrients from microbes in roots. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-22

Pusceddu MM, Stokes PJ, Wong A, et al (2019)

Sexually-dimorphic influence of neonatal antibiotics on bone.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society [Epub ahead of print].

The gut microbiome (GM) contributes to host development, metabolism, and disease. Perturbations in GM composition, elicited through chronic administration of oral antibiotics (Abx) or studied using germ-free (GF) environments, alter bone mass and microarchitecture. However, studies primarily involved chronic Abx exposure to adult mice prior to evaluating skeletal phenotype. Children are more prone to infection with bacterial pathogens than adults and are thus treated more frequently with broad-spectrum Abx; consequently, Abx treatment disproportionately occurs during periods of greatest skeletal plasticity to anabolic cues. Because early life exposures may exert long-lasting effects on adult health, we hypothesized that acute Abx administration during a developmentally-sensitive period would elicit lasting effects on skeletal phenotype. To test this hypothesis, neonatal mice were treated with Abx (P7-P23; oral gavage) or vehicle (water); GM composition, gut physiology, and bone structural and material properties was assessed in adulthood (8 weeks). We found sexually-dimorphic effects of neonatal Abx administration on GM composition, gut barrier permeability, and the skeleton, indicating a negative role for neonatal Abx on bone mass and quality. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-22

Lang S, Duan Y, Liu J, et al (2019)

Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis.

Hepatology (Baltimore, Md.) [Epub ahead of print].

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder and non-alcoholic controls using fungal-specific internal transcribed spacer (ITS) amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups whereas genus Penicillium dominated the mycobiome of non-alcoholic controls. We observed a lower diversity in the alcohol groups compared to controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to non-alcoholic controls. Within the alcoholic hepatitis patient cohort, patients with levels of ≥34 IU/ml, had a significantly lower 90-day survival (60%) compared to those with ASCA levels <34 IU/ml (80%) with an adjusted hazard ratio of 3.13 (95% CI 1.11-8.82, p=0.031). In conclusion, patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared to controls. Higher serum ASCA was associated with increased mortality in alcoholic hepatitis patients. Intestinal fungi may serve as a therapeutic target to improve survival and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-22

Zengler K, Hofmockel K, Baliga NS, et al (2019)

EcoFABs: advancing microbiome science through standardized fabricated ecosystems.

Nature methods pii:10.1038/s41592-019-0465-0 [Epub ahead of print].

RevDate: 2019-06-22

Ruff WE, Dehner C, Kim WJ, et al (2019)

Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity.

Cell host & microbe pii:S1931-3128(19)30248-3 [Epub ahead of print].

Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen β2-glycoprotein I (β2GPI). Autoantigen-reactive CD4+ memory T cell clones and an APS-derived, pathogenic monoclonal antibody cross-reacted with R. int mimotopes. Core-sequence-dependent anti-R. int mimotope IgG titers were significantly elevated in APS patients and correlated with anti-β2GPI IgG autoantibodies. R. int immunization of mice induced β2GPI-specific lymphocytes and autoantibodies. Oral gavage of susceptible mice with R. int induced anti-human β2GPI autoantibodies and autoimmune pathologies. Together, these data support a role for non-orthologous commensal-host cross-reactivity in the development and persistence of autoimmunity in APS, which may apply more broadly to human autoimmune disease.

RevDate: 2019-06-22

Glasl B, Bourne DG, Frade PR, et al (2019)

Microbial indicators of environmental perturbations in coral reef ecosystems.

Microbiome, 7(1):94 pii:10.1186/s40168-019-0705-7.

BACKGROUND: Coral reefs are facing unprecedented pressure on local and global scales. Sensitive and rapid markers for ecosystem stress are urgently needed to underpin effective management and restoration strategies. Although the fundamental contribution of microbes to the stability and functioning of coral reefs is widely recognised, it remains unclear how different reef microbiomes respond to environmental perturbations and whether microbiomes are sensitive enough to predict environmental anomalies that can lead to ecosystem stress. However, the lack of coral reef microbial baselines hinders our ability to study the link between shifts in microbiomes and ecosystem stress. In this study, we established a comprehensive microbial reference database for selected Great Barrier Reef sites to assess the diagnostic value of multiple free-living and host-associated reef microbiomes to infer the environmental state of coral reef ecosystems.

RESULTS: A comprehensive microbial reference database, originating from multiple coral reef microbiomes (i.e. seawater, sediment, corals, sponges and macroalgae), was generated by 16S rRNA gene sequencing for 381 samples collected over the course of 16 months. By coupling this database to environmental parameters, we showed that the seawater microbiome has the greatest diagnostic value to infer shifts in the surrounding reef environment. In fact, 56% of the observed compositional variation in the microbiome was explained by environmental parameters, and temporal successions in the seawater microbiome were characterised by uniform community assembly patterns. Host-associated microbiomes, in contrast, were five-times less responsive to the environment and their community assembly patterns were generally less uniform. By applying a suite of indicator value and machine learning approaches, we further showed that seawater microbial community data provide an accurate prediction of temperature and eutrophication state (i.e. chlorophyll concentration and turbidity).

CONCLUSION: Our results reveal that free-living microbial communities have a high potential to infer environmental parameters due to their environmental sensitivity and predictability. This highlights the diagnostic value of microorganisms and illustrates how long-term coral reef monitoring initiatives could be enhanced by incorporating assessments of microbial communities in seawater. We therefore recommend timely integration of microbial sampling into current coral reef monitoring initiatives.

RevDate: 2019-06-22

Zhang M, Differding MK, Benjamin-Neelon SE, et al (2019)

Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome.

Annals of clinical microbiology and antimicrobials, 18(1):18 pii:10.1186/s12941-019-0318-9.

BACKGROUND: Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants.

METHOD: In this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months.

RESULTS: Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05).

CONCLUSIONS: Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.

RevDate: 2019-06-22

Ojo-Okunola A, Claassen-Weitz S, Mwaikono KS, et al (2019)

Influence of Socio-Economic and Psychosocial Profiles on the Human Breast Milk Bacteriome of South African Women.

Nutrients, 11(6): pii:nu11061390.

The human breast milk (HBM) bacteriome is an important, continuous source of microbes to the neonate in early life, playing an important role in shaping the infant's intestinal bacteriome. Study of the composition of the HBM bacteriome is an emerging area of research, with little information available, particularly from low- and middle-income countries. The aim of this study was to characterize the diversity of bacterial communities in HBM samples collected between 6-10 weeks postpartum from lactating South African women and to study potential influencing factors of the bacteriome. Using 16S rRNA gene sequencing of samples from 554 women, we demonstrated that the HBM bacteriome was largely dominated by the phyla Firmicutes (mean relative abundance: 71.1%) and Actinobacteria (mean relative abundance: 16.4%). The most abundant genera identified from the HBM bacteriome were Streptococcus (mean relative abundance: 48.6%), Staphylococcus (mean relative abundance: 17.8%), Rothia (mean relative abundance: 5.8%), and Corynebacterium (mean relative abundance: 4.3%). "Core" bacterial genera including Corynebacterium, Streptococcus, Staphylococcus, Rothia, Veillonella, Gemella, Acinetobacter, Micrococcus and a genus belonging to the Enterobacteriaceae family were present in 80% of samples. HBM samples were classified, according to their bacteriome, into three major clusters, dominated by the genera Staphylococcus (cluster 1), a combination of Staphylococcus and Streptococcus (cluster 2), and Streptococcus (cluster 3). The cluster groups differed significantly for Shannon and chao1 richness indices. Bacterial interactions were studied using co-occurrence networks with positive associations observed between the abundances of Staphylococcus and Corynebacteria (members of the skin microflora) and between Streptococcus, Rothia, Veillonella, and Gemella (members of the oral microflora). HBM from older mothers had a higher Shannon diversity index. The study site was associated with differences in HBM bacteriome composition (permutational multivariate analysis of variance using distance matrices (PERMANOVA), p < 0.05). No other tested socio-demographic or psychosocial factors were associated with HBM bacterial composition.

RevDate: 2019-06-22

Sandefur K, Kahleova H, Desmond AN, et al (2019)

Crohn's Disease Remission with a Plant-Based Diet: A Case Report.

Nutrients, 11(6): pii:nu11061385.

Crohn's disease (CD) is a form of chronic inflammatory bowel disease (IBD). The etiology of CD is thought to be multi-factorial; genetic factors, dietary and environmental exposures, immune events, and dysfunction of the gut microbiome are all though to play a role. The prevalence of CD is increasing globally and is higher in countries with a Westernized diet and lifestyle. Several human trials have demonstrated that plant-based dietary therapies may have utility in both the treatment of acute CD flares and the maintenance of remission. This case study describes a young adult male with newly diagnosed CD who failed to enter clinical remission despite standard medical therapy. After switching to a diet based exclusively on grains, legumes, vegetables, and fruits, he entered clinical remission without need for medication and showed no signs of CD on follow-up colonoscopy.

RevDate: 2019-06-21

Wan YD, Zhu RX, Bian ZZ, et al (2019)

Improvement of Gut Microbiota by Inhibition of P38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Rats with Severe Acute Pancreatitis.

Medical science monitor : international medical journal of experimental and clinical research, 25:4609-4616 pii:914538.

BACKGROUND Gut microbiota dysbiosis plays a key role in pathogenesis of severe acute pancreatitis (SAP). In this study, we explored the protective effects of the p38 MAPK inhibitor, SB203580, against gut inflammation and microbiota dysbiosis induced by pancreatic duct injection with 3.5% sodium taurocholate in an SAP rat model. MATERIAL AND METHODS Ninety male Sprague-Dawley rats were randomly assigned to sham-operated, SAP model, and SAP plus SB203580 groups (n=30/group). Histological examination was conducted to assess gut and pancreatitis injury. The levels of amylase, D-lactate, diamine oxidase, tumor necrosis factor alpha, IL-6, IL-1ß, and phospho-p38MAPK in the plasma and intestine were evaluated at 3, 6, or 12 h after SAP induction. The gut microbiome was investigated based on16S rDNA gene sequencing at 12 h after SAP induction. RESULTS Histological examination revealed edema and inflammatory infiltrations in the pancreas and distal ileum. The expression of tumor necrosis factor alpha, IL-1ß, and IL-6 in plasma and distal ileum was increased in the SAP group, which were restored after treatment with SB203580. Significantly lower bacterial diversity and richness was found in the SAP group. In the SAP group, the abundance of Bacteroidetes and Firmicutes was decreased, and there was a higher proportion of Proteobacteria at the phylum level. The SAP plus SB203580 group exhibited significantly less damage to the gut microbiota, with higher bacterial diversity and a more normal proportion of intestinal microbiota. CONCLUSIONS SB203580 mediated suppression of the p38 MAPK signaling pathway via reduced gut inflammatory response and microbiota dysbiosis.

RevDate: 2019-06-21

Hughes RL, Marco ML, Hughes JP, et al (2019)

The Role of the Gut Microbiome in Predicting Response to Diet and the Development of Precision Nutrition Models-Part I: Overview of Current Methods.

Advances in nutrition (Bethesda, Md.) pii:5521427 [Epub ahead of print].

Health care is increasingly focused on health at the individual level. In the rapidly evolving field of precision nutrition, researchers aim to identify how genetics, epigenetics, and the microbiome interact to shape an individual's response to diet. With this understanding, personalized responses can be predicted and dietary advice can be tailored to the individual. With the integration of these complex sources of data, an important aspect of precision nutrition research is the methodology used for studying interindividual variability in response to diet. This article stands as the first in a 2-part review of current research investigating the contribution of the gut microbiota to interindividual variability in response to diet. Part I reviews the methods used by researchers to design and carry out such studies as well as the statistical and bioinformatic methods used to analyze results. Part II reviews the findings of these studies, discusses gaps in our current knowledge, and summarizes directions for future research. Taken together, these reviews summarize the current state of knowledge and provide a foundation for future research on the role of the gut microbiome in precision nutrition.

RevDate: 2019-06-21

Hughes RL, Kable ME, Marco M, et al (2019)

The Role of the Gut Microbiome in Predicting Response to Diet and the Development of Precision Nutrition Models. Part II: Results.

Advances in nutrition (Bethesda, Md.) pii:5521420 [Epub ahead of print].

The gut microbiota is increasingly implicated in the health and metabolism of its human host. The host's diet is a major component influencing the composition and function of the gut microbiota, and mounting evidence suggests that the composition and function of the gut microbiota influence the host's metabolic response to diet. This effect of the gut microbiota on personalized dietary response is a growing focus of precision nutrition research and may inform the effort to tailor dietary advice to the individual. Because the gut microbiota has been shown to be malleable to some extent, it may also allow for therapeutic alterations of the gut microbiota in order to alter response to certain dietary components. This article is the second in a 2-part review of the current research in the field of precision nutrition incorporating the gut microbiota into studies investigating interindividual variability in response to diet. Part I reviews the methods used by researchers to design and carry out such studies as well as analyze the results subsequently obtained. Part II reviews the findings of these studies and discusses the gaps in our current knowledge and directions for future research. The studies reviewed provide the current understanding in this field of research and a foundation from which we may build, utilizing and expanding upon the methods and results they present to inform future studies.

RevDate: 2019-06-21

Li Y, Xie Z, Gao T, et al (2019)

A holistic view of gallic acid-induced attenuation in colitis based on microbiome-metabolomics analysis.

Food & function [Epub ahead of print].

Gallic acid (GA), a plant phenol found in fruits and vegetables, has been recently reported to attenuate ulcerative colitis (UC). However, the mechanism of GA in UC remains unknown. In this study, we investigated the therapeutic effects of GA on UC from the perspective of gut microbiota and supervised the metabolic alterations in vivo with 1H NMR-based metabolomics, which can provide a holistic view to understand the functions of GA in UC. Rats with dextra sulfate sodium (DSS)-induced colitis were rectally administrated with GA (6 mg kg-1) for 8 consecutive days. 16S gene sequencing was performed on feces samples to obtain bacterial community information. Urine and feces samples were analyzed with 1H NMR spectroscopy, and short chain fatty acids (SCFAs) in feces and colon contents were detected with gas chromatography. Our results showed that UC syndromes in the GA group were significantly attenuated. The microbial alterations in the DSS group were characterized by a decrease of probiotic bacteria, such as Lactobacillaceae and Prevotellaceae, and an increase of some pathogenic species, mainly in the Firmicutes and Proteobacteria phyla. GA treatment could modulate the microbiota composition towards a similar proportion to the control group. Metabolic data further revealed that the GA-induced metabolic changes focus on increasing carbohydrate metabolism (gluco-related metabolism) and bile acid (BA) metabolism and decreasing amino acid metabolism, which also provides evidence for alteration of the microbiota because these feces metabolites are by-products of interactions between the host and the microbiota. These findings demonstrate GA-induced alterations in metabolic and bacterial profiles in DSS-colitis, providing new insight into the attenuation of GA in UC.

RevDate: 2019-06-21

Jeon J, Lourenco J, Kaiser E, et al (2019)

Dynamic Changes of Gut Microbiome and Immune Response During the Acute Stage of Stroke in a Pig Model (P14-012-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz052.P14-012-19.

Objectives: Stroke is a leading cause of mortality and disability in the United States. Secondary injuries induced by inflammation plays a critical role in stroke recovery. This study investigates gut microbiome changes during the acute stage of ischemic stroke to better understand the role of gut microbiome in inflammation in an ischemic stroke pig model.

Methods: Ischemic stroke was induced by middle cerebral artery occlusion in pigs (n = 7). Fecal samples were collected at pre-stoke (PRE), 1 (1DPS), 3 (3DPS), and 5 days post-stroke (5DPS) to measure gut microbiome composition. Blood samples were collected at 1DPS for white blood cell analysis.

Results: Ischemic stroke was confirmed by magnetic resonance imaging at 1DPS. The dominant pre-stroke fecal bacterial phyla (>1% relative abundance) were Firmicutes (89.2%), Bacteroidetes (3.7%), Actinobacteria (2.0%) and Proteobacteria (1.3%). This composition significantly (P < 0.05) differed at 3DPS with a decreased Firmicutes (68.1%) and increased Actinobacteria (3.70%) and Proteobacteria (19.0%), and a trending (P = 0.06) increase among Bacteroidetes (7.6%). At 5DPS, Bacteroidetes (7.6%) remained elevated, but Firmicutes (86.6%), Actinobacteria (2.0%) and Proteobacteria (0.7%) returned to levels similar to PRE. At 1DPS, the α-diversity measured by Shannon index and species evenness were both decreased (P < 0.05), suggesting that overall bacterial diversity decreased immediately after the stroke. β-diversity analysis showed a trend for overall differences over time (P = 0.07), but no differences between specific days were found. Elevated inflammation and neutrophil-to-lymphocyte ratio (NLR) following stroke event have been related to negative functional outcome in stroke patients. At 1DPS, a significant increase in NLR was observed in the stroke pigs compared to those at PRE (P < 0.05), suggesting initiation of inflammatory response following stroke.

Conclusions: Ischemic stroke altered the gut microbiome composition, reduced microbiome diversity and increased immune response in pigs. Future studies are warranted to investigate systemic and neural inflammation mediated by the alteration of the gut microbiome following ischemic stroke.

Funding Sources: The study was funded by the National Institute of Health and University of Georgia (Faculty Research Grant).

RevDate: 2019-06-21

Deehan E, Yang C, Perez-Munoz ME, et al (2019)

Precision Microbiome Modulation with Structurally Distinct Type-4 Resistant Starches (OR23-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR23-08-19.

Objectives: The gut microbiota is linked to a wide range of pathologies, making it a promising target for improving health. Modulation of the gut microbiota can be achieved by dietary fibers, such as resistant starches, which have demonstrated a role in the prevention of these diseases. However, it is unknown if targeted manipulation of gut microbiota composition, and especially function can be achieved by specific doses of structurally similar yet district fibers. The objective of this study was to compare the effect and dose-response of three different type-4 resistant starches (RS4s) on microbiome composition and function.

Methods: Using a randomized, double blind, placebo controlled, four arm design, 40 subjects were assigned to consume either one of three RS4s (derived from hi-maize, potato, or tapioca) or a digestible starch for 4 weeks. The fiber dose was raised each week from 0 to 50 g/d, and fecal samples were collected at the end of each week. Microbiota composition and SCFA were assessed by 16S RNA gene sequencing and gas chromatography, respectively.

Results: Maize and tapioca RS4s, at doses ≥35 g/d, significantly affected the global composition of the microbiota, decreasing α-diversity and increasing β-diversity compared to baseline. Interestingly, effects of RS4s on microbiota composition and fecal SCFA were distinct and reflected differences in RS4 structure. Maize RS4 enriched Operational Taxonomic Units related to Eubacterium rectale [100% ID], Ruminococcus spp [97.9% ID], and Bifidobacterium adolescentis [100% ID], and increased butyrate. Although there was overlap in the enrichment of B. adolescentis, tapioca RS4 enriched Parabacteroides distasonis [100% ID] and Eisenbergiella spp [94% ID] (but not E. rectale or Ruminococcus spp), and increased propionate. These affects were dose-dependent with a plateau at the 35 g/d dose. In contrast, potato RS4 and digestible starch did not significantly modulate the microbiome.

Conclusions: These findings provide essential information on how chemical differences in starch structure can result in specific and dose-dependent alterations of the gut microbiome, providing a basis for precision microbiome modulation through nutritional strategies.

Funding Sources: This work was supported by Ingredion Incorporated, and by the Campus Alberta Innovation Program, CIHR, and the Canada Foundation for Innovation.

RevDate: 2019-06-21

Wan J, Wu Y, Pham Q, et al (2019)

Gut Microbial Composition in Mice Fed Different Amount of Rice Resistant Starch (P21-031-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz041.P21-031-19.

Objectives: The aim of this study is to evaluate the effects of rice containing different levels of resistant starch on the gut microbiome using a rodent model.

Methods: Rice with low resistant starch (0.11%), medium resistant starch (1.07%) and high resistant starch (8.61%) were cooked, grounded into powders and used to formulate diet to represent all the carbohydrates in mice diet that consist of low fat (LF, 10 kcal %) or high fat (HF, 39 kcal %). C57BL/6 mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat and low resistant starch diet (LL); (2) high-fat and low resistant starch diet (HL); (3) low-fat and medium resistant starch diet (LM); (4) high-fat and medium resistant starch diet (HM); (5) low-fat and high resistant starch diet (LH); (6) high-fat and high resistant starch diet (HH). Mice were fed with diets for 8 weeks then gut microbiome composition was determined using 16S rDNA sequencing of cecal contents.

Results: We found that the gut microbiome was significantly different at different levels of resistant starch (P < 0.01) but not at different fat levels. OTU (operational taxonomic unit) richness was reduced in LF and HF high-resistant groups as compared to others. OTU diversity was reduced in LF and HF medium and high-resistant groups as compared to low-resistant groups. Decreased Firmicutes to Bacteroidetes ratio, which related to lower risk of obesity, was observed in mice fed LF and HF high-resistant diet as compared to others. Moreover, at the family level, LF, HF high-resistant diet mainly increased the abundances of Bacteroidaceae and S24_7, the bacteria positively correlated with SCFAs (short-chain fatty acids) levels. We also observed a decrease in abundances of Odoribacteraceae, Rikenellaceae, Lachnospiraceae, Ruminococcaceae and Desulfovibrionaceae in LF and HF high resistant starch group. Desulfovibrionaceae and genus Odoribecter in Odoribacteraceae are reported to be opportunistic pathogens, Lachnospiraceae, Ruminococcaceae, Odoribacteraceae and Rikenellaceae are associated with obesity.

Conclusions: Overall, our results demonstrated that resistant starch exerted concentration-dependent effect on the gut microbiome in mice which may have protective effect against obesity.

Funding Sources: USDA, ARS.

RevDate: 2019-06-21

Soares J, Pantoja-Feliciano I, Doherty L, et al (2019)

In Vitro Exploration of Healthy and Stressed Gut Microbiota Metabolism (P20-002-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-002-19.

Objectives: From a military perspective, the gut microbiome serves as an ideal tool to enhance Soldier gut and immune health and to improve survivability and performance. Our work employs in vitro tools as a means to elucidate systematic processes of colonic bacterial metabolism of dietary inputs under native and stressed conditions. This talk will focus on the use of in vitro fermentation to investigate both the prebiotic potential of cranberry proanthocyanidins (PAC) within a healthy microbiome and stress-induced alterations in microbial inter-species competition for fermentable fiber.

Methods: Fermentations were performed in triplicate, utilizing fecal inocula derived from at least three individuals, in a nutrient-rich anaerobic medium with sampling at 0 and 24 hrs. Within PAC supplementation studies, samples were analyzed for bacterial identification (16 s rRNA sequencing) and metabolite content (GC-FID and GC/MS). Stressed metabolism studies, which utilized fecal samples before and after a 21-day change in diet challenge (habitual vs. Meal Ready-to-Eat), employed media supplemented with resistant starch under ascending colon domain-specific conditions; samples taken were analyzed for bacterial identification (16 s rRNA) and enumeration of select organisms (qPCR).

Results: Bacterial population dynamics within PAC supplementation studies indicated a dose-dependent increase in several beneficial taxa, including Ruminococcus spp (P < 0.05). Phenolic metabolite generation as a function of PAC dosage identified several compounds associated with anti-inflammatory activity, including 3-(4-OH-phenyl) propionic acid (P < 0.001). Within stressed metabolism studies, Lactobacillus spp. growth was attenuated as a function of sudden change in diet (P ≤ 0.001), whereas growth of R. bromii was enhanced (P ≤ 0.05), indicating potential for an acute stressor to impact gut bacteria functional metabolism.

Conclusions: In vitro fermentation elucidated both a potential prebiotic effect of cranberry PAC on gut microbiota and the impact of sudden change in diet on inter-species competition for nutritional substrates. Understanding of gut microbiota metabolism dynamics could direct future dietary supplementation strategies to build resiliency against military-relevant stressors and offset negative impacts of dysbiosis.

Funding Sources: Defense Health Program.

RevDate: 2019-06-21

Kohlstadt I, Schmitt JF, R Watkins (2019)

Obesogenic Alterations in Adrenal Function and Neurotransmitter Balance Improved with Dietary Supplementation (P21-008-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz041.P21-008-19.

Objectives: Dysfunction of the HPA axis, as evidenced by alterations in the diurnal salivary cortisol rhythm, has been shown to contribute to the pathophysiology of obesity both directly by skewing body composition and indirectly by altering appetite and microbiome. The aim of this study was to assess the impact of a laboratory and clinical-guided dietary supplemental protocol on HPA axis dysfunction.

Methods: This study examines a cohort of 703 patients utilizing a clinical analysis of 1. Hypothalamic-pituitary-adrenal axis tests which were 4 point salivary cotisol, 2 point salivary DHEA, and 6 urinary neurotransmitters. 2. Self-reported Quality of Life questionnaire 3. Personalized dietary supplementation with neurotransmitter amino acid precursors and/or adrenal support monitored for 8 months.

Results: Pre and post test demonstrated improved sleep quality (47%, P < 0.05); increased serotonin by 172% (P < 0.05); increased norepinephrine (P < 0.05); improved adrenal tone with increased morning cortisol (P < 0.05) and decreased evening cortisol (P < 0.08).

Conclusions: A personalized medicine approach consisting of symptom analysis, noninvasive laboratory testing and dietary supplementation improved parameters of HPA axis dysfunction. Lab-guided personalized medicine may be able to diagnose early and treatable HPA axis dysfunction and in this way curtail a known pathway to obesity.

Funding Sources: No grant funding was received. The research is an IRB-exempted analysis of data collected by Sanesco International, Inc.

RevDate: 2019-06-21

Jackson M, D Jewell (2019)

Fiber Type Determines Feline Gut Microbiome Metabolism and Bioactive Lipid Profiles in Feces (P20-034-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-034-19.

Objectives: Dietary fiber consists of indigestible carbohydrate. A distinction in fiber classification is "soluble" (SOL) vs "insoluble" (INSOL). Fiber is not absorbed in the small intestine, but arrives intact to the colon where it is metabolized by microbiota. Metabolomics screening determined the impact of foods with SOL vs INSOL fiber on microbiome metabolites and bioactive lipids in feces from cats.

Methods: Healthy cats were housed in environments promoting social interaction with other cats and people, had access to natural light varying with season, opportunity to exercise and were fed to maintain body weight. Collections under IACUC approved protocols. Two foods produced: SOL (5.2% crude fiber analyzed) and INSOL (10.1% crude fiber analyzed). SOL had citrus & beet pulps, oat bran and barley. INSOL had pea & tomato fiber, and cellulose. Randomized design, with cats assigned SOL (n = 15), INSOL (n = 16). Cats fed for 12 weeks. Metabolomics by LC-MS, short chain fatty acids (SCFA) by GC-FID (feces). Data analyzed by mixed model, paired t-test, Hotelling's T2 test and correlation. Significant when P < 0.05.

Results: SOL increased flavonoids in the feces, likely from fiber-bound sources; these were metabolized by gut microbiota to postbiotics. Only SOL increased SCFA acetate and propionate but not butyrate. INSOL decreased, and SOL increased putrefactive branched SCFA. Polyamine putrefaction products were decreased by INSOL relative to SOL; fecal polyamine levels predicted serum levels. Fecal microbial metabolites of resistant starch, polyphenols and redox congeners were all correlated to fecal taurine across both foods. INSOL significantly decreased the N-acyl classes of fecal endocannabinoids while leaving the O-acyl class unchanged. SOL increased the O-acyl class. Fecal anti-inflammatory fatty acid esters of hydroxystearate (FAHSA; linoleic, oleic and palmitic) were significantly increased by INSOL relative to SOL. Fecal 9/13 hydroxyoctadecadienoates (HODE) were increased by INSOL relative to SOL, but the 9-10/12-13 dihydroxyoctadecaenoates (DiHOME) were not affected.

Conclusions: There are apparent microbiome benefits to both SOL and INSOL fibers. The results here increase awareness of the importance of fiber for felines and further the effort to optimize fiber type and quantity in foods for cats.

Funding Sources: Hill's Pet Nutrition.

RevDate: 2019-06-21

Hirvonen J, Salli K, Putaala H, et al (2019)

Selective Utilization of Human Milk Oligosaccharides 2'-FL and 3-FL by Probiotic Bacteria Resulting in Different Metabolite Production by These Bacteria (P20-012-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-012-19.

Objectives: Human breast milk contains a high quantity of oligosaccharides (HMOs) which are not digested by infants but are selectively utilized by beneficial gut microbes such as Bifidobacterium species. The gut microbiome in breast-fed infants is dominated by Bifidobacterium species, whereas formula-fed infants have a higher representation of Bacteroides and Enterobacteria species. The aim of this study was to evaluate the ability of various potentially pathogenic bacteria and commercially available probiotic strains to grow using the HMOs 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL), glucose, lactose or galacto-oligosaccharide (GOS) as a sole carbon source. We also compared the production of short-chain fatty acids (SCFAs) and lactic acid during the fermentation of 2'-FL by B. infantis, B. bifidum and Bacteroides strains.

Methods: Bacterial growth was monitored by measuring the absorbance at 600 nm every 30 min for 24 h using the automatic Bioscreen© C system under anaerobic conditions in culture media containing 1% 2'-FL, 3-FL, glucose, lactose or GOS as a sole carbon source. Metabolites were analyzed by chromatographic methods in spent culture media after over-night growth of bacterial strains with 1% 2'-FL.

Results: Only certain bifidobacteria strains, B. infantis and B. bifidum, were able to utilize 2'-FL and 3-FL, whereas other tested Lactobacillus and Bifidobacterium strains as well as pathogenic bacteria grew with all other carbon sources. We also confirmed that Bacteroides fragilis, B. thetaiotaomicron and B. vulgatus strains utilized HMO. Distinct SCFA and lactic acid quantities were observed between Bifidobacterium and Bacteroides strains in 2'-FL fermentation. For instance, acetic and lactic acids were produced at much higher levels in Bifidobacterium than in Bacteroides, and propionic acid was produced at low level only in Bacteroides.

Conclusions: These results show the selectivity of 2'-FL and 3-FL utilization in certain Bifidobacterium and Bacteroides strains, which is translated to differences in metabolite production between these individual HMO-utilizing bacteria. Further studies will enlighten the role and potential benefits of HMOs as a selective substrate for gut microbes, as well as for competition and cross-feeding of microbial metabolites among gut species.

Funding Sources: This research was funded by DuPont Nutrition and Health.

RevDate: 2019-06-21

Patterson M, Fong JN, Wang W, et al (2019)

The Interrelationship Between the Gut Microbiome and Glucose Homeostasis Following Boiled and Chilled Potato Consumption (P20-020-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-020-19.

Objectives: Many factors influence the gut microbiome which in turn mediates physiological responses following food intake, especially when fermentable fibers such as resistant starch (RS) are consumed. Here we examined the relationship body composition and diet on gut microbiome diversity and composition in females. We also compared the effects of glucose and insulin following boiled (∼6 g RS) and chilled (∼12 g RS) potato intake on the gut microbiome.

Methods: Using a randomized cross-over study design 250 g of both boiled and chilled Russet potatoes were consumed on two separate visits with a one-week wash-out period. Fasting and postprandial (15, 30, 60, and 120 min) blood were collected for area under the curve (AUC(0-120)) glucose and insulin calculation. Prior to visit one stool and three-day food records were collected. At visit one anthropometrics and body composition (% fat mass (%FM) and lean mass (%LM)) using air displacement plethysmograph were assessed. Microbiome profiling via 16Sv3-4 sequencing identified bacterial diversity and composition in the stool. BMI, %FM, %LM, mean energy and nutrients, and AUC(0-120) glucose and insulin following the consumption of each potato were grouped into tertiles then compared to microbiome profiles using Kruskal-Wallis nonparametric tests.

Results: Twenty-four healthy females (mean age 28.8 ± 5.9 yr and BMI of 31.8 ± 7.4 kg/m2) completed the study. Females with a lower AUC(0-120) insulin following chilled potato intake had a higher Shannon diversity index (5.8 vs 4.9; P = .033) and Lentisphaerae abundance (3.3 vs ≤ 0.1; P = .005). Higher Actinobacteria (120 vs < 33) was associated with lower AUC(0-120) insulin (P = .025) following boiled potato intake. Higher %LM (> 54%) was associated with Lentisphaerae abundance (P = .036). BMI, %FM, diet, AUC(0-120) glucose following intake of both potatoes, and AUC insulin(0-120) following boiled potato intake did not correlate with specific microbiome profiles.

Conclusions: These data indicate that microbiome diversity is correlated with reduced insulin response following the intake of potatoes rich in RS, which may be a result of the bacterial fermentation of RS. Lentisphaerae and Actinobacteria abundance were also related to glycemic control.

Funding Sources: The Alliance for Potato Research and Education and Texas Woman's University Small Grants Program.

RevDate: 2019-06-21

Henrick B, Chew S, Mitchell R, et al (2019)

Restoring Bifidobacterium Infantis EVC001 to the Infant Gut Microbiome Significantly Reduces Intestinal Inflammation (OR12-01-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz049.OR12-01-19.

Objectives: Several seminal publications identify that Bifidobacterium longum subsp. infantis (B. infantis) has uniquely evolved to be the predominant strain in the breastfed infant gut; however, recent cohort studies indicate it is now far less abundant in infants born in industrialized nations, along with increased abundance of potentially pathogenic bacteria and gut dysbiosis. Importantly, recent clinical studies show enteric dysbiosis during the first 100 days of life can lead to higher risk of allergic and autoimmune-mediated disorders later in life. Given the importance of the microbiome for immune system development, we investigated the effect of B. infantis EVC001 consumption on intestinal inflammation in a cohort of healthy, term infants.

Methods: Forty (n = 40) infants were randomly selected from the previously conducted clinical study in which healthy, exclusively breastfed infants were either fed B. infantis EVC001 daily for 21 days, starting at day 7 postpartum, or received breastmilk alone. Stool samples were collected at multiple times postnatally and analyzed for cytokine production using a multiplex system and calprotectin ELISA.

Results: Baseline analysis indicated infants randomized to the EVC001 group produced naturally higher levels of IL2, IL5, IL6, IL10, TNFa and IFNg and lower levels of IL1b (all P < 0.01); however, by day 40, infants fed EVC001 produced significantly decreased cytokines, IL1b, IL6, IL8, IL22, TNFa and IFNg (all P < 0.0001) and IL-5 (P = 0.024), and at day 60 postpartum (all P < 0.001) and IL5 (P = 0.013). Fecal calprotectin concentration was significantly decreased in infants whose gut microbiome contained Bifidobacterium (P = 9.61e-05).

Conclusions: This study is the first to demonstrate a significant impact of B. infantis EVC001 on immune homeostasis in breastfed infants during a critical window of immune system development. Infants fed EVC001 produced significantly less proinflammatory cytokines and fecal calprotectin compared to control infants. Notably, TNFa, IL1b, and IFNg, which increase intestinal permeability, were significantly elevated in control infants. This may play an important mechanistic role in explaining the chronic intestinal inflammation observed in infants not colonized with B. infantis. These critical data provide a new understanding of the role of the infant gut microbiome in immune system development and provide novel applications to address chronic inflammation through modulation of gut dysbiosis.

Funding Sources: Industry funded.

RevDate: 2019-06-21

Piccolo B, Krishnan S, Shankar K, et al (2019)

An 8-week Controlled Feeding Trial Based on the 2010 Dietary Guidelines for Americans Has Minimal Effect on the Fecal Microbiota in Overweight and Obese Women (FS11-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.FS11-08-19.

Objectives: To determine whether a high quality diet based on the 2010 Dietary Guidelines of America (DGA) alters the composition of the fecal microbiome in individuals at risk for cardiometabolic disease, compared to a diet based on a typical American diet (TAD).

Methods: A total of 52 overweight and obese women were enrolled in a randomized, double-blind, controlled feeding trial. Women were randomly assigned to the DGA or TAD group (n = 28 DGA and 24 TAD). Diets matched each participant's estimated energy requirement and subjects remained weight-stable. The DGA diet was based on the 2010 DGA food-group recommendations, whereas the TAD diet was based on the average adult intake patterns from the NHANES 2009-2010 survey. Participants provided a stool sample 1-week prior to intervention (W0), within the second week of diet intervention (W2), and at the final week of intervention (W8). Microbial profiles were assessed using 16S rRNA amplicon sequencing and expressed as median % relative abundance. Data analyses were performed using standardized pipelines (QIIME 1.9 and R packages). False Discovery Rate (FDR) was set at 0.2.

Results: No differences were found in α- and β-diversity indices at the operational taxomonic unit (OTU) level by diet assignment at W0, and no taxa were differentially abundant at FDR < 0.2. Similarly, α- and β-diversity indices (OTU level) were not altered by diet within W2 or W8. A single OTU within the Ruminococcus genera was higher in TAD at both W2 (TAD = 0.014%; DGA = 0.00%) and W8 (TAD = 0.017%; DGA = 0.00%; FDR < 0.05), and the Adlercreutzia genera from the Actinobacteria phyla was also higher in TAD at both W2 (TAD = 0.027%; DGA = 0.001%) and W8 (TAD = 0.022%; DGA = 0.002%). No within-diet differences between W0 and W2, and W0 and W8 were observed in any α- and β-diversity indices tested. When adjusting for W0 relative abundances, 10 OTUs were altered by diet at W2 and 39 OTUs were altered at W8.

Conclusions: A weight-maintaining diet based on the 2010 DGA minimally differed in the fecal microbiota compared to a weight-maintaining typical American diet. Results herein suggests differences in food-based dietary patterns does not have a large effect on the composition of the fecal microbiota in humans.

Funding Sources: Supported by National Dairy Council; Campbell Soup Co.; USDA-ARS Projects 2032-51530-022-00D and 6026-51000-010-05S.

RevDate: 2019-06-21

van der Merwe M, Sharma S, Caldwell J, et al (2019)

Diet Modification and Not Timed Feeding Strategies Result in Intestinal Microbiome Alterations (P21-030-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz041.P21-030-19.

Objectives: Time-restricted feeding strategies have been shown to normalize obesity parameters, even under high fat feeding conditions. The objective of this study is to examine whether timed feeding alters parameters of gut health or intestinal microbiome composition.

Methods: C57BL/6 male mice were randomized to Chow or a high fat diet (HFD) for 6 weeks, followed by a switch from HFD to 1) Chow (sChow), 2) Purified Vegan - Daniel Fast (DF), 3) HFD ad lib, 4) HFD time restricted (TRF), 5) HFD alternative day fasting (ADF), or 6) HFD 60% caloric restriction (CR) for an additional 8 weeks.

Results: We observed that body mass gain was reduced for all intervention groups (P ≤ 0.0001). Small intestinal length and cecal weight were increased in Chow, sChow and DF (P ≤ 0.02), while total cecal short chain fatty acid (SCFA) concentration was non-significantly increased for all groups consuming the HFD. Proprionate was specifically increased in the Chow, sChow and DF groups (P ≤ 0.02). Chow fed microbiota remained stable in taxonomic composition and alpha diversity (Shannon diversity index) throughout the study. HF fed microbiota displayed lower alpha diversity along with reduced phylum levels of Bacteroidetes and increase Firmicutes. Animals switched from HF to Chow demonstrated a rapid transition in taxonomic composition, alpha, and beta diversity that initially resembled HF, but clustered closely with Chow by weeks 4 and 8 of intervention. After 8 weeks on the respective dietary protocols, alpha diversity of the DF was most similar to Chow fed animals and also resulted in the largest increase in Bacteriodetes and largest decrease in Firmicutes. Beta diversity (weighted UniFrac) showed Chow, sChow, and DF clustered together, while high fat fed groups (HF, CR, ADF, and TRF) clustered. Compared with HF controls, CR and TRF led to a relative increase in the classes Clostridia, Deferribacteres and Deltaproteobacteria. The taxonomic composition and alpha diversity of ADF fasting resembled HF under fed conditions, while ADF under fasting conditions more closely resembled CR and TRF.

Conclusions: In conclusion, timed feeding on a high fat diet did not result in significant changes in the microbiome, demonstrating that diet, and not fasting is the major determinant for microbiome composition.

Funding Sources: University of Memphis & Children's Foundation Research Institute, Memphis.

RevDate: 2019-06-21

Yeung OY, Ng YF, Chiou J, et al (2019)

A Pilot Study to Determine the Gut Microbiota of Hong Kong Infants Fed with Breast-milk And/or Infant Formula (P11-101-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.P11-101-19.

Objectives: Gut microbiome in newborn infants affect their gut health and future development. The major nutrient sources for infants aged 2-4 months are breast-milk or infant formula, hence it is worth investigating whether exclusively breastfed or infant formula-fed does affect the early development of the gut microbiota communities. Metagenomics has been applied to analyse the infant fecal samples in the United State and some European countries, however, similar studies were limited in Asia and especially Hong Kong.

Methods: Three groups of infants aged 2-4 months which were exclusively breastfed (BF), exclusively infant formula-fed (IF) or mix-fed with breast-milk and infant formula (MF) were recruited. Genomic DNA from the fecal sample and breast-milk was extracted and subjected to 16S rRNA next-generation sequencing to understand the gut microbiota profile, the difference of microbiota diversity and community abundance in these three feeding groups. The sequencing results were processed using pipelines Mothur and Qiime2.

Results: Overall the breast-milk showed higher alpha-diversity than the fecal samples. The 3 predominant Phyla were Proteobacteria, Firmicutes and Bacteroidetes within the fecal samples from all feeding patterns while the 3 dominant Phyla were Firmicutes, Proteobacteria and Actinobacteria in the breastmilk. Higher abundance of the well-known immune-modulating Genera Bifidobacterium and Lactobacillus were found in the fecal samples of BF and MF groups than the IF group whereas IF group harboured highest abundance of Genus Clostridium among 3 fecal groups. A PCoA based on unweighted UniFrac distance showed that the microbiota from the breastmilk clustered and distinctly separated from those of fecal samples. Moreover, the microbiota of MF subjects were close to BF subjects from the PCoA analysis.

Conclusions: Our preliminary results suggested that partial feeding with breast-milk could still maintain the major gut community composition as in the BF group. Feeding pattern affect the gut microbiota in Hong Kong infants aged 2-4 month and probiotic genera Bifidobacterium and Lactobacillus were found in the breast-milk, and fecal samples of BF and MF groups.

Funding Sources: Health and Medical Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region.

RevDate: 2019-06-21

Lebovitz A (2019)

Assessment of Diet via Food and Gut Microbiome Interactions (P20-036-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-036-19.

Objectives: The goal of this project was to understand how compounds naturally present in foods interact with the bacteria in the human gut microbiome.

Methods: Information on the compounds in different foods was obtained from FooDB. Microbiome pathway information was obtained from BioCyc. This information was synthesized into a web interface built with Flask. The interface allows a user to select a combination of food items. Upon selection, the user is presented with all microbiome reactions for which the constituent compounds of the foods are substrates, and the respective metabolic pathways of which they are part. The computations were done using Python. The interface was applied to investigate the ketogenic diet. Two ketogenic one-day meal plans were generated via an online tool (eatthismuch.com). The meal plans were entered into a macronutrient tracker "myfitnesspal," and modified to ensure similar macronutrient distributions. The average difference between the macronutrient content of the diets was 11.6%. The interface was used to determine the number of microbiome pathways in which a food compound served as a substrate.

Results: The following is a list of the foods in each of the meal plans and the number of interacting microbiome pathways. The first ketogenic meal plan consisted of: breakfast - 367 (bacon, eggs, butter); lunch - 547 (tuna, tomato, spinach); dinner - 362 (pork chop, cauliflower) and a snack - 327 (macadamia) yielding 581 unique bacterial pathways. The second meal plan consisted of: breakfast - 367 (bacon, eggs, butter); lunch - 382 (chicken, avocado); dinner - 339 (meatballs, cheese) and a snack - 357 (yogurt, cashews) yielding 428 unique bacterial pathways. This reflects a 30.3% difference between the two meal plans in interacting pathways. Excluding snacks, the highest number of interacting pathways was with a vegetable/fish meal (547) while the lowest was with a meat/cheese meal (339).

Conclusions: An assumption in many studies regarding diet is that two diets of similar macronutrient compositions will have similar physiological effects on the microbiome. However, the differences in the total number of interacting bacterial pathways between the two macronutrient similar ketogenic diets suggests that the effects on the microbiome are more complex, suggesting a new approach to the study of diet.

Funding Sources: N/A.

RevDate: 2019-06-21

Doherty L, Whitman J, Arcidiacono S, et al (2019)

Method for Modeling the Small Intestine and Resident Microbiome Through in Vitro Fermentation (P20-001-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-001-19.

Objectives: The human small intestine is a complex and dynamic organ tasked with enzymatic digestion and absorption of nutrients. Design of a small intestine model can provide detailed systematic knowledge of these processes; model design challenges include differential pH and oxygen availability along the length of the small intestine, food-dependent host secretion of digestive compounds, complex nutrient absorption processes, and microbiome interactions with both food and host. Numerous in vitro models have been developed to simulate the small intestine, but physiological relevance is limited. Here, we present an in vitro fermentation model of the small intestine to include microbiota and enhance physiological relevance.

Methods: A stepwise biofidelic model design approach was implemented with initial stages consisting of simulating ileum conditions, including pH and residence time, utilizing an automated bioreactor system for real-time monitoring and control of fermentation parameters, with incorporation of digestive enzymes and bile acids for breakdown of food inputs. Nutrient absorption, simulated using hollow-fiber columns to emulate passive diffusion, was initially optimized using small molecules to mimic dietary digestion byproducts; validation with food components, such as starch or whey powder, is planned. A mock microbial community, with organisms selected to represent major phyla and functions of the small intestine microbiota, was designed, implemented, and characterized in fermentations representing "fed-state" ileum conditions.

Results: Design and validation of the model with mock food components will be presented, along with steps taken to integrate in situ nutrient absorption and mock microbial community. Initial characterization of the microbial community indicates synergistic growth dynamics and nutrient utilization under "fed-state" conditions.

Conclusions: These efforts will be the foundation for our long-term goal of simulating the small intestine to complement our large intestine fermentation model, jA2COB, creating a complete in vitro fermentation model of the lower GI tract. Insight gleaned from this model, alone or in concert with in vivo studies, can inform nutritional strategies to restore and maintain host gut homeostasis.

Funding Sources: Funded by U.S. Army NSRDEC core applied research funds.

RevDate: 2019-06-21

Johnson A, Vangay P, D Knights (2019)

Dietary Patterns Correspond with Microbiome Composition (FS07-02-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.FS07-02-19.

Objectives: Previous studies have defined dietary patterns for comparison with microbiome features using factor analysis from food frequency questionnaires. In this study, we applied a new tree-based method to directly define dietary patterns from 24-hour food records. We aimed to determine if these patterns corresponded with microbial features.

Methods: Daily fecal samples and daily 24-hour food records (ASA24-2016) were collected from 32 healthy adults over 17 days. Dietary patterns were derived using all reported foods for each subject. Foods were arranged into a tree structure using USDA food groups. Tree-based weighted Unifrac food distances (QIIME 1.9.1) were used for principal coordinate analysis to define five dietary patterns. Each pattern was named after its most influential food groups. Average microbiome composition was determined from metagenomic sequencing. Dietary patterns were compared with subjects' average microbiome composition using correlation analysis. Spearman correlations were corrected for multiple comparisons within each taxonomy level. Constrained redundancy analysis (RDA) was used to determine the explanatory power of dietary patterns.

Results: Four of the five most discriminatory dietary patterns (DPs) were associated with microbial taxa (A). DP1 was positively correlated with an unclassified family in the order Burkholderiales and negatively correlated with the species Lachnospiraceae bacterium TF01-11. DP3, DP4, DP5 were most representative of a western diet. DP3 was negatively correlated with family Pasteurellaceae. DP4 was positively correlated with family Erysipelotrichaceae and negatively correlated with family Sutterellaceae. DP5 was positively correlated with members of class Bacteroidia including two specific Bacteroides speciesHMSC073E02 and HMSC067B03. Constrained RDA using the five dietary patterns revealed a gradient of Phylum Bacteroidetes along an axis driven by DP3, DP4, and DP5 (B).

Conclusions: The dietary patterns derived using our tree-based method reveal relationships between diet microbial taxa. In agreement with previous studies, our tree-based patterns show that the western diet corresponds to increased Bacteroidetes, demonstrating the utility of this method.

Funding Sources: Funding for this study was provided by General Mills.

RevDate: 2019-06-21

Ortega-Santos C, Tucker W, Brown C, et al (2019)

The Impact of Exercise on Gut Microbiota Diversity During a Period of Increased Caloric Intake Characteristic of the Winter Holiday Period (P21-029-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz041.P21-029-19.

Objectives: The winter holiday period is associated with weight gain from overconsumption of calories from fat and sugar. Such short-term lifestyle change has the ability to decrease diversity of the gut microbiome and enhance the harvest of energy from the hosts' diet, both of which are relevant factors in obesity. Exercise may influence gut microbial diversity and prevent diet induced obesity related health outcomes. The study aim to determine the impact of exercise on taxonomic diversity of the gut microbiota (GM) and cardiometabolic health parameters after four weeks of consuming a fat-sugar supplemented diet.

Methods: Healthy overweight/obese (BMI 29.8 ± 3.5 kg/m2, age 29 ± 7 yrs, waist circumference (WC) 99.8 ± 10 cm) males (n = 18) supplemented their diet with 2 donuts per day (606 kcal, 50% fat, 46% carbs, 4% protein), 6 days/week, for 4 weeks. Subjects were randomized to sedentary control (n = 4) or 1000 kcal/week on a cycle ergometer 4 days/week of supervised exercise (n = 14). We measured WC (cm), flow mediated dilation (FMD, %) and insulin resistance (HOMA-IR). GM diversity was analyzed, in stool samples collected pre- and post-intervention, with DADA2 and vegan, and visualized with ggplot in R. SILVA v.132 was used for taxonomic assignment. Differences in GM alpha (Shannon Index) and beta (Bray-Curtis) diversity were evaluated with Mann-Whitney U and Permutational Multivariate Analysis of Variance (PERMANOVA) tests.

Results: Microbial diversity analysis revealed no significant (P > 0.05) alpha (Shannon Index) or beta diversity (Bray-Curtis) differences between the control and exercise group after 4 weeks intervention. GM alpha and beta diversity also did not differ (P > 0.05) by HOMA-IR and FMD categories. We did observe that participants with a lower WC (<102 cm) had a significantly (P < 0.05) different microbial beta diversity than men with a WC of 102-109.99 cm but not compared to those with a WC > 110 cm.

Conclusions: In this study, exercise training during 4 weeks of consuming a fat-sugar supplemented diet did not appear to influence GM diversity. However, beta-diversity was heterogeneous across WC classes suggesting a potential link between central adiposity and GM community structure. Further studies with a larger sample size should be done to confirm these findings.

Funding Sources: This study was partially funded by the Arizona State University Graduate and Professional Student Association Research Program.

RevDate: 2019-06-21

Casaburi G, Karav S, Frese S, et al (2019)

Gut Barrier Function Is Improved in Infants Colonized by Bifidobacterium Longum Subsp. Infantis EVC001 (FS04-05-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.FS04-05-19.

Objectives: The gut epithelium is single-celled barrier that employs many different mechanisms that together provide the first line of defense to physically separate the gut epithelium from our gut microbiome. Notably, the epithelial barrier is protected by a mucin layer providing a physical barrier limiting pathogen access to the epithelial monolayer. We sought to assess how changes in the gut microbiome resulting from colonization by a single strain of Bifidobacterium longum subsp. infantis EVC001 could alter gut barrier function.

Methods: Fecal samples from this trial were assessed for: (1) endotoxin (lipopolysaccharide) concentration; (2) functional contributions to the gut microbiome by shotgun metagenome sequencing; and (3) fecal glycan profiles by mass spectrometry to assess gut epithelial barrier integrity via breakdown of colonic mucin glycoproteins.

Results: Colonization with Bifidobacterium, including B. infantis EVC001, showed a significant four-fold reduction in fecal endoxtoxin levels and reductions in fecal inflammatory markers (P < 0.05). Shotgun metagenomics identified LPS-producing Enterobacteriaceae as the most significant contributor of virulence factors in the infant gut metagenome. These bacteria (primarily E. coli and Klebsiella spp.) were also significantly correlated with both mucolytic bacteria (e.g., Bacteroides) and the signatures of mucin breakdown, as assessed by mass spectrometric quantification of colonic mucin-derived glycans. Five different colonic-mucin specific glycans (3_1_1_0, 2_1_2_0, 2_1_1_1, 2_1_1_0, and 1_1_0_1) were significantly associated with microbiome composition (P < 0.05). Overall mucin glycans were inversely correlated with Bifidobacteriaceae abundance (Spearman's rho -0.66, FDR-corrected P value 0.04).

Conclusions: Complex interactions between the degradation of gut barrier function (e.g., mucin), the production of pro-inflammatory endotoxins, and the risk of infection by these bacteria coming in close contact with the gut epithelium suggest that B. infantis EVC001 can play a role in reducing these combined risks for neonates.

Funding Sources: This work was funded by Evolve Biosystems, Inc.

RevDate: 2019-06-21

Aguilar-Lopez M, Wetzel C, MacDonald A, et al (2019)

Differential Effects of Mother's Own Milk, Donor Human Milk and Formula Feeding on the Fecal Microbiota of Preterm Infants During Their Stay in the Neonatal Intensive Care Unit (FS04-06-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.FS04-06-19.

Objectives: Preterm infants (PTI) are at risk for many complications including growth retardation, and co-morbidities, such as necrotizing enterocolitis. Microbiome composition is influenced by diet and other environmental factors or medical treatments. The use of mother's own milk (MOM) or donor human milk (DHM) is recommended over preterm formula (PF). However, when there is insufficient human milk (HM), PF is used. The objective of this study was to evaluate how each type of feed (MOM, DHM and PF) affects PTI gut microbiota composition during the infant's Neonatal Intensive Care Unit (NICU) stay.

Methods: This cohort study followed PTI from birth until discharge from the NICU. Medical records, weekly weight and daily feed volume were recorded. Stool samples (n = 551) were collected from the infant's diaper. Total DNA was extracted to assess microbiome composition, V3-V4 regions of 16S rRNA gene were amplified and sequenced using Illumina HiSeq and data were analyzed in Qiime2.

Results: PTI (n = 97; 63% female) were enrolled with mean gestational age (GA) of 29 ± 2.45 weeks, birth weight of 1.27 ± 0.43 kg, and 78% delivered by C-section. Infants were discharged at 37 ± 2.06 weeks corrected GA (cGA) weighing 2.69 ± 0.57 kg. At birth, PTI from black mothers (27%) had higher (P < 0.05) microbiota diversity (observed OTUs) than other ethnicities. No differences in microbiota were found for sex or mode of delivery in the first 14d postpartum. PF was not fed prior to 34 weeks cGA. Over time, microbiota beta diversity differentiated by cGA and type of feeding. In HM-fed PTI, when > 50% MOM was consumed, the abundance of Clostridium, Enterococcus, and Staphylococcus was higher (P < 0.05) than DHM. When > 50% DHM was fed, Bifidobacteium, Paeniclostridium, Staphylococcus and Veillonela increased (P < 0.05) compared to > 50% MOM. In PTI fed both HM and PF, in those consuming > 33% PF, the abundance of Clostridium difficile was higher and Staphylococcuslower than either MOM or DHM (P < 0.05).

Conclusions: The development of fecal microbiota of PTI was modulated by cGA, such that abundance and diversity increased over time. The fecal microbiota was differently modified by consumption of human milk, either MOM or DHM, versus PF. Ongoing studies are investigating the effect of milk fortifiers and other NICU environmental factors on the gut microbiota.

Funding Sources: Supported by a seed grant from Carle Foundation Hospital and University of Illinois and a CONACyT Graduate Fellowship.

RevDate: 2019-06-21

Brown A, Kaiser K, Keitt A, et al (2019)

Science Dialogue Mapping of Knowledge and Knowledge Gaps Related to the Effects of Dairy Intake on Human Cardiovascular Disease (P13-002-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz036.P13-002-19.

Objectives: Dairy has been described ranging from superfood to poison, but arguments, assumptions, and data used to justify these labels are not always clear. This project used "dialogue mapping" (DMing) to extract and summarize scientific points of (dis)agreement from an expert panel.

Methods: A day-long panel convened 8 experts with complimentary expertise in nutrition, obesity, and CVD. Discussions were documented through DMing, in which a meeting is summarized in real time to capture relationships among the panelists' thoughts. DMing explicitly, logically, and visually connects propositions, points, and counterpoints, even if discussed at different times, and helps identify whether experts agree and why. The map was distilled into key points and propositions (ongoing). Experts discussed two propositions: Consumption of full-fat dairy products, 1) in part because of their saturated fat levels, should be kept to a minimum for the purposes of reducing the risks of heart disease, or 2) despite their saturated fat levels, need not be kept to a minimum for the purposes of reducing the risks of heart disease.

Results: A preliminary map summary shows the panel discussed several expected topics, like LDL, HDL, and contributions of dairy fat to energy intake. Other points were discussed briefly or robustly, such as specific dairy bioactives (e.g., butyrate, calcium, CLA, MCT, proteins); biobehavioral components (e.g., whether dietary fat is self-regulating); and other topics (e.g., inflammation, microbiome, microRNAs).Two evidentiary issues emerged: 1) individual variability: whether recommendations should be targeted only to those at high CVD risk; and 2) quality of evidence: whether data on CVD endpoints and dairy intake are sufficient to make reliable conclusions - positive or negative - about full-fat dairy and CVD.Several procedural improvements were identified, including using a single proposition to be supported or refuted rather than two competing propositions.

Conclusions: DMing elicited a robust conversation, documenting views on topics about the relation between dairy intake and CVD. Two outstanding evidentiary concerns are: dairy-fat recommendations may need more individualization, and much long-term dairy-CVD data may not be robust enough for conclusions.

Funding Sources: Dairy Management, Inc.

RevDate: 2019-06-21

Berry S, Valdes A, Davies R, et al (2019)

Predicting Personal Metabolic Responses to Food Using Multi-omics Machine Learning in over 1000 Twins and Singletons from the UK and US: The PREDICT I Study (OR31-01-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz037.OR31-01-19.

Objectives: Glycemic, insulinemic and lipemic postprandial responses are multi-factorial and contribute to diabetes, obesity and cardiovascular disease. The aim of the PREDICT I study is to assess the genetic, metabolic, metagenomic, and meal-context contribution to postprandial responses, integrating the metabolic burden and gut microbiome to predict individual responses to food using a machine learning algorithm.

Methods: A multi-center dietary intervention study of 1000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from the US, assessed postprandial (0-6 h) metabolic responses to sequential mixed-nutrient dietary challenges in the clinic. Baseline data included metabolomics, genomics, gut metagenomics and DXA body composition. Glycemic responses to 5 duplicate isocaloric meals of different macronutrient content and self-selected meals (>100,000), were tested at home using a continuous glucose monitor (CGM). Interim analysis of the genetic contributions was performed in 110 identical and 25 non-identical twin pairs.

Results: Inter-individual variability in postprandial metabolic responses (glucose, insulin and triacylglycerol (TG)) was high in the clinic setting: incremental area under the curve IQR (median) was; glucose (0-2 h) 2.09 (1.95) mmol/L.h, insulin (0-2 h) 47.0 (67.6) mIU/L.h and TG (0-6 h) 2.34 (2.38) mmol/L.h. The unadjusted genetic contribution for the glucose, insulin and TG responses were 54%, 29% and 27% respectively. A predictive algorithm was developed and interim analyses, using at home CGM data, found that 46% of overall variation in glycemic responses could be predicted from meal content, meal context and individual baseline characteristics excluding genetic and microbiome factors. Only 29% of variation could be explained by the macronutrient content of the meal.

Conclusions: This is the most comprehensive postprandial study performed to date. The large and modifiable variation in metabolic responses to identical meals in healthy people explains why 'one size fits all' nutritional guidelines are problematic. By collecting information on glucose responses to >100,000 meals we will have excellent power to use machine learning to optimise and predict individual responses to foods.

Funding Sources: NIHR, Wellcome Trust, Zoe Global Ltd.

RevDate: 2019-06-21

Abernathy B, Blekhman R, Schoenfuss T, et al (2019)

Changes in the Gut Microbiome Contribute to Changes in Tissue Gene Expression in Rats Fed Prebiotic Dietary Fibers (P15-022-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz037.P15-022-19.

Objectives: We investigated the intersection between the gut microbiome and gene expression of colon and liver tissues in rats, using prebiotic dietary fibers to modulate the gut microbiome and elicit health benefits to the host.

Methods: Male Wistar rats were fed normal fat (NF) or high fat (HF, 51% fat by kcal) diets containing various fibers (6% fiber + 3% cellulose, by weight); including cellulose (NFC and HFC, non-fermentable), polylactose (HFPL, a novel prebiotic), and polydextrose (HFPD, an established prebiotic). After 10 weeks, tissues were harvested. Transcriptome analysis was performed by RNA sequencing of colon and liver tissues, and cecal contents were utilized for 16S microbiome sequencing. Analyses were conducted in R using DESeq2, DADA2, and phyloseq.

Results: Analysis of the gut microbiome revealed an increased abundance of probiotic genera, Bifidobacterium and Lactobacillus, in HFPL fed animals when compared to all other groups. These species are galactose fermenters which synthesize short chain fatty acids (SCFAs). This increased taxonomical abundance correlated with an increased FFar3 (SCFA receptor) expression in the colon. This suggests increased FFar3 signaling, leading to increased energy expenditure and GLP-1 and PYY secretion. Additionally, HFPL and HFPD groups had a decreased Firmicutes: Bacteroidetes ratio, which is associated with reduced adiposity due to the Bacteroidetes phylum being poor carbohydrate metabolizers, resulting in reduced energy uptake, yet increased SCFA synthesis. Bacteriodetes are also able to survive in SCFA and bile acid rich environments and are involved in the recycling of bile acids which negatively regulates cholesterol synthesis. This corresponds to reduced liver cholesterol and cholesterol synthesis pathway expression in the HFPL group. Further, liver gene expression revealed reduced lipid synthesis and increased lipid oxidation pathway gene expression in the HFPL group, corresponding to the reduction in fatty liver found in this group.

Conclusions: Prebiotic dietary fibers elicit changes in the gut microbiome and gene expression in liver and colon. Changes in gene expression correlated with the abundance of beneficial gut bacteria, providing a connection between the gut microbiome and health benefits to the host.

Funding Sources: Midwest Dairy Association.

RevDate: 2019-06-21

Um C, Lichtman C, Stevens V, et al (2019)

A Pilot Study to Assess Stool Sample Collection Methods for Gut Microbiome Research in Large Prospective Cohort Studies (FS07-01-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz036.FS07-01-19.

Objectives: Colonic microbiota can be modified by diet and other environmental exposures that are associated with risk of cancer and other diseases. In addition, the stool metabolome represents products formed by gut microbial utilization of foods, nutrients, and other compounds. The collection of stool samples for analyses of the microbiome and metabolome in prospective cohort studies may lead to a better understanding of diet and other factors in disease etiology.Most studies of the gut microbiome and metabolome have been small clinical studies and relied on the collection of stool samples that were quickly flash-frozen and stored with no preservative. However, this method of collection is not feasible in large epidemiologic studies in which participants would self-collect and ship samples to a central repository. Other methods may preclude metabolomic analyses or result in a limited amount of stool.

Methods: We designed a pilot study to inform stool collection procedures for participants enrolled in a nationwide prospective cohort study. In this pilot study, stool samples will be collected by 10 volunteers who will aliquot their sample into: 1) OMNIgene Gut collection kit, 2) 95% ethanol collection kit, (3) Fecal Occult Blood Test cards, and (4) a vial for fresh-frozen sample with no solution (i.e., the gold standard in this analysis). Fresh-frozen samples will be shipped overnight on dry ice to a central biorepository. The remaining samples will be: 1) shipped overnight on cold packs; 2) shipped overnight at ambient temperature; 3) shipped overnight after 4 days at ambient temperature; and 4) shipped overnight at ambient temperature, followed by 4-day incubation at 50 °C to mimic maximum shipment temperature. The reproducibility, stability, and accuracy of 16S sequencing and metabolomics in stool will be compared among the collection kits, and shipping and storage conditions.

Results: Initial results are anticipated by June 2019.

Conclusions: The findings of this pilot study will inform future stool collection among Cancer Prevention Study-3 (CPS-3) participants, which, when analyzed with food frequency questionnaire data, will broaden our understanding of the role of diet in cancer risk.

Funding Sources: The American Cancer Society funds the creation, maintenance, and updating of CPS-3.

RevDate: 2019-06-21

Rodriguez D, Brubaker M, Park E, et al (2019)

Dietary Intervention with Black Raspberries to Reduce Colitis Symptoms in Mice Fed Either Standard AIN93G Diet or the Total Western Diet (P05-021-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz030.P05-021-19.

Objectives: Approximately 1.4 million people suffer from inflammatory bowel disease, which is a major risk factor for developing colitis associated colorectal cancer (CAC). Dietary interventions with the goal to reduce colon inflammation and encourage gut microbiome homeostasis may be a strategy to reduce the risk of CAC. The antioxidants and anti-inflammatory compounds present in black raspberries (BRB) have demonstrated protective effects in the colon epithelium and may alter the composition of the gut microbiome. Previously, we showed that dietary supplementation with black raspberries significantly suppressed colitis and colon tumorigenesis promoted by the consumption of a Western type diet in mice. The goal of this study was to compare the efficacy of dietary intervention with whole, freeze-dried black raspberries on colitis and colon tumorigenesis in mice consuming either a standard diet or a Western type diet that emulates typical U.S. nutrient intakes.

Methods: C57BL/6 J male and female mice were fed a standard diet (AIN93G) or the total Western diet (TWD) supplemented with 0 to 10% (w/w) black raspberry powder for a total of 16 weeks. All mice were dosed with axozymethane and provided 1% dextran sodium sulfate in drinking water for 10 days to promote colonic inflammation and tumorigenesis.

Results: As previously observed, mice fed TWD experienced more pronounced symptoms of colitis with a 40% increase in the disease activity index (DAI) score. Preliminary analyses suggest that dietary supplementation with 10% BRB suppressed the DAI score in mice fed TWD such that the colitis symptoms in these mice were not apparently different compared to the AIN93G-fed controls. However, addition of 10% BRB did not appear to provide a benefit to mice fed the AIN basal diet. Composition of the fecal microbiome over the course of disease development will be determined by standard 16S rRNA sequencing, and assessment of tumor outcome is ongoing.

Conclusions: Consumption of a Western type diet increased symptoms of colitis, whereas dietary supplementation with 10% BRB appeared to ameliorate TWD-enhanced colitis in mice.

Funding Sources: USDA NIFA Grant# 2018-67017-27516 and UAES Project UTA-1178.

RevDate: 2019-06-21

Tindall A, McLimans C, Petersen K, et al (2019)

Walnuts and Vegetable Oils Differentially Affect the Gut Microbiome and Associations with Cardiovascular Risk Factors (OR29-06-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.OR29-06-19.

Objectives: To examine gut bacterial composition following a higher-saturated fatty acids (SFA) run-in, standard Western diet (SWD) and 3 study diets where SFA was replaced with: whole walnuts (WD); vegetable oils in a fatty acid matched diet devoid of walnuts (WFMD); vegetable oils in an oleic acid replaces α-linolenic acid (ALA) diet (ORAD) and devoid of walnuts. Correlations between the bacterial composition and cardiovascular disease (CVD) risk factors were also explored.

Methods: Adults at CVD risk (n = 42) were included in this secondary analysis of a randomized, crossover, controlled-feeding study that reported improvements in CVD risk factors. Only significantly changed risk factors were correlated with significantly enriched bacteria. Fecal collections followed a 2-week run-in diet and three 6-week diet periods. Linear discriminant analysis Effect Size plots were used to determine enriched taxa.

Results: Following the WD, Roseburia (mean relative abundance = 4.2%, LDA = 4, P = 0.0008), Eubacterium eligensgroup (1.4%, 4, 0.05), Lachnospiraceae UCG001 (1.2%, 3, 0.03), Lachnospiraceae UCG004 (1.0%, 3, 0.04) and Leuconostocaceae (0.03%, 3, 0.05) were abundant relative to the SWD. Relative to the SWD, Roseburia (mean relative abundance = 3.6%, LDA = 4, P = 0.02) and Eubacterium eligensgroup (1.5%, 3, 0.02) were enriched following the WFMD, and following the ORAD Clostridialesvadin BB60 (0.3%, 2, 0.04) was most abundant. Significant associations existed between enriched bacteria following the WD and CVD risk factors. Eubacterium eligens correlated with brachial (R = -0.5, P = 0.0009) and central mean arterial pressure (MAP; -0.5, 0.002), and central diastolic blood pressure (cDBP; -0.5, 0.0006). Lachnospiraceae correlated with brachial (R = -0.4, P = 0.02) and central MAP (-0.4, 0.02), cDBP (-0.3, 0.04), total cholesterol (TC; -0.4, 0.03), and non-HDL-C (-0.4, 0.02). Leuconostocaceae correlated with brachial (R = 0.3, P = 0.03) and central MAP (0.3, 0.03).

Conclusions: Similar eubiotic bacteria were enriched by the WD and WFMD suggesting ALA and linoleic acid affect the gut microbiome. Enrichment of Lachnospiraceae and associations with improved CVD risk factors suggests the microbiome contributes to the beneficial health effects of walnuts.

Funding Sources: The California Walnut Commission and National Center for Advancing Translational Sciences, NIH.

RevDate: 2019-06-21

Yuan T, Liu Z, X Liu (2019)

The ApoE-dependent Neuroprotective Effects of Sesamol on Diet-induced Obese Mice: The Role of Gut Microbiota and SCFAs (P06-049-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.P06-049-19.

Objectives: Sesamol, an antioxidant lignan from sesame oil, possesses lipid lowering and neuroprotective bioactivities. Considering the distribution of sesamol in gut is much higher than brain after administration, the present work was aimed to elucidate the systemic protective effects of sesamol on dietary-induced cognitive deficits, and to determine the possible link between gut and brain.

Methods: Both wildtype and ApoE-/- mice were fed with high-fat diet (HFD) and treated with sesamol (0.05%, w/v) in drinking water for 10 weeks. The cognitive and anxiety behavioral assessment were evaluated by Morris-water maze, Y-maze, and elevated plus maze tests. The synapse ultrastructure was also detected by transmission electron microscope. Moreover, the alteration of gut microbiome and microbial metabolites short chain fatty acids (SCFAs) were also determined by 16S rDNA sequencing and GC, respectively.

Results: Sesamol prevented HFD-induced bodyweight gain, insulin resistance, and hyperlipidemia. However, the behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype but not ApoE deficient mice. Consistently, sesamol improved synapse ultrastructure and inhibited brain Aβ accumulation in brain in an ApoE-dependent manner. Moreover, sesamol prevented HFD-induced gut barrier damages and systemic inflammation. Sesamol also re-shaped gut microbiome and consequently improved the generation of microbial metabolites short chain fatty acids including acetate, propionate, and butyrate.

Conclusions: To summarized, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and the beneficial effects of sesamol on gut microbiota/metabolites could be translated into metabolic and neurodegenerative diseases treatment.

Funding Sources: This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China.

RevDate: 2019-06-21

Konen O, Peters K, P Tsuji (2019)

A Metagenomic Analysis of the Equine Gut Microbiome with and Without Probiotic Supplementation (P09-006-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz033.P09-006-19.

Objectives: The goal of this study is to compare the microbiome of domesticated horses with and without probiotic supplementation.

Methods: Our University's Institutional Animal Care and Use Committee has granted an exemption, as the horses were not housed on campus and there was no experimental manipulation to the horses' feeding implemented. Fecal matter from six privately owned horses maintained on their standard grazing diet were collected. Three of the six horses received a probiotic supplement, SmartDigest, for several years prior to beginning the project. Supplementation ceased for one month, and samples were again obtained. The other three horses never received probiotics. Bacterial DNA was isolated from all fecal samples, the 16S rRNA gene amplified, tagged with index primers, and subsequently sequenced using the Illumina MiSeq.

Results: Dominant groups from non-supplemented horses residing on the same property included the phyla bacteriodetes, firmicutes, proteobacteria, and verrucomicrobia. Interestingly, Sphingobacterium bambusae was identified in all three horses, even though this species has previously been isolated from the soil of bamboo plantations. Currently, samples from horses with probiotics are being analyzed. We are also employing qPCR analysis to validate the NextGen data, and to further investigate relative abundance of specific bacterial groups relevant to equine intestinal health.

Conclusions: Preliminary NextGen sequence analysis of the relative abundance of bacterial phyla suggests that, as expected, the horses residing on the same property and thus receiving the same diet possess a similar intestinal microbiome composition. Similarities between horses persist down to the genus level, and are now being compared to samples from horses on a probiotic-supplemented diet.

Funding Sources: Financial support was provided by Towson University's Fisher College of Science and Mathematics, and Jess and Mildred Fisher Endowed Chair funds to P. Tsuji.

RevDate: 2019-06-21

Wang M, Smith B, Adams B, et al (2019)

Osteopontin-Enriched Algae Modulates the Gut Microbiota Composition in Weaning Piglets Infected with Enterotoxigenic Escherichia Coli (P06-069-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.P06-069-19.

Objectives: Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in human infants and young farm animals. Osteopontin (OPN), a glycoprotein present in high concentration in human milk, has immunomodulatory functions, which could indirectly impact the microbiota. Furthermore, a previous study has shown fecal microbiota composition differs between wild-type and OPN knockout mice. Herein, the effects of OPN-enriched algae on the gut microbiota composition and volatile fatty acid (VFA) concentrations of ETEC-infected piglets were assessed.

Methods: Naturally-farrowed piglets were sow-reared for 21 days and then randomized to two weaning diets: WT (formula + 1% wild-type algae) or OPN (formula + 1% OPN-enriched algae). On postnatal day (PND) 31, all piglets were infected orally with a live culture of ETEC (1010 colony-forming unit/3 mL dose) daily for three consecutive days. On PND 41, ascending colon (AC) contents were collected. Gut microbiota was assessed by sequencing V3-V4 regions of 16S rRNA gene and VFAs were determined by gas chromatography. Alpha-diversity and VFAs were analyzed using PROC MIXED procedure of SAS. Beta-diversity was evaluated by permutational multivariate analysis of variance (PERMANOVA) and differential abundance analysis on the bacterial genera was performed using DESeq2 package of R.

Results: Shannon indices were lower in the AC contents of OPN piglets compared to WT piglets. The overall colonic microbiota of OPN piglets differed from that of WT piglets (PERMANOVA P = 0.015). At genus level, OPN-enriched algae increased the abundance of Streptococcus, decreased the abundances of Sutterella, Candidatus Soleaferrea, dga-11 gut group, Rikenellaceae RC9 gut group, Ruminococcaceae UCG-010, unculturedRuminococcaceae, Prevotella 2 and 7 compared to piglets consuming wild-type algae (P < 0. 05). OPN piglets also had higher (P < 0.05) concentrations of acetate, propionate, butyrate and valerate compared to WT.

Conclusions: In ETEC infected piglets, 1% OPN-enriched algae decreased alpha-diversity and modulated the microbiota composition and VFA profiles compared to 1% WT algae. Other studies have shown that OPN inhibits biofilm formation in vitro, but future research is needed to assess in vivo microbiome-modulation mechanisms.

Funding Sources: Triton Algae Innovations.

RevDate: 2019-06-21

Collard M, Austin N, Tallant A, et al (2019)

Muscadine Grape Extract Reduces Lung and Liver Metastasis in Mice with Triple Negative Breast Cancer in Association with Changes in the Gut Microbiome (P05-017-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz030.P05-017-19.

Objectives: The goal of this study was to determine if a proprietary muscadine grape seed and skin extract (MGE) inhibits triple negative breast cancer (TNBC) metastasis and alters the gut microbiota.

Methods: 4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control group (n = 8) or a treatment group that received 0.1 mg/mL total phenolics MGE (Piedmont R&D) in the drinking water (n = 8). Mice were sacrificed after 4 weeks; tissues and fecal samples were collected for analysis. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases using the inForm© 2.2 software. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids were detected by gas chromatography (Microbiome Insights). Data are expressed as means ± SEM using student's t-test.

Results: MGE reduced Ki67 cell positivity in the lungs and livers of mice, indicating reduced metastatic proliferation (9.3 ± 0.9% vs 6.2 ± 0.7% and 5.0 ± 1.5% vs 0.77 ± 0.2% cells, respectively; P < 0.01), and decreased cancer associated fibroblasts in the lungs (5.3 ± 1.0% vs 3.0 ± 0.5% cells; P < 0.05), which are associated with metastasis. MGE significantly reduced the number (4.7 ± 0.7 vs 2.2 ± 0.4 tumors/field; P < 0.01) and size (1358 ± 48 vs 1121 ± 47 pixels; P < 0.01) of liver metastases, resulting in decreased metastatic tumor burden (6656 ± 1220 vs 3096 ± 644 total area in pixels; P < 0.01). Attenuated TNBC metastasis correlated with MGE-induced changes in gut microbiota. Alpha diversity (4.15 ± 0.10 vs 4.51 ± 0.13 Shannon index; P < 0.05) and the Firmicutes to Bacteroidetes ratio (0.37 ± 0.07 vs 0.76 ± 0.12; P < 0.05) were significantly increased in MGE-treated mice, indicating enhanced microbial richness and increased energy harvest by the gut microbiome. Butyrate-producing bacteria, such as Ruminococcus, Butyricicoccus and Lachnospiraceae, were increased with MGE (P < 0.05) as well as the anti-inflammatory compound butyrate relative to other short-chain fatty acids (25.0 ± 2.7% vs 75.3 ± 15.5%; P < 0.01).

Conclusions: These data show that MGE attenuates TNBC metastasis in association with alterations in the gut microbiome, suggesting that MGE may be an effective treatment against TNBC metastatic progression.

Funding Sources: Chronic Disease Research Fund.

RevDate: 2019-06-21

Xue H, Chen X, Chen K, et al (2019)

Anthocyanin Improves Glucose Homeostasis in Obese Mice via Beneficial Regulation of Intestinal Microbiota and Barrier Function (OR34-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.OR34-08-19.

Objectives: Anthocyanin (ACN) is a natural polyphenol with anti-diabetic effects. However, intact anthocyanin has low bioavailability and largely arrives unmetabolized in the colon, its mechanisms of action remain unclear. The intestinal microbiota dysbiosis and leaky gut contribute to the development of diet-induced type 2 diabetes. Therefore, we aim to investigate whether the anti-diabetic effects of anthocyanin were related to changes in the gut microbiota and epithelial barrier function.

Methods: Male C57Bl/6 N mice were randomly assigned into 4 groups and pair-fed either a chow or high fat/high sugar diet (HFHS, 45 kcal% fat, 17 kcal% sucrose) +/- 1.0% anthocyanin for 8 weeks. Indices of systemic inflammation, parameters of glucose homeostasis and intestinal barrier function were determined. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with Illumina pyrosequencing. To ascertain the involvement of the gut microbiota in the anti-diabetic effects of anthocyanin. A separate cohort of HFHS-fed C57Bl/6 N mice were oral gavage administered with fecal microbiota from chow-fed donors, HFHS-fed donors, HFHS + ACN-fed donors and heat-killed fecal microbial from HFHS + ACN-fed donors (HK-ACN) for 8 weeks, followed by the same examination.

Results: Relative to vehicle controls, ACN ingestion attenuated several effects of HFHS feeding, including glucose intolerance, insulin resistance and serum inflammatory markers. ACN ingestion reduced intestinal permeability and metabolic endotoxemia. These beneficial effects of ACN were associated with increased expression of genes involved in epithelial barrier function (ZO-1, occludin) and decreased inducible NO-synthase (iNOS) protein levels in ileum and colon of HFHS-fed mice. Gut microbiota analysis revealed that ACN ingestion induced profound alterations in the gut microbiome of HFHS-fed mice. Transplantation of the gut microbiome from ACN-fed mice, but not HFHS-fed or HK-ACN-fed mice, was sufficient to recapitulate the improvement in intestinal epithelial barrier function, systemic inflammation and glucose homeostasis observed with oral ACN treatment.

Conclusions: These findings indicate that ACN-mediated changes in the gut microbiota and epithelial barrier function may play a predominant role in the mechanism of action of anthocyanin.

Funding Sources: The State Key Program of National Natural Science Foundation of China [grant number 81730090].

RevDate: 2019-06-21

Lemas D, Wright L, Francois M, et al (2019)

Recruitment and Retention of Pregnant and Breastfeeding Mothers for Longitudinal Clinical Microbiome Studies (OR30-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.OR30-08-19.

Objectives: Accumulating data suggest the health benefits of breastfeeding are, in part, mediated through interactions with the human microbiome. Despite these observations, recruitment of pregnant mothers in longitudinal clinical microbiome studies remains a significant challenge. The goal of this study is to develop data-driven strategies for recruitment and retention of breastfeeding mothers' into longitudinal clinical microbiome studies.

Methods: We recruited a total of 40 mothers (20 pregnant and 20 breastfeeding) to complete in-depth semi-structured interviews at the UF Clinical and Translational Science Institute. Additionally, mothers were asked to use self-administered microbiome collection kits and complete questionnaires related to health history, infant feeding practices, and physical activity. Informative interviews were designed to identify women's understanding, motivations and barriers surrounding longitudinal clinical research participation and their preferences for providing non-invasive biological samples.

Results: Our preliminary analysis indicates that 1) barriersfor participating in research include convenience, confidentiality and child protection; 2) factors motivating participation in research include general interest in breastfeeding, schedule, and perceived research relevance; 3) participant recruitment should consider social media and 4) biological sample collection should include adequate instructions and drop-off convenience.

Conclusions: The results of this study provide valuable theoretical and practical insights on how to effectively recruit and retain pregnant and breastfeeding women into longitudinal microbiome studies.

Funding Sources: 1K01DK115632-01A1.

RevDate: 2019-06-21

Islam T, Koboziev I, Scoggin S, et al (2019)

Protective Effects of Curcumin in High Fat Diet (HFD)-Induced Obesity Include Anti-Inflammatory Effects in Adipose Tissue and Changes in Gut Microbiome (P06-075-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.P06-075-19.

Objectives: Curcumin, a traditionally used spice in Asia has several health-protecting effects. However, its role on gut microbiota and obesity-associated inflammation is still poorly understood. The objective of this study was to determine whether the protective effects of curcumin in high fat diet (HFD)-induced obesity are mediated by reduced white adipose tissue (WAT) inflammation and changes in gut bacteria.

Methods: Male B6 mice were fed a HFD (45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for thirteen weeks. Body weight, adiposity, glucose and, insulin tolerances, and serum triglycerides, insulin, leptin, resistin levels were measured. Gut microbiome composition was determined by 16S RNA metagenomics sequencing. Expression of inflammation-related genes in WAT was measured by qRT-PCR. Macrophage contents in WAT were evaluated by galectin-3 immunohistochemical staining.

Results: Pro-inflammatory transcription factor nuclear factor NF-kappa-B p65 subunit (p65) and toll-like receptor-4 (TLR-4) gene expression was downregulated in HFC group compared to HFD mice. Furthermore, curcumin reduced total macrophage infiltration in WAT in HFC mice compared to HFD group. Expression of both M1 (CD80, CD38) and M2 (Arginase-1) associated genes was decreased. The relative abundance of bacteria representing the Clostridium genus, which contains numerous short-chain fatty acid (SCFA) producing species, was increased by the curcumin supplement.

Conclusions: Curcumin exerts protective effects in dietary obesity, in part through downregulation of adipose tissue inflammation which may be due to the production of SCFA and, possibly other curcumin metabolites by gut microflora.

Funding Sources: Startup funds and Come N Go award from the College of Human Sciences at Texas Tech University.

RevDate: 2019-06-21

Martinez S, Campa A, Narasimhan G, et al (2019)

Pilot Study on the Effect of Cocaine Use on the Intestinal Microbiome and Metabolome and Inflammation in HIV-Infected Adults in the Miami Adult Studies in HIV (MASH) Cohort (P13-027-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz036.P13-027-19.

Objectives: Drug use disorders play a major role in the HIV epidemic, and survival rates of HIV infected drug users are significantly lower than non-users. Cocaine use, the most prevalent drug of abuse in Miami, Florida, has also been associated with a pro-inflammatory state and recently with imbalances in the intestinal microbiota as compared to cocaine non-use. Cocaine users have higher levels of inflammation, lower Healthy Eating Index scores, and lower food security, which may also reduce the diversity of the dietary intake affecting the exposure to different substrates on the gut microbiota. We hypothesize that the HIV-positive participants who use cocaine will have dysbiosis and that dysbiosis will be associated with food insecurity.

Methods: The MASH cohort will be used as the recruitment source of participants for this study. This is a cross-sectional study that will include covariates such as dietary intake, food security, and sexual behavior that may also affect the intestinal microbiome; current published studies usually do not address these variables. Participants are eligible if they are HIV infected, cocaine users or non-users, 35-66 years old, not diagnosed with HBV or HCV and are not on antibiotic treatment within 3 months of stool sample collection. Stool samples from one bowel movement will be collected using the Norgen Biotek kit and fasting blood plasma used from the MASH reservoir. Microbial DNA will be extracted using the QIAamp DNA Stool Mini Kit and characterization of the intestinal bacterial composition will be completed using 16S rRNA sequencing. Over 200 molecules derived from bacterial metabolism will be available for analysis through non-targeted gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry-based profiling using plasma. Interleukin 6, a measure of inflammation, will be determined using the Quantikine ELISA assay from R&D systems (Minneapolis, MN).

Results: N/A.

Conclusions: Understanding key intestinal bacterial functional pathways that may be altered due to combined impact of cocaine use, HIV infection, and food insecurity will provide a better understanding of the relationships between the host intestinal microbiome and inflammation, and potentially provide novel treatments to improve the health of HIV infected substance users.

Funding Sources: Funded by the National Institute on Drug Abuse, 1U01DA040381-03 and National Institute on Minority Health and Health Disparities, 1U54MD012393-02.

RevDate: 2019-06-21

Shon WJ, Jung MH, Choi EY, et al (2019)

Sugar-sweetened Beverage and High Fat Diet Consumption Harmfully Alters Gut Microbiota and Promotes Gut Inflammation (P20-041-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-041-19.

Objectives: It is clear that epidemiologic trends document a dramatic increasing incidence of inflammatory bowel disease (IBD) paralleling global westernization. Despite strong tie among diets, gut microbiota (GM) and IBD, the exact mechanisms causing IBD remains incompletely understood. Here we hypothesized that changes in the gut immune system, in response to changes in gut microbiome induced "Westernized diet", would be sufficient to trigger IBD.

Methods: We set out to test this hypothesized by analyzing the changes in gut microbiota composition induced by feeding mice with High sugar-solution or/and High fat and demonstrated their causal roles through high-throughput microbiome analyses. We further assessed changes in inflammatory cell recruitment using flow cytometry, and performed transcriptomic profiling analyses of intestine tissue to identify altered gut microbiota deliver changes in intestinal innate immune and adaptive T cell homeostasis. Importantly, to identify the role of the microbiota in directing host immune responses, fecal microbiota transplantation (FMT) experiments were conducted.

Results: The microbiome analyses results showed that Prevotella, Betaproteobacteria, and Cytophaga, which are a well-known the most representative species in IBD, was significantly enriched only in the HF-Sugar group, suggesting that addition of high-sugar to high-fat diet may reshape the GM by favoring colonization of pathobionts. Also, transcriptome and FACS profiling results showed, among others, high sugar synergistically changes intestinal transcriptomic signature related Inflammatory/Immune Response induced by several pro-inflammatory cytokines and induces expansion of inflammatory DCs and T cells driven by the high fat diet. By using FMT, we prove that host immune traits can be regulated by altering the GM.

Conclusions: Together, our large-scale profiling analyses may uncover an interaction between dietary alterations causing IBD and gut microbiota and provide helpful information regarding the microbiota plays a critical role in programming the immune phenotypes of the host.

Funding Sources: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07048023).

RevDate: 2019-06-21

Smith K, Francisco S, Zhu Y, et al (2019)

Gut Microbiota Manipulation in Mice Fed High or Low Glycemic Diets Affects Metabolic and Eye Health (P20-042-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-042-19.

Objectives: We sought to identify the role of gut microbiota in the previously discovered relationship between a high glycemic diet and the development of retinal damage and metabolic health outcomes in aged mice.

Methods: Male C57Bl6/J mice aged 12 months were fed equal amounts of a high glycemic (HG) or low glycemic (LG) diet for 12 months. The compositions of the diets were identical apart from the starch, which was 100% amylopectin in the HG diet and 30% amylopectin/70% amylose in the LG diet.Within each diet, mice were assigned to one of three treatment conditions: antibiotic ablation of gut microbiota (HGabx or LGabx), weekly fecal microbiota transplants (FMT) from donor control mice fed the alternate diet (HG[tLG] or LG[tHG]), or a control group.Mice were weighed weekly and feces and urine were collected at regular intervals for microbiome and metabolome analysis respectively. Mice underwent MRIs to determine body composition, intraperitoneal glucose tolerance tests to determine glycemic responses, and eye fundus imaging and fluorescein angiography to evaluate the health of the retina and retinal vasculature.

Results: Compared with LG-fed controls, the HG-fed controls had significantly increased body fat mass, decreased insulin sensitivity, and an increased prevalence of retinal damage including hypopigmentation and vascular tortuosity.There was no significant difference in body weight between the HGabx and LGabx group throughout the study. The LGabx group had a significantly higher body weight and the HGAbx had significantly lower body weight than their respective control groups throughout the study. The LGabx group had the highest prevalence of abnormal retinal findings. Survival was significantly decreased in the HGabx mice compared with mice of all other groups of mice, and most died suddenly and presented with an enlarged and hemorrhagic cecum.There was no significant effect of the FMT on body weight or body composition compared with the control mice. The HG[tLG] group had improved insulin sensitivity relative to the HG controls.

Conclusions: Gut microbiota mediate the relationship between the glycemic response to the diet and health outcomes such as obesity, insulin sensitivity, eye health, and survival.

Funding Sources: BrightFocus Foundation, USDA/NIFA AFRI grant 2015-05470, USDA contract 1950-510000-060-03A from ARS, Stanley N. Gershoff Scholarship.

RevDate: 2019-06-21

Antony J, Iyer J, Guthrie N, et al (2019)

The Supremacy of Aggregated N-of-1 Trials for Evidence-based Nutrition Studies (P06-096-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.P06-096-19.

Objectives: Design of aggregated N-of-1 trials with the intent of identifying individuals' unique response to probiotics by studying each individual directly. Consideration of their biochemical uniqueness will ensure sufficient data are collected on each individual to make unequivocal claims on their responses to probiotics.

Methods: In the aggregate N-of-1 trial design, measurements taken will encompass multivariate outcomes including monitoring weight, microbiome species abundance in total fecal DNA for quantitative metagenomics to evaluate microbial gene richness and quantification of short chain fatty acids; influence of probiotics on mood, cognition, depression and sleep may be measured using wireless devices.

Results: A pragmatic analysis approach will provide information beyond significant differences in outcomes from baseline, as well, identifying variation around outcomes for the individual. Decreasing variation over time would suggest a more stable state for a particular outcome. Data from a series of sophisticated N-of-1 studies will, therefore, provide a scientifically sound basis for the creation of a global index detailing the relationship between a nutritional response and genetic features, biochemical, behavioural and exposure levels. Physicians and health care providers can leverage this data to decide on how to manage a patient's condition, while nutraceutical companies can make more specific claims for their products.

Conclusions: N-of-1 trials are a logical extension to clinical practice as physicians deal with patients as individuals with unique characteristics and treatment algorithms in a traditional clinical care setting using patient outcomes to decide if the intervention worked. N-of-1 trials and aggregated N-of-1 trials help identify factors that influence responses to nutrition that may be shared among individuals. Results from N-of-1 trials may be effectively used in Augmented Randomized double-blind Clinical Trial design to identify responders with a goal in formulating successful probiotic interventions.

Funding Sources: KGK Science Inc.

RevDate: 2019-06-21

Young W, Carco C, Mullaney J, et al (2019)

The Microbiome in Functional Gastrointestinal Disorders Is Characterized by Bacteria and Genes Involved in Carbohydrate and Bile Acid Metabolism (OR23-01-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR23-01-19.

Objectives: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal (GI) disorder featuring chronic or recurrent abdominal discomfort, usually with changes in GI habit. To improve our understanding of links between the microbiome and IBS, and how these links can be manipulated through diet, we undertook shotgun metagenomic sequencing of fecal samples from a case-control study.

Methods: Fecal samples from 172 individuals were analyzed by shotgun sequencing using the Illumina NextSeq platform. Of these, 77 were classified as controls, 16 were constipation-predominant IBS (IBS-C), 39 were diarrhea-predominant IBS (IBS-D), 29 were diagnosed with functional constipation (FC), and 11 had functional diarrhea (FD). Taxonomic classifications were determined using Metaxa2 and the SILVA 128 database. Gene functions were assigned by alignment of sequences against a protein reference database using DIAMOND. Mean relative abundance of bacterial taxa and functional genes were compared using permutation ANOVA. Ethical approval was obtained from the University of Otago Human Ethics Committee (Health) (Reference H16/094).

Results: Bacterial genera that discriminated case-controls (P < 0.05) from those with constipation (IBS-C + FC) and diarrhea (IBS-D + FD) included Megasphaera (increased in those with constipation), Blautia (increased in those with diarrhea), and Bilophila (increased in both constipation and diarrhea groups). Megasphaera and Blautia include bacteria that are bile-resistant and produce butyrate, possessing a wide range of Carbohydrate-Active enzymes. Bilophila are sulfite-reducing bacteria that are able to utilize bile-acids. Associated with these taxonomic differences, a wide range of genes involved in carbohydrate, energy, and amino acid metabolism differed significantly (P < 0.05), including some involved in taurine and glycine metabolism. Bile acids are conjugated with taurine or glycine in the liver, and these amino acids are removed by the action of members of the GI microbiota.

Conclusions: Results from our study suggest carbohydrate and bile acid metabolism by the GI microbiome may be important distinguishing characteristics in functional GI disorders.

Funding Sources: Funded by the New Zealand National Science Challenge High-Value Nutrition program.

RevDate: 2019-06-21

Roy CL, Bowyer R, Steves C, et al (2019)

Dissecting the Role of the Gut Microbiota and Diet on Visceral Fat Mass Accumulation (OR31-07-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz037.OR31-07-19.

Objectives: Accumulation of visceral fat mass (VFM) is a major risk factor for cardiovascular and metabolic disease. Both gut microbiota and diet have been shown to impact host adiposity in an interdependent manner, but the exact nature of their joint contributions has not been characterised. Here, we aimed to estimate and separate the effect of gut microbiota composition from that of nutrient intake on host VFM in of 1760 older female twins.

Methods: The gut microbiome profile was assessed by 16S sequencing. VFM was measured by DEXA whole body scan and nutrient intake was assessed through food frequency questionnaires. We used a combination of pair-wise associations, random forest modelling and mediation analysis to separate the effect of the gut microbiota and nutrients on VFM.

Results: Pairwise analyses revealed that 93 OTUs and 10 nutrients were significantly linked to VFM. Five of the 10 nutrients (fibre, trans fatty acids, magnesium, vitamin E and biotin) were also associated with 23% of the 93 VFM-associated OTUs. To separate the effects of the gut microbiota from nutrients on VFM we carried out conditional analyses. We observed that the majority (87%) of the 93 OTUs remained significantly associated with VFM irrespective of nutrient intake correction. In contrast, we observed that fibre, magnesium, biotin and vitamin E were no longer significantly associated with VFM when adjusting models for OTUs (P > 0.05), implying a role of the gut microbiota in mediating these nutrient effects on VFM. Formal mediation analysis revealed that the individual effect of fibre, biotin, magnesium and vitamin E on VFM were mediated at 69, 43, 41 and 31% respectively by OTUs. Moreover, we estimated that accumulated effect of OTUs on VFM (R2 = 0.19) was twice the one of nutrients (R2 = 0.11) and so were their prediction potential determined using random forest classification.

Conclusions: Our results suggest that while the role of certain nutrients on VFM appears to depend on gut microbiota composition, specific gut microbes may affect host adiposity regardless of dietary intake. The findings imply that the gut microbiota may have a greater contribution towards shaping host adiposity and VFM, compared to diet alone.

Funding Sources: We gratefully acknowledge support provided by the JPI HDHL funded DINAMIC consortium (administered by the MRC UK, MR/N030125/1).

RevDate: 2019-06-21

Kok CR, Brabec B, Chichlowski M, et al (2019)

Stool Microbiota in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (FS04-07-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.FS04-07-19.

Objectives: Infant feeding practices play a central role in development of gut microbiome and community structure. Our goal was to test the hypothesis that diets with intact or extensively hydrolyzed proteins or free amino acids may differentially affect the intestinal microbiota composition and immune reactivity.

Methods: This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota outcomes from Baseline (1-7 days of age) up to 60 days of age in healthy term infants. Infants received mother's own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: amino-acid based (AAF; n = 25) or extensively hydrolyzed cow's milk protein (EHF; n = 28). Neither study formula included added Lactobacillus rhamnosus GG. DNA was extracted (Baseline, Day 30, Day 60), 16S rRNA genes were amplified and sequenced (Illumina MiSeq), and exact amplicon sequence variants (ASV) were assigned using the DADA2 model. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis distance) and differential abundance in taxa were analyzed. Relative ASV enrichment (Baseline vs Day 60) was visualized using heat maps and taxa abundance was analyzed by DESEq2 in R (ver 3.4.3).

Results: Complete stool data (all study time points) were available for 49 participants. Baseline alpha diversity measures were similar among groups. The HM group remained stable throughout the study. However, alpha diversity measures by Day 60 were significantly higher for AAF and EHF groups compared to HM. Significant group differences in beta diversity at Day 60 were detected (P < 0.001); AAF and EHF clustered more closely compared to the HM group. Relative Bifidobacterium abundance increased over time and was significantly enriched at Day 60 in the HM group (Figure, A). At Day 60, a significant increase in members of Firmicutes was detected for AAF and EHF groups; a decrease in Enterobacteriaceae (Escherichia) was observed for EHF (Figure, B).

Conclusions: Distinct patterns of early neonatal microbiome establishment were demonstrated for infants receiving mother's own milk compared to amino acid-based or extensively hydrolyzed protein infant formulas. Providing different sources of dietary protein early in life may impact gut microbiome development.

Funding Sources: Mead Johnson Pediatric Nutrition Institute.

RevDate: 2019-06-21

van der Merwe M, Sharma S, Caldwell J, et al (2019)

Timed Feeding Protocols While Consuming a High Fat Diet Do Not Alter Gut Fungal Populations (OR23-06-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR23-06-19.

Objectives: The gut microbiome participates in host metabolic regulation. While the vast majority of microbiome research has focused on bacterial populations, other microorganisms also colonize the mammalian intestine and likely play functionally important roles in host metabolism. The objective of current study was to characterize the role of dietary composition and timing strategies upon gut fungal populations.

Methods: C57BL/6 male mice were randomized to a Chow diet or a high-fat diet (HFD) for 6 weeks, followed by a switch from HFD to 1) Chow (sChow), 2) Purified High Fiber - Daniel Fast (DF), 3) HFD ad lib, 4) HFD time restricted (TRF), 5) HFD alternative day fasting (ADF), or 6) HFD 60% caloric restriction (CR) for an additional 8 weeks. Ileal, cecal and serial fecal samples were collected for next generation sequencing of ITS2 rRNA to examine the gut mycobiome.

Results: We observed dramatic reductions in alpha diversity in fecal fungal populations when animals consumed the HFD compared with Chow. HFD resulted in dramatic reduction in the relative abundance of the fungal order Saccharomyces, with a concomitant increases in the genus Candida and Hanseniaspora. In response to dietary switch from HFD to Chow, fungal taxonomic composition, alpha, and beta diversity transitioned to a population clustering more similarity with Chow by weeks 4 and 8 of intervention. After 8 weeks on the respective dietary interventions, alpha diversity of the ileal, cecal and fecal fungal population in mice consuming DF or various HFD fasting protocols remained similar to the HFD controls. Saccharomycetales remained the dominant genus present in HFD and DF groups. However, amongst these groups, the DF group (fecal sample) showed the greatest increase in Saccharomyces, but time-restricted feeding protocols also showed increased levels of Saccharomyces.

Conclusions: While fasting protocols on HFD are associated with improved metabolic outcomes, these data demonstrate that - similar to microbial populations within the microbiome - diet remains the largest driver of microorganism community composition. To our knowledge, this is the first investigation into the role of dietary timing strategies upon the gut fungal communities ever reported.

Funding Sources: University of Memphis. Children's Foundation Research Institute, Memphis.

RevDate: 2019-06-21

Fritsch D, Wernimont S, Jackson M, et al (2019)

Select Dietary Fibers Alter GI Microbiome Composition & Promote Fermentative Metabolism in the Lower Gastrointestinal Tract of Healthy Adult Dogs (P20-044-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-044-19.

Objectives: The canine gastrointestinal (GI) microbiome is capable of fermenting fibers. We evaluated select dietary plant fibers on canine GI microbiome composition & metabolism.

Methods: 39 adult dogs were fed a control food (CF) for 4 weeks, then fed a test food (TF) for 4 weeks. (CF: 3411 kcals/kg, 2.2 g total dietary fiber, TDF; 0.5 g soluble fiber, SF; 1.7 g insoluble fiber, INSF per 100 kcal; TF: 3273 kcal/kg, 5.0 g TDF, 0.8 g SF, 4.2 g INSF per 100 kcal). Foods were complete & balanced dry foods & met 2017 AAFCO nutritional guidelines. CF fiber sources: cracked pearled barley, whole corn, whole grain oats, cellulose; TF: cracked pearled barley, whole corn, whole grain oats, ground pecan shells, cellulose, flaxseed, dried beet pulp, dried citrus pulp, pressed cranberries, dried pumpkin, psyllium seed husks, & ginger root. Feces were collected after 4 weeks of feeding CF and TF, homogenized, & frozen at -80C within 1 hour of defecation. Fecal microbiome 16 s rRNA sequencing was performed using Illumina MiSeq and processed through Mothur. Predicted microbial functions were determined by PICRUSt and analyzed using PERMANOVA. Count-normalized data were CLR transformed & analyzed using negative binomial mixed models. Fecal short chain fatty acids (SCFA) were analyzed using liquid-liquid extraction & gas chromatography with flame ionization detection. Results significant at P < 0.05 are reported. The study was reviewed & approved by the Institutional Animal Care & Use Committee, Hill's Pet Nutrition, Inc. Dogs had access to clean fresh water at all times.

Results: TF significantly increased fecal acetic acid, decreased putrefactive metabolites such as isobutyric, 2-methylbutyric, & isovaleric acids. The acetate-& lactate-producing genera Bacteroides and Faecalibacterium were significantly increased while Streptococus and Enterococcus were significantly decreased vs CF. Predicted microbial functions representing butyrate, phenylalanine & tyrosine metabolic pathways were significantly different from CF.

Conclusions: TF shifts canine GI microbiome composition and metabolism toward saccharolytic fermentation & decreases putrefactive metabolites, characteristics which provide beneficial impacts to canine GI health.

Funding Sources: This study was funded by Hill's Pet Nutrition, Inc.

RevDate: 2019-06-21

Liu Z, Yuan T, Dai X, et al (2019)

Intermittent Fasting Alleviates Diabetes-induced Cognitive Decline via Gut Microbiota-metabolites-brain Axis (OR32-04-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz052.OR32-04-19.

Objectives: Cognitive decline is one of severe type 2 diabetes complications. Intermittent fasting (IF) is a promising dietary intervention for T2D risk reduction, but its protective effect and mechanism on diabetic cognitive dysfunction remain elusive. Gut microbiota plays a vital role interphasing diet and host physiology and pathology and highly affected by the dietary composition and patterns. It has been reported that the microbiota homeostasis is essential for maintenance of gut health and for modulating cognitive function. We hypothesized that gut microbiota might play a pivotal role in mediating protective effects of IF on diabetes-induced cognitive decline.

Methods: After a 28-day IF regimen treatment, cognitive behavioral tests and brain insulin signaling were assessed on db/db mice. The microbiota-metabolites-brain axis alterations were detected by multiple-omics analysis (transciptomics, 16S rRNA sequencing and metabolomics). A intergrade multi-omics analysis was performed to analyze the correlation among gut microbiota, plasma metabolites, and hippocampal gene expression.

Results: Here we found that a 28-day Intermittent fasting (IF) regimen improved cognitive deficits in db/db mice via a microbiota-metabolites-brain axis assessed by behavioral tests and multiple-omics analysis: IF activated AMPK/PGC1α signaling, enhanced mitochondrial biogenesis in hippocampus and elevated genes enriched in hippocampal metabolic function. Moreover, IF re-structured gut microbiota and improved plasma microbial metabolites in relation to diabetes and cognitive function, e.g., serotonin, 3-Indolepropionic acid, and bile acids. Integration of multi-omics data demonstrated strong links between IF-related genes, gut microbiome and metabolites. Furthermore, removal of gut microbiota with antibiotics partly abolished the observed benefits of IF on cognition and hippocampal metabolic function.

Conclusions: Taken together, the present study suggests a critical role of gut microbiota in connecting peripheral metabolism with brain function, which could lead to novel interventions against metabolism-implicated neurodegenerative pathophysiologies.

Funding Sources: This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China.

RevDate: 2019-06-21

Fraser K, Young W, McNabb W, et al (2019)

Lipid and Metabolite Profiles in Human Plasma and Associations with the Microbiome and Functional Gastrointestinal Disorders (P20-033-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-033-19.

Objectives: Metabolomic profiling of plasma provides a biochemical fingerprint of the circulating metabolites from the host and microbiome, and may assist with understanding mechanisms underlying functional gastrointestinal (GI) disorders such as Irritable Bowel Syndrome (IBS). In a case-control study, we aimed to identify microbial and host factors in plasma to provide mechanistic insights into functional GI disorders and increase the predictability of phenotypes for use in nutrition intervention studies.

Methods: Plasma samples from 246 individuals with functional GI disorders (cases) or asymptomatic (controls), consisting of 93 healthy controls, 54 with functional constipation (C) or IBS-C, 60 with functional diarrhoea (D) or IBS-D, and 39 diagnosed as IBS-mixed or awaiting diagnosis. Plasma was subjected to biphasic extraction and global metabolite profiling was performed using three separate untargeted liquid chromatography high resolution mass spectrometry analysis (LC-MS) methods (polar, semi-polar and non-polar chromatography).

Results: Plasma metabolomic profiles differed considerably between the IBS phenotypes and those of the control subjects. Multivariate partial least squares discriminant analysis of 428 annotated lipid species highlighted significant differences (P < 0.001) between IBS-C and healthy control subjects. Univariate analysis revealed significant differences in the concentrations of 48 lipid species (P < 0.05) between the two groups, including elevated concentrations of many sphingolipids and phospholipids in the IBS-C group. Biochemical network analysis also revealed major perturbations in amino acid, bile acid and lipid metabolism, and highlighted key metabolic pathways included microbial related pathways.

Conclusions: Perturbations of plasma lipid concentrations in the IBS subjects suggest changes may occur with both host and microbial lipid metabolism. Future efforts to investigate these links will utilize a systems biology approach integrating metabolomic and fecal metagenomic datasets to further identify key pathways and biomarkers that characterize functional GI disorders and how nutrition can improve GI health and function.

Funding Sources: Funded by the New Zealand National Science Challenge High-Value Nutrition program.

RevDate: 2019-06-21

Piccolo B, Krishnan S, Shankar K, et al (2019)

An 8-week Controlled Feeding Trial Based on the 2010 Dietary Guidelines for Americans Has Minimal Effect on the Fecal Microbiota in Overweight and Obese Women (FS11-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz037.FS11-08-19.

Objectives: To determine whether a high quality diet based on the 2010 Dietary Guidelines of America (DGA) alters the composition of the fecal microbiome in individuals at risk for cardiometabolic disease, compared to a diet based on a typical American diet (TAD).

Methods: A total of 52 overweight and obese women were enrolled in a randomized, double-blind, controlled feeding trial. Women were randomly assigned to the DGA or TAD group (n = 28 DGA and 24 TAD). Diets matched each participant's estimated energy requirement and subjects remained weight-stable. The DGA diet was based on the 2010 DGA food-group recommendations, whereas the TAD diet was based on the average adult intake patterns from the NHANES 2009-2010 survey. Participants provided a stool sample 1-week prior to intervention (W0), within the second week of diet intervention (W2), and at the final week of intervention (W8). Microbial profiles were assessed using 16S rRNA amplicon sequencing and expressed as median % relative abundance. Data analyses were performed using standardized pipelines (QIIME 1.9 and R packages). False Discovery Rate (FDR) was set at 0.2.

Results: No differences were found in α- and β-diversity indices at the operational taxomonic unit (OTU) level by diet assignment at W0, and no taxa were differentially abundant at FDR < 0.2. Similarly, α- and β-diversity indices (OTU level) were not altered by diet within W2 or W8. A single OTU within the Ruminococcus genera was higher in TAD at both W2 (TAD = 0.014%; DGA = 0.00%) and W8 (TAD = 0.017%; DGA = 0.00%; FDR < 0.05), and the Adlercreutzia genera from the Actinobacteria phyla was also higher in TAD at both W2 (TAD = 0.027%; DGA = 0.001%) and W8 (TAD = 0.022%; DGA = 0.002%). No within-diet differences between W0 and W2, and W0 and W8 were observed in any α- and β-diversity indices tested. When adjusting for W0 relative abundances, 10 OTUs were altered by diet at W2 and 39 OTUs were altered at W8.

Conclusions: A weight-maintaining diet based on the 2010 DGA minimally differed in the fecal microbiota compared to a weight-maintaining typical American diet. Results herein suggests differences in food-based dietary patterns does not have a large effect on the composition of the fecal microbiota in humans.

Funding Sources: Supported by National Dairy Council; Campbell Soup Co.; USDA-ARS Projects 2032-51530-022-00D and 6026-51000-010-05S.

RevDate: 2019-06-21

Faramarzi S, K Krishnan (2019)

The Spectacular Role of the Human Microbiome in Preventing Post-prandial or Metabolic Endotoxemia (OR23-02-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR23-02-19.

Objectives: To determine if 30-d of oral spore-based probiotic supplementation could reduce dietary endotoxemia.

Methods: Apparently healthy men and women (n = 75) were screened for post-prandial dietary endotoxemia. Subjects whose serum endotoxin concentration increased by at least 5-fold from pre-meal levels at 5-h post-prandial were considered "responders" and were randomized to receive either placebo (rice flour) or a commercial spore-based probiotic supplement [Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans, and Bacillus licheniformis, and Bacillus clausii] for 30-d. The dietary endotoxemia test was repeated at the conclusion of the supplementation period. Dietary endotoxin (LAL) and triglycerides (enzymatic) were measured using an automated chemistry analyzer. Serum disease risk biomarkers were measured using bead-based multiplex assays (Luminex and Milliplex) as secondary, exploratory measures.

Results: Data were statistically analyzed using repeated measures ANOVA and a P < 0.05. We found that spore-based probiotic supplementation was associated with a 42% reduction in endotoxin (12.9 ± 3.5 vs 6.1 ± 2.6, P = 0.011) and 24% reduction in triglyceride (212 ± 28 vs 138 ± 12, P = 0.004) in the post-prandial period Placebo subjects presented with a 36% increase in endotoxin (10.3 ± 3.4 vs 15.4 ± 4.1, P = 0.011) and 5% decrease in triglycerides (191 ± 24 vs 186 ± 28, P = 0.004) over the same post-prandial period. We also found that spore-based probiotic supplementation was associated with significant post-prandial reductions in IL-12p70 (24.3 ± 2.2 vs 21.5 ± 1.7, P = 0.017) and IL-1β (1.9 ± 0.2 vs 1.6 ± 0.1, P = 0.020). Compared to placebo post supplementation, probiotic subject had less ghrelin (6.8 ± 0.4 vs 8.3 ± 1.1, P = 0.017) compared to placebo subjects.

Conclusions: 30 days of supplementation with spore-based probiotics showed a 60% reduction in biomarkers of leaky gut when compared to the placebo group. These findings suggest that probiotics may play an integral role in reducing chronic low-grade inflammation that leads to chronic disease and autoimmunity.

Funding Sources: The present study was funded in part by a competitive research grant from Microbiome Labs, LLC (Glenview, IL) to the University of North Texas.

RevDate: 2019-06-21

Cresci G, B Glueck (2019)

The Role of Bacteriocin Producing Probiotic in Clostridium Difficile Colonization in Mice (P20-010-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-010-19.

Objectives: To test the efficacy of a spore-forming, bacteriocin-producing probiotic in mitigating intestinal Clostridium difficile colonization and injury in mice.

Methods: 10-12 week old female CF1 mice were treated with clindamycin for 3 days, followed by Clostridium difficile exposure (5log10 CFU). Stool samples were collected at baseline, following clindamycin treatment, and 1,3 and 5 days after C. difficile exposure. A separate group of mice were also supplemented with a bacteriocin/spore forming probiotic throughout the study period. Five days after C. difficile exposure mice were euthanized and intestine was dissected and the length was measured and then used to prepare RNA, protein lysate, histology, and cecum contents were analyzed for bacterial colonization.

Results: All mice exposed to clindamycin had overgrowth of enterococcus and gram negative bacteria and those exposed to C. difficile spores were positive for C. difficile colonization one day after exposure. Of interest, the probiotic supplemented mice resolved the overgrowth of enterococcus and gram negative bacteria as well as C. difficile colonization quicker than the saline treated group. The intestinal length was higher and cecum: body weight was lower in the probiotic supplemented mice compared to those treated with saline. These findings were associated with decreased mRNA expression of inflammatory cytokines and increased anti-inflammatory cytokines in the intestine.

Conclusions: A bacteriocin-producing probiotic accelerated resolution of bacterial overgrowth and C. difficile colonization and preserved mouse intestinal integrity during antibiotic-induced C. difficile colonization. These data suggest supplementation with a bacteriocin-producing probiotic may serve as a potential protective therapy during antibiotic exposure.

Funding Sources: Microbiome Labs.

RevDate: 2019-06-21

Spector T, Berry S, Valdes A, et al (2019)

Integrating Metagenomic Information into Personalized Nutrition Tools: The PREDICT I Study (P20-005-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-005-19.

Objectives: The existence of a link between the intestinal microbiome and diet is well established. The demonstration that the microbiome information increases the prediction accuracy of postprandial blood glucose levels (Zeevi et al, 2015) is opening intriguing perspectives for developing personalized nutrition tools. However, reproducibly inferring the diet-induced microbiome changes and stratifying individual responses to dietary interventions based on the microbiome remain open challenges. The PREDICT I study aims to develop: (i) a protocol for gut microbiome sampling and analysis for large-scale nutritional studies and (ii) a microbiome-based machine learning integrative component for predictive personalized nutrition tools.

Methods: We performed three metagenomic investigations to; (i) identify the best combination for stool collection, sample storage, DNA extraction, and sequencing (n = 45); (ii) develop and validate the computational pipeline on an exploratory dietary interventional cohort (n = 1000); (iii) apply the validated pipeline on an independent validation cohort (n = 100). The generated total dataset (>8x10^12 sequenced bases) was analyzed with existing and newly developed computational tools and integrated with the metagenomic profiles of >10,000 samples processed from public repositories.

Results: Our resulting validated protocol involves a minimally time-demanding procedure for at-home sample collection, sample storage in a preservation buffer, and DNA extraction with a recently commercialized kit (Qiagen). Metagenomic sequencing proved substantially more accurate than 16S rRNA sequencing and was able to perfectly capture subject-specific strain-level features with longitudinal sampling. This method was also able to stratify by pre-intervention habitual dietary regimes. Our prediction algorithm showed that embedding the microbiome features in a 50-dimension space was sufficient to improve the prediction performance of postprandial blood glucose levels.

Conclusions: We present the largest investigation to date on the reproducible connections between the gut microbiome and dietary interventions. Further we describe our methods and results in using the microbiome as a component of a precise integrated postprandial blood glucose and blood lipid level predictor.

Funding Sources: Zoe Global Limited, National Institute for Health Research (NIHR), Wellcome Trust.

RevDate: 2019-06-21

Webb K, Peterson J, Fox S, et al (2019)

Effect of Prebiotic, Probiotic, and Enzyme Supplementation on Gut Fermentation, Markers of Inflammation and Immune Response in Individuals with GI Symptoms (P20-024-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-024-19.

Objectives: Chronic gastrointestinal distress (GID) effects up to 33.8% of people and results in over 15 million outpatient visits in the US annually. Currently, probiotic and prebiotic supplements are recommended by physicians, dietitians, and other healthcare providers to normalize GI function and to mitigate symptoms associated with certain disease states. GlutenShield (GS) is a commercially available nutritional supplement designed to contain an appropriate balance of pre- and probiotics as well as digestive enzymes to improve symptoms associated with GID. The aim of this study was to determine the tolerance to and/or benefits of GS supplementation on adults with GID.

Methods: This was a partially blinded pilot study in which all subjects completed a 2-week washout and were then randomized to receive GS or the placebo 3 times/day with meals. Participants completed a pre-treatment FFQ as well as a pre- and post-treatment GID questionnaire, POMS questionnaire, blood draw, and stool sample.

Results: No differences between placebo and treatment groups were found for serum inflammatory cytokines or fecal volatile fatty acids (area % or concentration) (P > 0.05). A significant reduction in IgG2 was observed in the GS group (7110.4 vs 4185.56; P = 0.008) as well as a significant reduction in self-reported bloating (P = 0.038) and approaching significant reduction in total GID (P = 0.083). Fecal insoluble dietary fiber (IDF) percentage significantly increased in the placebo group (P = 0.012), with no change in the GS group (P > 0.05).

Conclusions: Research findings suggest that GS was well tolerated and perceived to be beneficial compared to placebo; however, further research is needed to identify the specific patient population of GID patients who could most benefit from GS supplementation. Future analysis of microbiome data of subjects could provide additional insight. Clinical trial ID: NCT03403387.

Funding Sources: ETSU (CCRHS, Dean's Research Enhancement Award and CPH, Health Sciences Funding) and Shield Nutraceuticals, LLC.

RevDate: 2019-06-21

Ojo B, Gallucci G, Ritchey J, et al (2019)

Pinto Beans Supplementation Impacted the Gut Microbiome, Inflammation, MHC II Expression and Glucose Homeostasis in C57BL/6 J Mice Regardless of Dietary Fat Content (P21-028-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz041.P21-028-19.

Objectives: Fiber-rich foods such as pinto beans (PB) may exhibit prebiotic effects by preventing early immunosuppression and gut permeability associated with the onset of insulin resistance (IR). Thus, this study evaluated the early protective effects of PB supplementation on the cecal gut microflora, tight-junction protein abundances, gut inflammatory markers and glucose homeostasis in mice fed either a control (C) or a high-fat, high sucrose (HFS).

Methods: Six-wk-old, male C57BL/6 J mice were randomly assigned to four groups (n = 12/group) and fed a control (C, 10% kcal fat, 10% kcal sucrose) or HFS (45% kcal fat, 20% kcal sucrose) diet with or without 10% (wt/wt) freeze-dried PB for 30 d. Measures include fasting blood glucose (FBG), cecal bacteria analyses by 16 S rDNA sequencing, gene expression of gut antimicrobial peptides and markers of inflammation in the distal ileum by qPCR, and expression of tight junction proteins, STAT3 and MHC II in the distal ileum by immunoblotting. Statistical analyses include the Kruskal-Wallis/Dunn's post-hoc test, and a 2-way ANOVA using factors of HFS and PB.

Results: FBG was increased by HFS (main effect, P = 0.0070) while PB decreased FBG by at least 13% (main effect, P = 0.046). In the cecum, the sulfide-producing bacteria family Desulfovibrionaceae (genus Bilophilia) was decreased (≤49%, P ≤ 0.022) in the PB-fed mice compared to their controls. In contrast, the short chain fatty acid-producing family Lachnospiraceae, was elevated by at least 47% (P ≤ 0.0043) in the PB-fed groups compared to their controls. We also observed a 3-fold decrease (P = 0.012) in Ifng gene expression in the HFS group compared to control, together with a decrease in the phosphorylation of STAT3 in the distal ileum (P = 0.045). On the other hand, PB supplementation increased pSTAT3 (main effect, P = 0.022), MHC II (≥66%, main effect, P = 0.0040), with a trend to upregulate occludin (P = 0.055). Moreover, antimicrobial peptide genes, Reg3β and Reg3γ, and Il10 were upregulated by PB (main effect, P < 0.0094). Finally, a negative correlation between the genus Bilophilia and MHC II (Spearman, ρ = -0.5747, P = 0.0033) was observed.

Conclusions: PB supplementation modulated the gut microbiome regardless of dietary fat content, and upregulated MHC II in the distal ileum. These effects may be central to its potential to protect against diet-induced IR.

Funding Sources: Northarvest Bean Growers Association.

RevDate: 2019-06-21

Shay N, Sturm M, Becraft A, et al (2019)

Glucose Metabolism and Cecal Microbiome Populations Are Improved and Hepatic Biochemical Levels Altered with Consumption of Grape Powder by High-fat Fed C57BL/6 J Mice (P06-024-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.P06-024-19.

Objectives: Grapes are nutrient-dense, particularly in polyphenolic compounds. Previous research demonstrates benefits of whole grape and grape skin, seed, and polyphenol intake on glucose homeostasis along with other health benefits. We tested the hypothesis that intake of 4 servings per day of table grape would remediate metabolic complications in C57BL/6 J (C57) male mice fed a high-fat diet with added cholesterol and fructose diet modeling an obesogenic and diabetogenic western-style diet.

Methods: Groups of mice (n = 12) were provided either low-fat plus placebo diet (LF, 10% kcal fat), high-fat plus placebo (HF, 45% kcal fat), or HF plus grape powder (HF + G), for 8 weeks. Grape powder was provided at ∼10% of total energy of diet. C57 mice were provided experimental diets ad libitum. Body weights, food intake, and glucose tolerance were determined. Postmortem, inflammatory markers, cecal microbiome, and the relative concentrations of hepatic metabolites were determined.

Results: Fasting blood glucose was reduced in the HF + G group compared to HF-fed mice. The glucose tolerance test demonstrated that the Area Under the Curve (AUC) was also reduced. Further, a significant decrease in circulating levels of insulin were observed with HF + G supplementation. The cecal microbiome from HF + G fed mice overlapped with both the HF and LF controls, but also had characteristic shifts that were unique to grape powder consumption. Metabolomic analysis indicated grape consumption impacted inflammation and β-oxidation biomarkers indicating some remediation of hepatic pathologies associated with HF food consumption. The most significantly different hepatic metabolites included grape-derived S-methymethionine and trigonelline, while other murine hepatic metabolites significantly regulated by diet included myo-inositol and 15-HETE.

Conclusions: Table grape supplementation with a HF western-style diet significantly improved fasting blood glucose, circulating insulin concentrations, and HOMA-IR in C576J/Bl male mice. demonstrating an anti-diabetic effect of grape powder. At modest level of supplementation equivalent to 4 servings/day, grape powder also improved microbiome composition and changed relative levels of specific hepatic metabolites. Up-regulation of 15-HETE by diet suggests grape powder consumption may enhance PPARγ-directed gene expression, consistent with increases in glucose sensitivity observed in this study.

Funding Sources: California Table Grape Commission.

RevDate: 2019-06-21

Kerver J, Gryc J, Shanahan M, et al (2019)

Feasibility of a Diet Intervention Trial During Pregnancy in a Rural Population: The PEAPOD Pilot Study (P11-013-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.P11-013-19.

Objectives: Healthy pregnancy diet is important for infant development, but maternal dietary effects on establishment of the infant gut microbiome are not well understood. Our goal was to test the feasibility of conducting a randomized controlled trial (RCT) to implement a diet intervention and collect survey data and biospecimens from pregnant women and their infants.

Methods: Employing a 2-arm RCT, we recruited women (n = 27) in mid-pregnancy from a prenatal care clinic, randomized participants to the intervention (n = 13) or to usual care (n = 14), and followed to 6 wks postpartum. Data collection included surveys, maternal blood, urine, and stool at three time points (T1 = 25 and T2 = 36 wks gestation [pre- and 4 wks post-intervention initiation, respectively]; T3 = 6 wks postpartum), and infant stool at 6 wks. The intervention was initiated at 32 wks gestation and continued until birth of the baby. In wk 1, participants received non-perishable high fiber foods (whole wheat cereal, oatmeal, dried fruit, canned beans) as well as olive oil, vinegar, recipes for salad dressing and side dishes, and general nutrition information. Partnering with a hospital catering service, the intervention included weekly food delivery of 3 large prepared salads, 2 quarts of soup including either legumes or whole grains (e.g., beans, barley), and 5 pieces of fresh fruit (e.g., apples, oranges).

Results: Our sample is considered entirely rural and maternal characteristics reflected the local population: 100% White, 17% Hispanic or Native American; 89% at least some college; 26% Medicaid; 33% ever smoked. Mean maternal age was 29.6 y (range 20-40 y), mean pre-pregnancy BMI was 26.9 kg/m2 (range 18.5-41.6). Data collection adherence was high with few missing data points: T1 = 100% for survey, blood, urine, stool; T2 = 93% for stool, 96% for blood and urine; T3 = 93% for survey, blood, urine, and stool). Overall satisfaction was high with 85% reporting satisfied or very satisfied and important qualitative insights were gained from participants.

Conclusions: This pilot trial produced valuable information to effectively refine the intervention so that it can be tested in a larger, longer study using a factorial design to test the effects of pregnancy diet and/or postpartum diet of breastfeeding moms on the establishment of the infant microbiome.

Funding Sources: MSU internal funds (AgBioResearch and faculty start-up).

RevDate: 2019-06-21

Otieno D, Pei Y, Gu I, et al (2019)

Effect of Quercetin on Non-shivering Thermogenesis and Intestinal Microbial Populations (P06-037-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.P06-037-19.

Objectives: Activation of non-shivering thermogenesis in adipose tissues and alteration in intestinal microbiome have been linked with improved obese condition. With emerging evidences of dietary compounds to prevent obesity, the objective of this study was to examine whether quercetin activates non-shivering thermogenesis in adipose tissues and influences intestinal microbiome, which eventually improves obese condition.

Methods: Four-week-old C57BL/6 male mice were fed either a low-fat diet (LFD) or a high-fat diet (HFD) with or without 1% quercetin (Q) for 16 weeks. On the completion of the feeding study, brown adipose tissue (BAT), white adipose tissue (WAT), and cecum were collected. Total RNA was extracted from BAT and WAT, and then cDNA was synthesized. The expression of genes that are involved in the regulation of non-shivering thermogenesis such as uncoupling protein 1 (ucp1), cell death-inducing DFFA-like effector A (cidea), peroxisome proliferator-activated receptor gamma (pparγ), pparγ-coactivator 1 alpha (pgc1α), fibroblast growth factor 21 (fgf21), positive regulatory domain containing 16 (prdm16), and T-box protein 1 (tbx1) were determined by a real-time PCR. The expression of the proteins such as UCP1 and AMP-activated protein kinase (AMPK) was assessed by western blot analysis. Microbial populations in cecum were analyzed via the Illumnia MiSeq sequencing platform and QIIME (Quantitative Insights Into Microbial Ecology) Software.

Results: Mice fed HFDQ showed reduced body weight and retroperitoneal (R) WAT weight compared to mice fed HFD. Quercetin supplementation increased the expression of ucp1, prdm16, pgc1α, cidea, and tbx1 genes in BAT and RWAT of mice fed HFD. The expression of UCP1 protein and phosphorylation of AMPK were increased. However, browning effect was not observed in other WATs. Mice fed LFDQ and HFDQ exhibited higher relative abundance of Bacteroidetes than mice fed LFD and HFD whereas the relative abundance of Firmicutes was decreased.

Conclusions: Quercetin may be a potential dietary compound that increases energy metabolism by activating BAT and attracting beige adipocytes in RWAT. In addition, quercetin-induced energy metabolism may have a correlation with changes of microbial populations in intestine.

Funding Sources: The work was supported by USDA.

RevDate: 2019-06-21

Lee SG, Lei C, Melough M, et al (2019)

Impacts of Aging and Blackcurrant Supplementation on the Gut Microbiome Profile of Female Mice (P20-031-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-031-19.

Objectives: Blackcurrant, an anthocyanin-rich berry, has multiple health benefits. The purpose of this study was to examine the impacts of blackcurrant supplementation and aging on gut bacterial communities in female mice.

Methods: Three-month and 18-month old female mice were provided standard chow diets with or without anthocyanin-rich blackcurrant extract (BC) (1% w/w) for four months. Upon study completion, fecal samples were collected directly from the animals' colons. Microbiome DNA was extracted from the fecal samples and the V3-V4 regions of their 16S rRNA gene were amplified and sequenced using.

Results: Taxonomic analysis showed a significantly decrease in alpha diversity in aged female mice, compared to young counterparts. BC consumption did not alter the alpha diversity in either young or aged mice compared to control diets. For beta diversity, we observed the clustering was associated with age but not diet. The phylogenic abundance analysis showed that the relative abundance of several phyla, including Firmicutes, Bacteroidetes, Cyanobacteria, Proteobacteria, and Tenericutes was higher in aged compared to young mice. Among them, the abundance of Firmicutes was downregulated by BC in the young but not the aged mice. The abundance of Bacteroidetes was increased by BC in both the young and the aged groups. Noticeably, Verrucomicrobia was the only phylum whose relative abundance was upregulated in the aged female mice compared to the young mice. Meanwhile, its relative abundance in the aged group was suppressed by BC. Interestingly, Desulfovibrio, which is the most representative sulfate-reducing genus, was detectable only in young female mice, and BC increased its relative abundance.

Conclusions: Our results characterized the gut microbiome compositions in young and aged female mice, and indicated that the gut microbiome of young and aged female mice responded differently to four month BC administration. Through additional research, the microbial alterations observed in this study should be further investigated to inform our understanding of the effect of BC on the gut microbiome, the possible health benefits related to these changes, and the differing effects of BC supplementation across populations.

Funding Sources: This study was supported by the USDA NIFA Seed Grant (#2016-67018-24492) and the University of Connecticut Foundation Esperance Funds to Dr. Ock K. Chun. We thank the National Institute on Aging for providing aged mice for the project and Just the Berries Ltd. for providing the blackcurrant extract.

RevDate: 2019-06-21

Huey S, Rajagopalan K, Venkatramanan S, et al (2019)

Diet and the Gut Microbiome in 10-18-Month-Old Children Living in Urban Slums of Mumbai, India (OR01-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR01-08-19.

Objectives: 1. To characterize the gut microbiome and 2. explore associations between dietary intake and gut microbiome composition and predicted function among children at screening for participation in a randomized controlled feeding trial in urban slums of Mumbai, India.

Methods: Young children (10-18 months old) living in urban slums of Mumbai were screened from March to November 2017 after obtaining informed consent from caregivers. Nutrient intakes from 24-hour dietary recall were analyzed as absolute intakes, % of RDA, and using the nutrient residual to adjust for energy intake. DNA extracted from rectal swabs was sequenced (16S rRNA V3-V4 region; Illumina MiSeq) and further processed using QIIME2 and PICRUSt algorithm. Linear regression was used to estimate associations between nutrient intakes (adjusted for age and sex) and measures of gut microbiome α-diversity, including Shannon Index, Chao1 estimator, observed OTUs, Proteobacteria relative abundance, Firmicutes: Bacteroidetes ratio, and predicted KEGG pathways. Statistical analysis was performed using RStudio, and SAS 9.4.

Results: A subset of 53 children with rectal swabs collected were included. Sequencing yielded 8984,126 reads including 2173 unique operational taxonomic units (OTUs). Mean relative abundance of Proteobacteria was 78.2%. Shannon Diversity Index was positively associated with absolute intakes of total carotenoids and beta-carotene. Children with adequate intakes of zinc and beta-carotene had a higher mean Shannon Diversity Index. The Chao1 estimator was positively associated with absolute intakes of calcium. The number of observed OTUs was positively associated with calcium and zinc intakes. The predicted gene counts for germination, sporulation, amoebiasis, and protein digestion and absorption pathways were also associated with both macro- and micro-nutrient intakes.

Conclusions: The gut microbiome in this sample of young children in Mumbai was dominated by Proteobacteria, which includes many potentially pathogenic species. Dietary intakes of macro- and micronutrients were associated with measures of diversity and predicted functional pathways after adjustment for age and sex, warranting further longitudinal study of the diet's impact on the microbiome particularly in young children.

Funding Sources: HarvestPlus.

RevDate: 2019-06-21

Frame L, Costa E, S Jackson (2019)

Current Explorations of Nutrition and the Gut Microbiome: A Systematic Review (P20-032-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-032-19.

Objectives: The ability to measure and describe the microbiome has led to a surge in information about the gut microbiome and its role in health and disease. The relationship between nutrition and the gut microbiome is central, as the diet is a source of microbiota, a source of fuel for the microbiota, and an indicator of the composition of the gut microbiome. We aim to assess the current understanding of the interactions between nutrition and the gut microbiome in healthy adults. A solid understanding of the interactions between nutrition and a healthy gut microbiome will form the foundation for understanding the role in disease prevention and treatment.

Methods: PubMed and Google Scholar searches for review articles relating to nutrition and the gut microbiome in healthy adults led to the inclusion of 38 articles in this systematic review.

Results: Much of the research has focused on carbohydrates in the form of dietary fiber, which are fuel for the gut microbiota. The beneficial effects of fiber have centered on Short Chain Fatty Acids (SCFAs) that are required by colonocytes (barrier function), improve absorption (minerals, water), and reduce intestinal transit time (colon cancer). Contrastingly, a low fiber, high protein diet promotes microbial protein metabolism, leading to potentially dangerous by-products that can stagnate in the gut.The bidirectional relationship between micronutrition and the gut microbiome is emerging. The microbiota utilize and produce micronutrients, leading to confounding relationships between nutritional status and biologic micronutrient concentrations, chiefly the B and K vitamins.While promising, the study of non-nutritive food components (polyphenols) and the gut microbiome is in its infancy. The role of other food components (food additives, contaminants) warrant exploration and are a significant research gap to-date.

Conclusions: Diet and nutrition have profound effects on the gut microbiome composition. This, in turn, affects a wide array of metabolic, hormonal, and neurological processes that influence our health and disease. Currently, there is no consensus in the scientific community on what defines a "healthy" gut microbiome. Future research must consider individual responses to diet and the role of diet in the response of the gut microbiome to interventions.

Funding Sources: N/A.

RevDate: 2019-06-21

Cross TW, Hutchison E, Coulthurst J, et al (2019)

A Partnership in the Making: Metabolic Phenotype Determined by the Combination of Dietary Fiber and the Gut Microbiome (FS07-03-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.FS07-03-19.

Objectives: Dietary fiber consumption improves cardiometabolic health, partly by enhancing microbial diversity and increasing production of butyrate in the distal gut. However, it is unclear whether the benefits associated with different types of fiber vary based on the gut microbiota composition. We surveyed nine different human gut microbial communities by characterizing them in germ-free mice and selected two communities based on their butyrate-producing capacity ("B") and diversity ("D") (i.e., high- vs. low-BD communities). Our objective was to assess the role of high- vs. low-BD communities on the metabolic effects elicited by the consumption of various dietary fibers.

Methods: We formulated seven diets with different sources of dietary fiber (10% wt/wt): i) resistant starch type 2 (RS2); ii) RS4; iii) inulin; iv) short-chain fructooligosaccharides (scFOS); v) pectin, vi) assorted fiber (a combination of the 5 fermentable fibers), and vii) cellulose (a non-fermentable control). Germ-free C57BL/6 male mice were colonized with either the high- or low-BD communities and fed the assorted fiber diet for 2 weeks to reach stability of microbial engraftment. Mice were then switched to one of the 7 diets for 4 weeks (n = 7-10/group; 117 mice total). We quantified cecal level of short-chain fatty acids and assessed the gut microbiota composition using 16S rRNA gene-based sequencing.

Results: Mice colonized with the high-BD community have lower body weight and fat mass compared to the low-BD community when fermentable-fiber sources RS2, inulin, or assorted fiber were present in the diet. Body weight did not differ between the two communities when mice were fed RS4, scFOS, pectin, or cellulose diets. Lower body weight and fat mass were associated with greater cecal butyrate concentrations and microbial diversity.

Conclusions: The efficacy of dietary fiber interventions on metabolic health varies based on the gut microbiota composition. Overall, our results suggest that dietary fiber supplementations need to be matched with the metabolic potential of the gut microbiome.

Funding Sources: Fondation Leducq, USDA, and NIH.

RevDate: 2019-06-21

Berry S, Valdes A, Davies R, et al (2019)

Large Inter-individual Variation in Postprandial Lipemia Following a Mixed Meal in over 1000 Twins and Singletons from the UK and US: The PREDICT I Study (OR19-06-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz046.OR19-06-19.

Objectives: Postprandial lipemia is an important risk factor for cardiovascular disease, independent of fasting levels, and is influenced by multiple factors including; environmental, genetic, metabolic, metagenomic and the meal-context. Postprandial lipemic responses may therefore differ between individuals, however previously this has only been studied in limited numbers. The PREDICT I study is the largest study to date to measure inter-individual variability in postprandial lipemic responses using a standardized test meal model.

Methods: A multi-center postprandial study of 1000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from US, assessed postprandial (hourly 0-6h) lipemic responses to sequential mixed-nutrient dietary challenges (50g fat and 85g carbohydrate at 0h; 22g fat and 71g carbohydrate at 4h) in a clinical setting. Inter-individual variability in postprandial triacylglycerol (TG) responses was measured for incremental area under the curve (iAUC), Cmax, Tmax and increase above fasting at 5h (mean peak concentration time-point).

Results: Analysis showed high inter-individual variability in postprandial lipemic responses (Figures 1-3) in the tightly controlled clinic setting (interim analysis of n = 537); IQR (median) was; iAUC (0-6h) 2.34 (2.38) mmol/L.h; Cmax 1.32 (2.02) mmol/L; Tmax 30.0 (300) min; and increase above fasting at 5h 0.92 (0.95). TG variation was higher in the non-fasting versus the fasting state; fasting TG concentration IQR (median); 0.57 (0.91) mmol/L.

Conclusions: The large variation in the magnitude and pattern of lipemic responses to identical meals in healthy people demonstrates the limitations of using the group mean and the importance of individualized dietary approaches. Ongoing exploration in PREDICT I of the determinants of postprandial lipemic responses considering environmental, genetic, metagenomic and microbiome variables will significantly advance our ability to predict an individual's postprandial response.

Funding Sources: NIHR, Wellcome Trust, Zoe Global Ltd.

RevDate: 2019-06-21

Porter N, Brewer L, Anderson K, et al (2019)

Sexually Dimorphic Effects of Dietary Vitamin D3 Supplementation on Cognition and the Gut Microbiome in Aging Rats (P14-006-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz052.P14-006-19.

Objectives: Increasing evidence suggests that vitamin D plays a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Here, we determined if a long-term enhanced vitamin D (VitD3, cholecalciferol) diet, higher than the standard dietary level, maintains or improves cognitive function in aging male and female rats. We also examined if the high VitD3 diet affected the gut microbiome.

Methods: Beginning at 12 months of age 20 male and 20 female F344 rats were fed an AIN-93 diet containing either standard (1000 IU/kg diet) or higher (10,000 IU/kg) VitD3 for 6 months. The Morris water maze (MWM) was then used to assess learning and memory. Following the MWM, the gut microbiome from undigested chyme collected from the intestinal cecum was identified and taxonomically classified by Argonne National Laboratory using 16S rRNA sequences. ZRT Laboratory determined 25-(OH)VitD3 levels from cardiac blood. A two-way ANOVA and Tukey post-hoc was used to test for statistical significance.

Results: After 3 days of training the probe test on day 4 indicated that the higher VitD3 diet significantly reduced path length and latency (P = 0.01) to the digital platform in females but not males. On day 5 platform location was changed and animals received one day of reversal training. On day 8, three days after reversal training, the reversal probe indicated that higher dietary VitD3 improved performance in males but not females by significantly reducing path length and latency to the digital platform (P < 0.05). Analyses of the cecal microbiome content indicated that for numerous bacteria sex specific differences were present. Further, the Shannon Diversity Index of the gut microbiome indicated a significant treatment effect of higher dietary VitD3 in females (P = 0.01). The higher VitD3 diet significantly elevated 25-(OH)VitD3 blood levels.

Conclusions: These results indicate that a high VitD3 diet may preserve cognitive acuity during aging. Further, VitD3 may have sexually dimorphic effects on memory formation. The present results replicate our previous study that a high VitD3 diet preserves cognition in aging male rats (Latimer et al. 2014). The microbiome showed sexually dimorphic differences and the high VitD3 diet appeared to affect the microbiome in females more than males. The significance of this is not clear.

Funding Sources: NIA, NIDDK.

RevDate: 2019-06-21

Abernathy B, Schoenfuss T, D Gallaher (2019)

Polylactose, a Novel Prebiotic Dietary Fiber, Reduces Adiposity and Hepatic Lipid Accumulation (P20-027-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-027-19.

Objectives: Polylactose is a novel dietary fiber, synthesized by extrusion of lactose. To evaluate its potential as a prebiotic, we determined its fermentability, effect on the microbiome, and its effects on adiposity, fatty liver, and liver cholesterol in a diet-induced obesity animal model.

Methods: 72 male Wistar rats were fed normal fat (NF) or high fat (HF, 51% fat by kcal) diets containing various fibers (6% fiber of interest and 3% cellulose, by weight); including cellulose (NFC and HFC), polylactose (HFPL), matched lactose (HFML), matched to the residual lactose in the HFPL diet, and two established prebiotic fibers, polydextrose (HFPD) and fructooligosaccharides (HFFOS). After 10 weeks on experimental diets, organs were harvested and cecal contents collected for analysis.

Results: There were no significant differences in final body weights among the groups, nor did average daily food intake differ significantly among the HF-fed groups. HFPL animals had greater cecal weight (empty) and lower cecal contents pH when compared to all other groups, suggesting that polylactose is much more vigorously fermented than the other prebiotic fibers. This was also indicated by an increase in taxonomical abundance of probiotic species in the cecum. Epididymal fat pad weight was significantly decreased in the HFPL animals compared to all other HF groups (P < 0.05) and did not differ from the normal fat control (NFC). Liver lipids and cholesterol were significantly reduced in HFPL fed animals when compared to HFC fed animals and were numerically lower than all other HF groups. Transcriptome analysis of the liver revealed increased lipid oxidation and decrease lipid synthesis pathway expression, providing insights into mechanisms of reduction of lipid accumulation in the liver.

Conclusions: Polylactose is a vigorously fermentable fiber and elicits a beneficial change in the gut microbiome. We also demonstrate that consuming polylactose, in the context of a high fat diet, prevents the accumulation of body fat normally seen with this diet, as well as reduced lipid and cholesterol accumulation in the liver. As these effects of polylactose were greater than those of two established prebiotics, fructooligosaccharides and polydextrose, this suggests that polylactose is a potent prebiotic.

Funding Sources: Midwest Dairy Association.

RevDate: 2019-06-21

Mehal W, Dioletis E, Paiva R, et al (2019)

The Fermented Soy Beverage Q-CAN® Plus Induces Changes in the Oral and Intestinal Microbiome (P20-018-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-018-19.

Objectives: To better understand the mechanisms for the beneficial effects of Q-CAN we identified changes in the fecal and oral microbiome in healthy subjects. Due to the high prevalence of obesity, and the known differences in the microbiome in obesity we want to test the effects on Q-CAN on lean and obese subjects.

Methods: Prospective study of lean (10) and obese (10) subjects. 11 clinic visits over 14 weeks. 237 ml of soy was dispensed at visit 3 and was consumed twice daily for 4 weeks until visit 7. Visits 8-11 were post treatment. Microbial DNA was extracted from saliva and stool samples, amplified against the V4 region of the 16S ribosomal RNA gene. Raw DNA sequencing data analyzed with the QIIME 1.9.1 bioinformatics pipeline. samples producing > 5000 reads were considered for analysis, and the cutoff abundance was 0.01%. Statistical validation was performed using the SAS software package to calculate Least Squares Means (LSM) and group difference of LSM. 440 samples were collected in total, 424 of which were productive and yielded good quality data.

Results: STOOL. Obese had higher firmicute/bacteroidetes ratio compared to the lean group. At phylum level the gut microbiome of the obese group shows a trend for decreased firmicute/bacteroidetes ratio while taking Q-CAN. In the lean population actinobacteria show a statistically significant increase (0.0095 ± 0.0039, P = 0.02) during soy consumption compared to baseline. Several genera show a significant decrease in abundance in the obese group upon soy withdrawal including Faecalibacterium, Bifidobacterium and Sutterella. Dorea is increasing in obese group and Lachnospiraceae genus is decreasing in the lean group when comparing samples during consumption to baseline. ORAL. Veillonella and Oribacterium increased during soy consumption vs baseline, while Neisseria is decreasing.

Conclusions: Fermented soy consumption introduced changes in the abundance of the oral and gut microbiome. The decreasing firmicute to Bacteroidetes ratio is particularly promising as a low ratio is associated with lean body type, while a high ratio is associated with obese body type. The shift in the microbiome in obese individuals may be associated with health benefits such as reduced inflammation, or improvement in the metabolic phenotype.

Funding Sources: Beso Biological Research, Inc.

RevDate: 2019-06-21

Anderson K, Keirns B, Ojo B, et al (2019)

Contribution of Carbohydrates and Polyphenols to Dried Plum's Prebiotic Activity (P20-029-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-029-19.

Objectives: In addition to bone protective effects, dried plums (DP) also prevent weight gain in animal models of ovarian hormone deficiency. The aim of this project was to investigate the contribution of the polyphenol (PP) and carbohydrate (CHO) components of DP on weight gain and body composition, as well as their effects on the gut environment.

Methods: Two studies were performed using 8-wk-old C57BL/6 female mice that were sham-operated (Sham) or ovariectomized (Ovx), and allowed to lose bone prior to treatment for 5 or 10 wks. In Study 1, Sham and Ovx mice were assigned to control (AIN-93 M), control diet with added DP (25% w/w) or a crude PP extract (CPE; equivalent PP to DP). In Study 2, Ovx mice were randomized to diets with the CPE fractions, PP or CHO, in a 2x2 factorial design. At the end of each study, bone mineral density (BMD) and body composition were assessed. Cecal bacterial taxa and short chain fatty acids (SCFA) were characterized at 5 and 10 wks, respectively. Non-microbiome data were analyzed using 1-way or 2-way ANOVA (SAS, Version 9.4).

Results: In Study 1, Ovx increased (P < 0.01) weight gain, %fat and abdominal white adipose tissue (WAT), and DP and CPE mitigated (P < 0.05) this response at 5 and 10 wks. Likewise, DP and CPE reversed the Ovx-induced decrease in BMD at both time points. DP and CPE enriched the SCFA-producing family, Lachnospiraceae, as well as Coriobacteriaceae and Verrucomicrobiaceae, which are associated with weight regulation. Cecal acetic, propionic, n-butyric and n-valeric acids were increased by DP and CPE compared to Ovx-control, but the response was greater with DP. In Study 2, CHO with or without PP, reduced Ovx-induced weight gain (P < 0.01), %fat (P < 0.001), WAT (P < 0.01) and reversed the loss of BMD at both time points. Compared to CPE, Verrucomicrobiaceae was more abundant with the PP group, but there was no change in β diversity with the CHO group. All of the assessed SCFA were increased with CHO, regardless of PP content, while n-butyric acid and the two isomers of valeric acid were independently enhanced by PP. Among the assessed outcomes, there were no additive effects of CHO and PP.

Conclusions: Although their prebiotic effects differ, both the CHO and PP components contribute to DP's effects on weight gain and body composition.

Funding Sources: OCAST; California Dried Plum Board.

RevDate: 2019-06-21

Saxby S, Li Y, Lee C, et al (2019)

Assessing the Prebiotic Potential of Taro (Colocasia esculenta) with Probiotic Lactobacillus Species in an in Vitro Human Digestion System (P20-022-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-022-19.

Objectives: Taro (Colocasia escuknta), a culturally important staple food of the native Hawaiian diet, is high in fiber content, reaching 4.1 g/100 g. Prebiotics are carbohydrates that are indigestible by the digestive tract, which can selectively stimulate probiotic growth and/or activities in the colon. Due to taro's high fiber content, it was hypothesized to have prebiotic potential. This study aimed to evaluate the effect of taro on the growth and adherence of probiotic Lactobacillus species in an in vitro human digestion system for the improvement of the human gut microbiome.

Methods: Four probiotic Lactobacillus species, including L. acidophilus, L. paracasei, L. rhamnosus, and L. plantarum, were individually paired with 2% (w/v) taro. In addition to taro, 2% (w/v) glucose and inulin were used as controls. The pairings were subjected to an in vitro human digestive tract simulation of the mouth, stomach, and intestinal conditions to assess the fate of tested probiotics. Furthermore, an auto-agglutination assay was conducted to evaluate the effect of taro on self-agglutination of the individual probiotics. Lastly, the Caco-2 cell line was used to determine whether taro could influence the ability of tested probiotics to adhere to human intestinal epithelial cells.

Results: Results indicated that L. acidophilus, L. paracasei, and L. plantarum experienced greater growth in the simulated intestinal tract when paired with taro than with inulin or glucose. In addition, L. paracasei showed strong self-agglutination ability and had the greatest adherence percentage to Caco-2 cells.

Conclusions: In conclusion, taro is a strain-specific potential prebiotic that can be utilized as a dietary aid to modulate a healthy gut microbiota.

Funding Sources: USDA-ARS.USDA-NIFA HatchUniversity of Hawai'i Mānoa MahiMicrobes Program.

RevDate: 2019-06-21

Wernimont S, Fritsch D, Jackson M, et al (2019)

Specialized Dietary Fibers Alter Microbiome Composition & Promote Fermentative Metabolism in the Lower Gastrointestinal Tract of Healthy Adult Cats (P20-045-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-045-19.

Objectives: The feline gastrointestinal (GI) microbiome is capable of fermenting fibers. We evaluated specialized dietary plant fibers on feline GI microbiome composition & metabolism.

Methods: 46 healthy adult cats were fed control food (CF) for 4 wks & test food (TF) for 8 wks (CF: 4129 kcal/kg, 1.6 g total dietary fiber, TDF; 0.7 g soluble fiber, SF; & 0.9 g insoluble fiber, INSF, per 100 kcal; TF: 4010 kcal/kg, 3.2 g TDF, 0.3 g SF, 2.9 g INSF per 100 kcal). All foods were complete balanced dry products & met 2017 AAFCO maintenance guidelines. CF fiber sources: cracked pearled barley, corn, dried beet pulp, fructooligosaccharides (FOS) & psyllium seed husk; TF: corn, ground pecan shells, cracked pearled barley, whole grain oats, dried beet pulp, pea fiber, flaxseed, dried citrus pulp, pumpkin, cranberry pomace, FOS & psyllium seed husk. Feces were collected after 4 wks of CF & after 4 & 8 wks of TF, cleaned of litter, homogenized, & frozen at -70C within 1 hour of defecation. Cats had free access to water, natural daylight & enrichment from toys, other cats & people. The study was reviewed & approved by the Institutional Animal Care & Use Committee, Hill's Pet Nutrition, Inc. Fecal microbiome 16 s rRNA sequencing was performed using Illumina MiSeq & processed by Mothur. Predicted microbial functions were determined by PICRUSt & analyzed using PERMANOVA. The copy number corrected OTU counts were analyzed using negative binomial mixed models. Fecal short chain fatty acids (SCFA) were analyzed using liquid-liquid extraction & gas chromatography with flame ionization detection. Results significant at P < 0.05 are reported.

Results: At 4 & 8 wks, TF significantly increased acetic & propionic acids, decreased isobutyric, 2-methylbutyric, & isovaleric acids. The genera Peptococcus, Succinivibrio & Enterococcus were significantly decreased vs. CF at 4 & 8 wks while Blautia, Bacteroides, & Turicibacter were significantly increased vs. CF at 4 & 8 wks. Predicted microbial functions representing arginine, benzoate, butyrate, phenylalanine, propionate, tryptophan & tyrosine metabolic pathways were significantly different from CF at 4 wks.

Conclusions: TF shifts feline GI microbiome composition & metabolism toward saccharolytic fermentation & decreases putrefactive metabolites, characteristics which may benefit feline GI health.

Funding Sources: This study was funded by Hill's Pet Nutrition, Inc.

RevDate: 2019-06-21

Benninghoff A, Phatak S, K Hintze (2019)

Consumption of Black Raspberries Altered the Composition of the Fecal Microbiome in Mice Fed a Western Type Diet (OR04-01-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz030.OR04-01-19.

Objectives: Dietary strategies to reduce colonic inflammation and promote gut homeostasis may markedly reduce the risk of colitis-associated colorectal cancer. Previously, we showed that dietary supplementation with black raspberries significantly suppressed colitis and colon tumorigenesis promoted by the consumption a Western type diet in mice. In this study, our goal was to assess the impact of consumption of the TWD with and without black raspberry supplementation on the composition of the fecal microbiome over the course of disease development.

Methods: C57BL/6 J male mice were fed a standard diet (AIN93G), the total Western diet (TWD), TWD + 5% (w/w) black raspberry powder (BRB) or TWD + 10% (w/w) BRB for 16 weeks total. After two weeks of feeding test diets, all mice were dosed with axozymethane and provided 1% dextran sodium sulfate in drinking water for 10 days to promote colonic inflammation and tumorigenesis. Composition of the fecal microbiome was determined by standard 16S rRNA sequencing following two weeks of dietary treatment, during active colitis immediately following DSS treatment and again two weeks later during the recovery period.

Results: Fecal microbiome profiles in mice fed diets supplemented with 5 or 10% BRB were distinct from those fed AIN93G or TWD diets, shown by significant differences in beta diversity at each of the time points (unweighted unifrac distance, permanova P < 0.01). During active colitis, alpha diversity was significantly reduced in mice fed TWD + 10%BRB compared to TWD-fed positive controls (Chao1, P = 0.04; Shannon, P = 0.006). Also of interest, LEfSe analysis identified bacteria families Bifidobacteriacea (Bifidobacteriumpseudolongum), Streptococcaceae (genus Lactococcus), and Turicibacteraceae (genus Turicibacter) as discriminating taxa for mice fed TWD with BRB supplementation compared to those fed TWD. Also during colitis, both Bifidobacteriaceae and Turicibacteraceae families also distinguished TWD + BRB groups from mice fed AIN93G diet, whereas Verrucomicrobiaceae (Akkermansia muciniphila) distinguished TWD-fed mice from AIN93G negative controls.

Conclusions: Consumption of BRB at diet-relevant concentrations altered the composition of the gut microbiome in favor of some known health-promoting bacteria, a change the may explain the suppression of colitis and colon tumorigenesis previously observed.

Funding Sources: USDA NIFA Grant# 2018-67017-27516 and Utah Agricultural Experiment Station Project UTA-1178.

RevDate: 2019-06-21

Kok CR, Brabec B, Chichlowski M, et al (2019)

Stool pH and Short/Branched Chain Fatty Acids in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (P11-076-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.P11-076-19.

Objectives: Infant feeding influences early development of the gut microbiome, colonization pattern, and community structure. Metabolites, including short- and branched-chain fatty acids (S/BCFA) (e.g., butyrate, propionate), produced by colonic bacteria serve as signaling molecules, influence immunity, and reduce luminal pH in the gastrointestinal environment. The objective of this study was to evaluate stool S/BCFA and pH in infants fed with different sources of dietary protein.

Methods: In this multicenter, double-blind, controlled, parallel-group, pilot study, healthy term infants were randomized to receive one of two infant formulas (IF): amino-acid based (AAF; n = 25) or extensively hydrolyzed cow's milk protein (EHF; n = 28) from Baseline (1-7 days of age) up to 60 days of age. A human milk reference group (HM; n = 25) received mother's own milk over the same period. Diethyl ether extractions of S/BCFA from stool samples (Baseline, Day 30, and Day 60) were quantified by gas chromatography (Clarus 580; PerkinElmer) using a fused silica capillary column (Nukol 30m × 0.25mm id × 0.25μm film). Mean stool S/BCFA (μmol/g) and pH were analyzed by repeated measures analysis of variance (ANOVA).

Results: Complete stool data (all study time points) were available for 49 participants. Stool pH (∼6) was similar among groups at Baseline with no significant changes for HM and EHF groups through Day 60. The AAF group was significantly higher at Days 30 and 60 (Figure 1). Total SCFA were similar for all groups through Day 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group (P = 0.026) and was significantly higher vs HM at Days 30 and 60 (P = 0.0009 and 0.0004 respectively). Butyrate was significantly higher for AAF vs HM at Day 60 only (P = 0.038). Propionate was significantly higher for EHF and AAF at Day 30 (P = 0.0009 and < 0.0001 respectively) and AAF only at Day 60 (P = 0.005) vs HM. Total and individual BCFA increased for AAF and EHF groups vs HM through Day 60.

Conclusions: Distinct patterns of pH and microbial metabolites were demonstrated for infants receiving mother's own milk compared to amino acid-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites.

Funding Sources: Mead Johnson Pediatric Nutrition Institute.

RevDate: 2019-06-21

Wu D, Zhou F, Upadhyaya B, et al (2019)

Microbial mRNAs in Bovine Milk Exosomes Are Bioavailable in Humans and Mice and Increase Survival of Mice Challenged with Influenza A (OR12-07-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz049.OR12-07-19.

Objectives: Exosomes are natural nanoparticles that facilitate cell-to-cell communication by transferring RNAs from donor to recipient cells. Previous studies focused on microRNA cargos and disregarded mRNAs. Exosomes and RNA cargos may be absorbed from milk. RNAs elicit antiviral responses by activating interferon type I (IFN) and NF-kappa B (NF-kB) signaling (Figure 1A).To assess whether 1) bovine milk exosomes (BME) contain microbial mRNAs, 2) microbial mRNAs are bioavailable in humans and mice, and 3) microbial mRNAs activate antiviral responses in reporter cells and mice.

Methods: The mRNA content in BME was assessed by RNA-sequencing. mRNA bioavailability was assessed by RNA-sequencing analysis of human plasma before and 4 h after consumption of 1 L milk and by administering BME transfected with synthetic, fluorophore (IRDye)-labeled Pseudomonas fluorescens capB mRNA to Balb/c mice by oral gavage. (capB mRNA was abundantly expressed in all BME samples sequenced.) Antiviral responses were assessed using liposomes loaded with capB mRNA and cultured with IFN and NF-kB J774 reporter macrophages, and by survival curves of mice fed BME-free or BME-sufficient diets and challenged with influenza A virus. Unpaired t-test was used for statistical analyses; P < 0.05 was considered significant.

Results: About 50% of the mRNA-sequencing reads in BME were non-bovine; after contig assembly, up to two thirds of the non-bovine reads mapped to microbial mRNAs (Figure 1B). IRDye-capB mRNA accumulated in murine intestinal mucosa and liver (and perhaps brain) 6 h and 24 h, respectively, after oral gavage (Figure 2). Microbial mRNAs, including 55 and 36 mRNAs from P. fluorescens and E. coli were detected in human plasma after but not before a milk meal (Tables 1, 2). capB mRNA-loaded liposomes activated NF-kB and IFN signaling in reporter macrophages (Figure 3A). C57BL/6 mice fed a BME-depleted diet died within 11 days of influenza A challenge whereas controls fed a BME-sufficient diet survived (Figure 3B).

Conclusions: This is the first report to suggest a novel interaction between microbiome and hosts: microbial mRNAs in BME are bioavailable, activate antiviral IFN and NF-kB pathways and increase resistance to influenza A.

Funding Sources: NIFA, NIH, Gates Foundation, PureTech Health, USDA Hatch & Multistate. J.Z. is a consultant for PureTech.

RevDate: 2019-06-21

Chen CP, Wu WK, Panyod S, et al (2019)

Cardiovascular Disease Protective Effect of Allicin Through Gut Microbiota Modulation (FS07-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.FS07-08-19.

Objectives: Red meat consumption can promote atherosclerosis since the gut microbiota can metabolize L-carnitine from meat into trimethylamine N-oxide (TMAO) which is a causative risk for cardiovascular disease. Garlic has long been associated with health benefits. Allicin is a major bioactive compound typically found in blend fresh garlic. It possesses the antibacterial, anti-oxidant, and cholesterol-lowering effects. The aim of this study is to investigate the effect allicin on the gut microbiota and its metabolites on cardiovascular disease by using the long-term carnitine treatment ApoE (-/-) mice model.

Methods: 8-week old male ApoE (-/-) mice were divided into 4 groups: (1) Control, (2) 1.3% Carnitine, (3) Allicin (10 mg/kg), and (4) 1.3% Carnitine + Allicin (10 mg/kg). After 15 weeks, we performed the carnitine challenge test by oral gavage of d9-carnitine to evaluate the TMAO production ability of the gut microbiota. The serum was analyzed for carnitine, trimethylamine (TMA) and TMAO levels by using LC-MS/MS. Other biochemistry was checked by an automatic blood analyzer. Morphological changes of aortic plaque formation were observed using oil red staining. The gut microbiome was analyzed by using 16S rDNA amplicon sequencing in Illumina Miseq platform.

Results: The results showed that allicin supplementation in the carnitine group exhibited the reduction of aortic lesion up to 34.2% as compared with carnitine group without allicin supplementation (P < 0.01). The carnitine challenge test indicated the d9-TMAO level of carnitine with allicin supplementation group tend to be reduced compared with carnitine-fed mice. Principal coordinate analysis of the feces microbiota composition was significantly different (ADONIS: P < 0.001) for each group. The linear discriminant analysis (LDA) effect size (LEfSe) results demonstrated that Akkermansia was enriched in the carnitine-fed group. In contrast, the carnitine-fed mice with allicin supplementation were abundance with Lachnospiraceae.

Conclusions: Allicin may exhibit the cardiovascular disease protective effect through modulation of gut microbiota-TMAO-atherosclerosis pathway.

Funding Sources: MOST 107-2321-B-002 -017 -.

RevDate: 2019-06-21

Kay C, Everhart J, A Rathore (2019)

Managing Risks Associated with Establishing the Metabolome of Dietary Phytochemicals (P06-010-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.P06-010-19.

Objectives: Establishing the metabolome of dietary phytochemicals is complicated by the influence of the microbiome. Due to large numbers of human, microbial and hybrid human-microbial metabolites, false-positive identification via mass spectrometry (MS) is probable. Users must be aware of the influence of matrix and instrumental background environment upon the mass spectrum, which produce spectral features arising from fragmentation, gas-phase artifacts, molecular rearrangement, quasi-molecular ion or radical formation. Hydroxylated cyclic and polycyclic structures such as polyphenols are prone to multiple gas-phase artifacts, including water elimination (loss -17), hydrogen elimination (-1), radical fragmentation (loss -15, -14), Retro-Diels-Alder reactions (C-ring electron rearrangement; + or -2), or combinations thereof. In-source fragmentation is often observed for phase II conjugates, such as sulfate, glucuronide and glycine. Finally, polyphenol metabolites such as valerolactones, benzoic, phenylpropanoic and phenylacetic acids, are also products of MS fragmentation. As there are few reference standards available for confirmation or optimization, false-positive identification is likely. The objective of the present study was to highlight limitations with MS to ensure researchers make appropriate assumptions from their spectral data.

Methods: A quantitative metabolomics database comprising optimized spectral signals for fragmentation profiling of over 400 poly/phenols and metabolites was established using a UHPLC-coupled electrospray triple quadrupole-linear ion trap mass spectrometer (SCIEX QTRAP 6500+). Methods were established and utilized to interrogate over 3000 biospecimens derived from studies feeding various polyphenol-rich diets.

Results: Scanning for numerous metabolites reported in the literature using single transition monitoring, in both neat and extracted human and animal tissue matrices consistently identify peaks which were either artifacts, isomers, fragments or background noise, as confirmed relative to authentic reference standards.

Conclusions: Without ample MS experience, method development, validation and data interrogation, falsely identified metabolites will continue to occur and undoubtedly hinder future discovery.

Funding Sources: NIFA-USDA Hatch 1011757.

RevDate: 2019-06-21

Drall K, Tun H, Azad MB, et al (2019)

Clostridioides Difficile Colonization Is Differentially Associated with Gut Microbiota Composition in Breastfed versus Formula Fed Infants (OR01-02-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR01-02-19.

Objectives: Colonization with Clostridioides difficile occurs in up to half of infants and is predicted by formula feeding. Although this microbe does not appear to pose any immediate risks for infants, its presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting changes in the gut microbiome that may increase opportunity for colonization of pathogenic bacteria. We explored these compositional changes in exclusively breastfed, partially breastfed and exclusively formula fed infants to describe the microbial community and C. difficile colonization in infants with distinct diets.

Methods: This study includes 1562 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Infants provided a fecal sample at 3-4 months of age (Mean: 3.56, SD: 1.00) which was analyzed using 16S rRNA sequencing and targeted qPCR for C. difficile. Mode of feeding was recorded in a questionnaire at a 3 month follow-up visit. C. difficile colonization was defined as positive detection (CD+) in the fecal sample (reference: not present, CD-). Multivariate association with linear models (MaAslin) was used to determine changes in microbiota composition following arsine-square root transformation of relative abundances and FDR correction.

Results: The prevalence of C. difficile colonization among all infants was 30.9%. Colonization rates differed among feeding groups: 22.63% of exclusively breastfed infants, 35.96% of partially breastfed infants and 49.63% of exclusively formula fed infants (P < 0.001). Microbes of the genus Bifidobacterium were decreased in CD + exclusively breastfed infants compared to non-carriers of the same diet (q = 0.02). Additionally, Blautia, Coprococcus and Clostridium, of the Lachnospiraceae family, and microbes of the Bacteroidetes phylum were of higher relative abundance (all q < 0.01) in breastfed CD + infants (both partial and exclusive). In exclusively formula fed infants, C. difficile colonization was not significantly associated with microbiota composition.

Conclusions: C. difficile colonization may have a dysbiotic effect on the gut microbiota composition of breastfed infants, changes which have previously been associated with childhood atopy and obesity.

Funding Sources: Canadian Institutes of Health Research (CIHR).AllerGen Network of Centres of Excellence (NCE).

RevDate: 2019-06-21

Wong SY, Wu L, Lu P, et al (2019)

Drinking Watermelon Juice Shift the Gut Microbiome in Diabetic Mice (P20-025-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-025-19.

Objectives: Watermelon is a delicious and healthy fruit that contains low calories and is rich in carotenoids, vitamin A, vitamin C, citrulline, and other bioactive compounds. The health benefits of watermelon in diabetes are poorly understood. In the current study, we sought to determine the effects of watermelon juice on gut microbiome profile and blood glucose management in type 1 and type 2 diabetic mice.

Methods: Six-week-old male C57BL/6 J wild type (WT), db/db type 2 diabetic (db/db), and streptozocin (STZ)-induced type 1 (STZ) diabetic mice were fed a chow diet and given 50% or 100% watermelon juice or tape water during night cycle for 8 weeks. At the termination of the study, mice were fasted for 3 hrs prior to euthanization. Blood, cecal contents, and other tissues were collected for laboratory assessments. Plasma metabolic parameters and pro-inflammatory cytokines were monitored by a clinical analyzer and ELISA, respectively. Cecal microbiome was profiled by 16S rRNA sequencing and followed by bioinformatic analysis.

Results: Consumption of watermelon juice significantly lowered fasting blood glucose levels in both diabetic mouse models. The fasting insulin level was significantly decreased in db/db consuming watermelon juice, though it was undetectable in STZ mice, with or without watermelon juice. Drinking watermelon juice tremendously changed the gut microbiome composition. At the phylum level, the Firmicutes/Bacteroidetes ratio was significantly associated with genotype (e.g., WT vs STZ vs db/db) and diet (e.g., watermelon juice vs tap water). At the genus level, abundances of Ruminiclostridium_9, Parasutterella, and Clostridium_sensu_stricto_1 were increased in STZ mice with watermelon, and abundances of Oscillibacter and Ruminiclostridium were decreased in db/db mice with watermelon. Watermelon juice induced gut microbiome compositional changes also occurred at the species level.

Conclusions: Watermelon juice intervention causes a decrease in blood glucose level and shifts of the gut microbiome in both type 1 and type 2 mice.

Funding Sources: National watermelon board grant.

RevDate: 2019-06-21

Whisner C, Wyst KV, Petrov M, et al (2019)

Rapid Weight Gain and Feeding Practices in the First 6 Months of Life Are Associated with Dysbiosis of the Gut Microbiome in Toddlerhood (P21-032-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz041.P21-032-19.

Objectives: Nearly 10% of infants and toddlers carry excess weight for their length. Rapid weight gain (RWG; >+0.67 change in weight-for-age Z-score) and feeding practices from 0-6 months (mo) of life are strong determinants of obesity. Both RWG and feeding practices may influence the gut microbiome (GM), which in turn can affect obesity risk by increasing susceptibility to weight gain during infancy. Our goal was to evaluate differences in GM community structure at 36 months of age in relation to feeding practices and RWG in infancy.

Methods: Pregnant, obese Latinas (n = 36) recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children program took part in a larger randomized health education trial designed to prevent infant overweight. The intervention was delivered from 0-12 mo and participants were followed until 36 mo of age. At one, 6, and 12 mo, mothers reported infant feeding practices. RWG was categorized as >0.67 positive change in weight-for-age Z-score over the first 6 months of life. Microbial DNA from feces collected at 36 mo were sequenced using primers for the 16S rRNA gene V4 region. GM diversity metrics were examined using Kruskal-Wallis and PERMANOVA comparisons, adjusted for multiple comparisons, via Qiime2.

Results: Of the cohort, 12 children experienced RWG in the first 6 mo of life. Within-sample species number (richness, Shannon Diversity Index: P = 0.014) and evenness (Pielou's Index: P = 0.019) were significantly lower at 3 years among children experiencing RWG in infancy. Upon comparing GM community structure (beta-diversity), exclusively breastfed infants (N = 9) formed a separate cluster from combination or formula-fed infants driven by phylogenetic diversity and species presence/absence (unweighted UniFrac: P = 0.033; Jaccard: P = 0.014). Children introduced to solid foods before (N = 30) vs. after (N = 6) 6 mo (Bray Curtis: P = 0.056; weighted UniFrac: P = 0.071).

Conclusions: RWG and feeding practices in the first 6 mo of life appear to shape the GM in ways that last into toddlerhood. Identifying specific microbes may provide insights for intervention to prevent RWG. How shifts in the GM influence risk for childhood and adult obesity remain an area for exploration.

Funding Sources: R01DK096488 and ASU Obesity Solutions, Virginia G. Piper Foundation.

RevDate: 2019-06-21

Solano-Aguilar G, Shao J, Urban J, et al (2019)

Dietary Patterns Differentially Affect Microbiome Composition and Function in a Porcine Model of Obesity-related Metabolic Disorder (OR23-04-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR23-04-19.

Objectives: To determine the impact of two isocaloric diets containing (38% ,15% and 47% energy from fat, protein and carbohydrate, respectively): Western diet (WD) rich in saturated fat, refined carbohydrate, low in fiber and high in cholesterol, and a heart healthy diet (HHD) rich in unsaturated fat, unrefined carbohydrate, fruits/vegetables, high in fiber and low in cholesterol, on the composition and function of the gut microbiome.

Methods: Thirty-Ossabaw pigs were fed WD or HHD diets with half within each group therapeutically treated with statin (atorvastatin [Lipitor]). The fecal microbiome was analyzed one and six months after dietary intervention by 16S rRNA sequencing and metagenomic function was empirically inferred.

Results: Genus diversity was transiently affected with a reduced Shannon Diversity index one month after feeding the WD or HHD (FDR P < 0.05) with no change between groups at 6 months. Bacterial communities were clustered and separated by diet independent of gender and separated by treatment with statin in the HHD only. Verrucomicrobiaceae (Akkermansia) and Methanobacteriales (Methanobrevibacter) were increased in pigs as early as one month after feeding the HHD, as was Clostridiales and Bifidobacterium (associated with optimal intestinal health). There was an enrichment of Proteobacteria (Succinivibrionaceae, Desulfovibrionaceae) in pigs fed the WD. Additional members of the Firmicutes phylum were detected. Diet-dependent associations (all P < 0.05) were identified between Lachnospiraceae members and early host dyslipidemia, inflammation, and atheromatous lesions in the left anterior descending proximal (LAD) and LAD/Left circumflex (LCX) bifurcation six months post-intervention.

Conclusions: These data document for the first time a distinctive bacterial profile in Ossabaw pigs with a diet-induced dyslipidemia and early stage atherosclerosis. Taken together these results represent a new model to examine mechanistic pathways of dietary patterns and/or drug interactions and its effect on modulating microbiome in developing atherosclerosis.

Funding Sources: USDA project 8040-51530-056-00 and Inter Agency USDA Agreement 588-1950-9-001 between BHNRC and Jean Mayer USDA-HNRCA.

RevDate: 2019-06-21

Mendez R, Miranda C, Armour C, et al (2019)

Antiobesogenic Potential of Seaweed Dulse (Palmaria palmata) in High-fat Fed C57BL/6 J Mice (P21-014-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz041.P21-014-19.

Objectives: The growing obesity challenge around the world continues to warrant interventions that could mitigate disease onset and progression. This study aimed to evaluate the potential of seaweed supplementation using dulse (Palmaria palmata) and wakame (Undaria pinnatifida), in improving caloric management and insulin resistance, and mitigating inflammation and gut microbiome shifts in diet-induced obesity in C57BL/6 J mice.

Methods: Twenty-four individually-caged C57BL/6 J mice were fed ad libitum with a high-fat diet (HFD) with and without seaweed inclusion, and another 8 mice for low-fat control (n = 8). Freeze-dried dulse and wakame were incorporated in the test diets at 5% inclusion level. Glucose tolerance test was performed during week 4 to assess insulin resistance state of test animals. After 9 weeks, fresh fecal samples were collected from all 32 mice prior to necropsy. These were used for the gut microbiome analysis using MiSeq. Fecal triglyceride levels were determined using Infinity Triglycerides Kit while plasma Monocyte Chemoattractant Protein-1 (MCP-1) was quantified using ELISA.

Results: Despite higher feed intake, dulse-fed mice had lower feed efficiency, indicating less weight gain from same amount of diet. This group also showed improved early-phase insulin response compared to HFD and wakame-fed groups. Plasma inflammatory marker MCP-1 levels were also significantly reduced in dulse-fed mice. While liver triglyceride levels were not affected with the dietary inclusion, fecal samples showed that there was higher lipid being excreted in dulse-fed group. This suggests that caloric excess and inflammatory progression may have been mitigated by increased lipid excretion in the feces. Gut microbiome analysis showed that dulse-fed mice retained microflora composition that is comparable to those fed with low-fat diet.

Conclusions: Our work reveals that dulse supplementation improved obesity and associated metabolic parameters by increasing lipid excretion, improving early-phase insulin response, and mitigating both inflammation and gut microbiome shifts associated with HFD, more effectively than wakame. These provide initial evidences that dietary inclusion of dulse holds therapeutic promise in mitigating diet-induced obesity.

Funding Sources: Oregon State University Agricultural Research Foundation.

RevDate: 2019-06-21

Shafizadeh T, Frese S, G Casaburi (2019)

Maximizing Nutrient Availability for the Breastfed Infant Through Colonization with B. Infantis EVC001 (FS04-04-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.FS04-04-19.

Objectives: Human breastmilk contains complete nutrient composition required for the developing infant, including human milk oligosaccharides (HMO). These complex carbohydrates are indigestible by the infant alone, and require digestion by gut microbes, namely Bifidobacterium longum subsp. infantis (B. infantis). However, decades of C-section delivery, formula feeding and increasing exposure to antibiotics have contributed the loss of this critical infant-associated gut bacterium in developed countries. Therefore, restoring B. infantis to the infant gut was hypothesized to improve the nutritional utilization of human breastmilk in healthy term infants.

Methods: In an open trial, healthy, exclusively breastfed term infants were fed 1.8 × 1010 CFU B. infantis EVC001 daily from day 7-27 postnatal (n = 34; EVC001-fed), or breastmilk alone (n = 32; control group). Fecal samples, milk samples, and weekly self-reported data were collected and analyzed for infant gut microbiome composition and function, human milk oligosaccharide composition, and fecal metabolites. 16S rRNA sequencing and shotgun metagenome sequencing provided characterization of microbial communities from birth through 60 days postnatal.

Results: Infants fed B. infantis EVC001 were uniformly colonized with this organism at 1011 CFU/g feces, while infants in the control group had a median total Bifidobacterium level below 10^5 CFU/g feces, despite exclusive breastfeeding. Mass spectrometry of fecal samples from B. infantis EVC001-fed infants showed that the resulting microbial community produced higher concentrations of lactate and acetate and lower excretion of HMO, while control infants showed significantly lower ability to capture and utilize these carbohydrates from human milk. Importantly, HMO content of breastmilk was not significantly different between groups and no difference was found in the gut microbiome of infants based on secretor status of mothers (presence or absence of 2'FL in breastmilk). Further, these changes were associated with reductions in taxa that have been associated with negative health outcomes including colic, asthma, eczema and allergy.

Conclusions: Overall, colonization with B. infantis is observed to be an effective way to restore maximal function of the infant gut microbiome to improve nutrient availability in the breastfed infant.

Funding Sources: This study was funded by Evolve BioSystems, Inc.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

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Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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