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21 May 2022 at 01:43
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Bibliography on: Fecal Transplantation


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RJR: Recommended Bibliography 21 May 2022 at 01:43 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2022-05-20

Bashir R, Wani IA, MA Ganie (2022)

Insights into new therapeutic approaches for the treatment and management of polycystic ovary syndrome: An updated review.

Current pharmaceutical design pii:CPD-EPUB-123741 [Epub ahead of print].

BACKGROUND: Polycystic ovary syndrome (PCOS) is a long-term, highly prevalent, complex heterogeneous, polygenic endocrine disorder characterized by both metabolic and reproductive disorders. It affects 6-23% of reproductive age women globally.

OBJECTIVE: This review aims to facilitate an understanding of novel PCOS management approaches and highlights the results from relevant interventional studies from animal and human studies.

METHODS: Manual search on PubMed, Cochrane, Scopus databases was performed for relevant articles, preclinical and clinical trials based on related keywords.

RESULTS: According to a multitude of studies, PCOS has evolved over time, but a substantial lag remains in management approaches. New insights into the cross-talk between muscle, brain, fat, and ovaries pointed out new therapeutic targets. This review has highlighted the efficacy of a wide spectrum of novel therapeutic agents [Phosphodiesterase-4 Inhibitors, Glucagon-like peptide-1 receptor agonists, nutritional supplements (Vitamins D and K, omega-3, prebiotics, probiotics and synbiotics), fecal microbiota transplantation (FMT) and intestinal cytokine IL-22] as PCOS therapeutic options. These novel therapies combine anti-inflammatory, insulin sensitizing, anti-obesity, and restoration of the gut microbiota and thus hold the potential to address the basic pathogenic mechanisms of PCOS.

CONCLUSION: Exhaustive, multicentric and multiethnic studies are vital to generate a network of normative data to better figure out the PCOS trajectory and change prognostic outcomes. Preclinical and clinical data is warranted to corroborate the new therapeutics and direct health care resources accordingly.

RevDate: 2022-05-19
CmpDate: 2022-05-19

Sorbara MT, EG Pamer (2022)

Microbiome-based therapeutics.

Nature reviews. Microbiology, 20(6):365-380.

Symbiotic microorganisms inhabiting the gastrointestinal tract promote health by decreasing susceptibility to infection and enhancing resistance to a range of diseases. In this Review, we discuss our increasing understanding of the impact of the microbiome on the mammalian host and recent efforts to culture and characterize intestinal symbiotic microorganisms that produce or modify metabolites that impact disease pathology. Manipulation of the intestinal microbiome has great potential to reduce the incidence and/or severity of a wide range of human conditions and diseases, and the biomedical research community now faces the challenge of translating our understanding of the microbiome into beneficial medical therapies. Our increasing understanding of symbiotic microbial species and the application of ecological principles and machine learning are providing exciting opportunities for microbiome-based therapeutics to progress from faecal microbiota transplantation to the administration of precisely defined and clinically validated symbiotic microbial consortia that optimize disease resistance.

RevDate: 2022-05-19

Bajaj JS, Ng SC, B Schnabl (2022)

Promises of microbiome-based therapies.

Journal of hepatology, 76(6):1379-1391.

Humans harbour large quantities of microbes, including bacteria, fungi, viruses and archaea, in the gut. Patients with liver disease exhibit changes in the intestinal microbiota and gut barrier dysfunction. Preclinical models demonstrate the importance of the gut microbiota in the pathogenesis of various liver diseases. In this review, we discuss how manipulation of the gut microbiota can be used as a novel treatment approach for liver disease. We summarise current data on untargeted approaches, including probiotics and faecal microbiota transplantation, and precision microbiome-centered therapies, including engineered bacteria, postbiotics and phages, for the treatment of liver diseases.

RevDate: 2022-05-19

Yan S, Chen J, Zhu L, et al (2022)

Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.

Journal of agricultural and food chemistry [Epub ahead of print].

Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.

RevDate: 2022-05-18

Yan J, Liao C, Taylor BP, et al (2022)

A compilation of fecal microbiome shotgun metagenomics from hematopoietic cell transplantation patients.

Scientific data, 9(1):219.

Hospitalized patients receiving hematopoietic cell transplants provide a unique opportunity to study the human gut microbiome. We previously compiled a large-scale longitudinal dataset of fecal microbiota and associated metadata, but we had limited that analysis to taxonomic composition of bacteria from 16S rRNA gene sequencing. Here we augment those data with shotgun metagenomics. The compilation amounts to a nested subset of 395 samples compiled from different studies at Memorial Sloan Kettering. Shotgun metagenomics describes the microbiome at the functional level, particularly in antimicrobial resistances and virulence factors. We provide accession numbers that link each sample to the paired-end sequencing files deposited in a public repository, which can be directly accessed by the online services of PATRIC to be analyzed without the users having to download or transfer the files. Then, we show how shotgun sequencing enables the assembly of genomes from metagenomic data. The new data, combined with the metadata published previously, enables new functional studies of the microbiomes of patients with cancer receiving bone marrow transplantation.

RevDate: 2022-05-19

Benech N, Galperine T, Sokol H, et al (2022)

SER-109 for Recurrent Clostridioides difficile Infection.

The New England journal of medicine, 386(20):1956-1957.

RevDate: 2022-05-17

Renu S, Deblais L, Patil V, et al (2022)

Gut Microbiota of Obese Children Influences Inflammatory Mucosal Immune Pathways in the Respiratory Tract to Influenza Virus Infection: Optimization of an Ideal Duration of Microbial Colonization in a Gnotobiotic Pig Model.

Microbiology spectrum [Epub ahead of print].

The impact of obesity on the human microbiota, immune maturation, and influenza virus infection has not been yet established in natural host animal models of influenza. In this study, gnotobiotic (Gn) pigs were colonized with human fecal microbiota (HFM) of obese (oHFM) or healthy lean (hHFM) children and infected at different periods (2-, 3-, and 5-weeks post-transplantation) using a zoonotic influenza virus strain. The infected oHFM pigs were characterized by lower levels of Firmicutes (Lactococcus, Lactobacillus, Turicibacter, and Streptococcus) and Actinobacteria (Bifidobacterium), which was associated with higher levels of Proteobacteria (Klebsiella), Bacteroidetes, and Verrucomicrobia (Akkermansia) compared with the infected hHFM group (P < 0.01). Furthermore, these genera significantly correlated with the expression of immune effectors, immune regulators, and inflammatory mediators, and displayed opposite trends between oHFM and hHFM groups (P < 0.01). The lymphoid and myeloid immune cell frequencies were differently modulated by the oHFM and hHFM colonization, especially apparent in the 5-weeks HFM colonized piglets. In addition, oHFM group had higher pro-inflammatory cytokines (IL-6, IL-12, TNF-α, and IFNγ) gene expression in the respiratory tract compared with the hHFM colonized pigs was detected. In conclusion, pigs colonized for longer duration, established oHFM increased the immune maturation favoring the activation of inflammatory mediators, however, the influenza virus load remained comparable with the hHFM group. Further, a longer duration of microbial colonization (5 weeks) may be required to reveal the impact of microbiome on the host immune maturation and susceptibility to influenza virus infection in the humanized Gn pig model. IMPORTANCE The diversity of gut microbiome of obese people differs markedly from that of lean healthy individuals which, in turn, influences the severity of inflammatory diseases because of differential maturation of immune system. The mouse model provides crucial insights into the mechanism(s) regulating the immune systems mediated by the gut microbiota but its applicability to humans is questionable because immune cells in mice are poorly activated in microbiota humanized mice. Several important strains of Bifidobacterium, Lactobacillus, and Clostridium fails to colonize the murine gut. Thus, understanding the role of certain important commensal gut bacterial species influences upon health and disease, a suitable large animal model like pig that supports the growth and colonization of most of the important human gut bacteria and possess comparable immunology and physiology to humans is beneficial to improve health.

RevDate: 2022-05-16

Piawah S, Walker EJ, Van Blarigan EL, et al (2022)

The Gut Microbiome in Colorectal Cancer.

Hematology/oncology clinics of North America pii:S0889-8588(22)00012-0 [Epub ahead of print].

The gut microbiome is important in human health and disease. Recent studies have begun to elucidate its specific role in colorectal cancer. The gut microbiome seems to play an integral role in colorectal cancer initiation and progression, and oncologic drug metabolism and toxicity. This review examines the associations between the gut microbiome and colorectal cancer initiation, progression, and oncologic drug metabolism, highlighting proposed mechanisms and landmark publications in this field. It also discusses potential methods of modulating the gut microbiome, underscoring the gaps in current understanding, and ends with a clinically relevant overview of microbiome research considerations and study design.

RevDate: 2022-05-16

Yan Y, Peng X, Y Chen (2022)

[Fecal microbiota transplantation in the treatment of acute intestinal pseudo obstruction secondary to intracerebral hemorrhage: a case report and literature review].

Zhonghua wei zhong bing ji jiu yi xue, 34(3):306-310.

OBJECTIVE: To analyze the clinical effects of fecal microbiota transplantation (FMT) on the treatment of acute intestinal pseudo obstruction (AIPO) secondary to intracerebral hemorrhage.

METHODS: The clinical data of a patient with AIPO secondary to intracerebral hemorrhage who was admitted to Nanfang Hospital of Southern Medical University was analyzed. The flora compositon between donor and patient was compared, finding the changes of intestinal flora before and after FMT (day 0 and day 25).

RESULTS: The main clinical findings in the patient were serious bloating, expansion of the intestinal canal and intra-abdominal hypertension. A week of conventional therapy was not effective, and the symptoms became progressively worse, affecting respiratory function.The result of fecal flora suggested the intestinal microbiota dybiosis, so FMT was attempted. After FMT, the patient's gastrointestinal symptoms were significantly relieved, and there were no further episodes within 25 days. The new result of fecal flora showed that the flora colonizing the intestine was dominated by Akkermansia and Bifidobacterium, with a significant decrease in potential pro-inflammatory and gas-producing bacteria and an increased gut microbiota diversity. The results trended to be partly consistent with the donor at 25 days after FMT: at the phylum level, the relative abundance of Bacterioidetes, Vereucomicrobia, Firmicutes and Actinobacteria were increased while Proteobacteria was decreased; at the class level, the relative abundance of Verrucomicrobiae, Bacterioidia, Actinobacteria, Coriobacteriia and Clostridia were increased and Gammaproteobacteria was decreased; at the order level, the relative abundance of Bacterioidales, Verrucomicrobiales, Clostridiale, Coriobacteriales were increased and Betaproteobacteriales, Enterobacteriales were decreased; at the family level, the relative abundance of Bifidobacteriaceae, Akkermansiaceae, Ruminococcaceae were increased and Enterobacteriaceae was decreased; at the genus level, the relative abundance of Akkermansia, Bifidobacterium were increased and Escherichia-Shigella, Klebsiella were decreased. At 1-year follow-up, the patient lived with self-care and scored 5 points in Glasgow outcome scale (GOS).

CONCLUSIONS: FMT may provide clinical benefit in treated patients with AIPO secondary to intracerebral hemorrhage, probably by regulating the intestinal microflora, and re-establishing proper intestinal barrier, to maintain intestinal homeostasis.

RevDate: 2022-05-16

Zhao H, Lyu Y, Zhai R, et al (2022)

Metformin Mitigates Sepsis-Related Neuroinflammation via Modulating Gut Microbiota and Metabolites.

Frontiers in immunology, 13:797312.

Gut microbiota affects the functions of brains. However, its mechanism in sepsis remains unclear. This study evaluated the effect of metformin on ameliorating sepsis-related neurodamage by regulating gut microbiota and metabolites in septic rats. Cecal ligation and puncture (CLP) was used to establish the sepsis-related neurodamage animal models. Metformin therapy by gavage at 1 h after CLP administration was followed by fecal microbiota transplantation (FMT) to ensure the efficacy and safety of metformin on the sepsis-related neurodamage by regulating gut microbiota. The gut microbiota and metabolites were conducted by 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry metabolomic analysis. The brain tissue inflammation response was analyzed by histopathology and reverse transcription-polymerase chain reaction (RT-PCR). This study reported brain inflammatory response, hemorrhage in sepsis-related neurodamage rats compared with the control group (C group). Surprisingly, the abundance of gut microbiota slightly increased in sepsis-related neurodamage rats than C group. The ratio of Firmicutes/Bacteroidetes was significantly increased in the CLP group than the C group. However, no difference was observed between the CLP and the metformin-treated rats (MET group). Interestingly, the abundance of Escherichia_Shigella increased in the MET group than the C and CLP groups, while Lactobacillaceae abundance decreased. Furthermore, Prevotella_9, Muribaculaceae, and Alloprevotella related to short-chain fatty acids production increased in the sepsis-related neurodamage of metformin-treated rats. Additionally, Prevotella_9 and Muribaculaceae correlated positively to 29 metabolites that might affect the inflammatory factors in the brain. The FMT assay showed that metformin improved sepsis-related neurodamage by regulating the gut microbiota and metabolites in septic rats. The findings suggest that metformin improves the sepsis-related neurodamage through modulating the gut microbiota and metabolites in septic rats, which may be an effective therapy for patients with sepsis-related neurodamage.

RevDate: 2022-05-16

Kawasoe J, Uchida Y, Kawamoto H, et al (2022)

Propionic Acid, Induced in Gut by an Inulin Diet, Suppresses Inflammation and Ameliorates Liver Ischemia and Reperfusion Injury in Mice.

Frontiers in immunology, 13:862503.

Liver ischemia and reperfusion injury (IRI) is one of the obstacles in liver surgery such as liver resection and transplantation. In this study, we investigated the preventive effect on mouse liver IRI by feeding mice with inulin, which is a heterogeneous blend of indigestible fructose polymer. Mice were fed either a control ordinary diet (CD) or an inulin diet (ID) containing 5% inulin in the CD, for 14 days before the ischemia and reperfusion (IR) maneuver. IR induced-liver damages were significantly ameliorated in the ID group, compared with those in the CD group. Feeding mice with an ID, but not a CD, elevated levels of Bacteroidetes among gut microbiota, and especially increased Bacteroides acidifaciens in mouse feces, which resulted in significant elevation of short-chain fatty acids (SCFAs) in the portal vein of mice. Among SCFAs, propionic acid (PA) was most significantly increased. The microbial gene functions related to PA biosynthesis were much higher in the fecal microbiome of the ID group compared to the CD. However, the action of PA on liver IRI has not been yet clarified. Direct intraperitoneal administration of PA alone prior to the ischemia strongly suppressed liver cell damages as well as inflammatory responses caused by liver IR. Furthermore, PA suppressed the secretion of inflammatory cytokines from peritoneal macrophages stimulated in vitro through TLR-4 with high-mobility group box 1 protein (HMGB-1), known to be released from apoptotic liver cells during the IR insult. The present study shows that PA may play a key role in the inulin-induced amelioration of mouse liver IRI.

RevDate: 2022-05-16

Al KF, Craven LJ, Gibbons S, et al (2022)

Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.

Multiple sclerosis journal - experimental, translational and clinical, 8(2):20552173221086662 pii:10.1177_20552173221086662.

Background: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease.

Objective: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability.

Methods: Nine patients with MS were recruited and provided monthly FMTs for up to six months. The primary outcome investigated was change in peripheral blood cytokine concentrations. The secondary outcomes were gut microbiota composition, intestinal permeability, and safety (assessed with EDSS and MRI).

Results: The study was terminated early and was subsequently underpowered to assess whether peripheral blood cytokines were altered following FMTs. FMTs were safe in this group of patients. Two of five patients had elevated small intestinal permeability at baseline that improved to normal values following FMTs. Significant, donor-specific, beneficial alterations to the MS patient gut microbiota were observed following FMT.

Conclusion: FMT was safe and tolerable in this cohort of RRMS patients, may improve elevated small intestinal permeability, and has the potential to enrich for an MS-protective microbiota. Further studies with longer follow-up and larger sample sizes are required to determine if FMT is a suitable therapy for MS.

RevDate: 2022-05-14

Chatterjee G, Negi S, Basu S, et al (2022)

Microbiome systems biology advancements for natural well-being.

The Science of the total environment pii:S0048-9697(22)03012-1 [Epub ahead of print].

Over the course of years all data from epidemiological, physiological and omics have suggested that the microbial communities play a considerable role in modulating human health. These set of microorganisms residing in the human intestine collectively known as microbiota presents a genetic repertoire that is higher in magnitude than the human genome. They play an essential role in host immunity and neuronal signaling. Rapid enhancement of sequence based screening and humanized gnotobiotic model has sparked a great deal of interest among scientists to interact the dynamic interactions of the commensal bacteria. This review focuses on systemic analysis of the gut microbiome to decipher the complexity of the host-microbe intercommunication and gives a special emphasis on the evolution of targeted precision medicine through microbiome engineering. In addition, we have also provided a comprehensive understanding of how interconnection between metabolism and biochemical reactions in a specific organism can be obtained from a metabolic network or a flux balance analysis and can help in the identification of a particular metabolite, by combining multiple datasets. The review highlights on how the genetic modification of the critical components and programming the resident microflora can be employed for targeted precision medicine. Inspite of the ongoing debate on the utility of gut microbiome we have explored on the probable new therapeutic avenues like FMT (Fecal microbiota transplant) can be utilized. This review also recapitulates integrating human-relevant 3D cellular models coupled with computational models and the metadata obtained from interventional and epidemiological studies may decipher the complex interactome of diet-microbiota-disease pathophysiology. In addition, it will also open new avenues for the development of therapeutics derived from microbiome or implementation of personalized nutrition. In addition, the identification of biomarkers can also help towards the development of new diagnostic tools and eventually will lead to strategic management of the disease.

RevDate: 2022-05-14

Fan Z, Zhang X, Shang Y, et al (2022)

Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries.

International journal of molecular sciences, 23(9): pii:ijms23094797.

Obesity induced by a high-fat diet (HFD) leads to the excessive consumption of primordial follicles (PFs) in the ovaries. There is systemic chronic inflammation under HFD conditions, but no previous studies have explored whether there is a certain causal relationship between HFD-induced chronic inflammation and the overactivation of PFs. Here, we showed that HFD causes disorders of intestinal microflora in mice, with five Gram-negative bacteria showing the most profound increase at the genus level compared to the normal diet (ND) groups and contributes to the production of endotoxin. Endotoxin promotes M1 macrophage infiltration in the ovaries, where they exhibit proinflammatory actions by secreting cytokines IL-6, IL-8, and TNFα. These cytokines then boost the activation of PFs by activating Signal Transducer and Activator of Transcription 3 (STAT3) signaling in follicles. Interestingly, transplantation of the HFD intestinal microflora to the ND mice partly replicates ovarian macrophage infiltration, proinflammation, and the overactivation of PFs. Conversely, transplanting the ND fecal microbiota to the HFD mice can alleviate ovarian inflammation and rescue the excessive consumption of PFs. Our findings uncover a novel and critical function of gut microbes in the process of PF overactivation under HFD conditions, and may provide a new theoretical basis for the microbial treatment of patients with premature ovarian insufficiency caused by HFD.

RevDate: 2022-05-14

Soriano S, Curry K, Wang Q, et al (2022)

Fecal Microbiota Transplantation Derived from Alzheimer's Disease Mice Worsens Brain Trauma Outcomes in Wild-Type Controls.

International journal of molecular sciences, 23(9): pii:ijms23094476.

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration, both of which increase the risk and accelerate the progression of Alzheimer's disease (AD). The gut microbiome is an essential modulator of the immune system, impacting the brain. AD has been related with reduced diversity and alterations in the community composition of the gut microbiota. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in control mice. We prepared fecal microbiota transplants from 18 to 24 month old 3×Tg-AD (FMT-AD) and from healthy control (FMT-young) mice. FMTs were administered orally to young control C57BL/6 (wild-type, WT) mice after they underwent controlled cortical impact (CCI) injury, as a model of TBI. Then, we characterized the microbiota composition of the fecal samples by full-length 16S rRNA gene sequencing analysis. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD administration stimulates a higher relative abundance of the genus Muribaculum and a decrease in Lactobacillus johnsonii compared to FMT-young in WT mice. Furthermore, WT mice exhibited larger lesion, increased activated microglia/macrophages, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. In summary, we observed gut microbiota from AD mice to have a detrimental effect and aggravate the neuroinflammatory response and neurological outcomes after TBI in young WT mice.

RevDate: 2022-05-13

Wang X, Wu X, Cong X, et al (2022)

The functional role of fecal microbiota transplantation on Salmonella Enteritidis infection in chicks.

Veterinary microbiology, 269:109449 pii:S0378-1135(22)00119-5 [Epub ahead of print].

The intestinal microbiota plays important roles in animal health and growth. We investigated the efficacy and mechanisms of fecal microbiota transplantation (FMT) from adult SPF chickens against Salmonella Enteritidis (SE) infection in chicks. We transplanted 160 recipient SPF chicks (1-day-old) that were randomly divided into four groups, Ca (challenge), Cb (non-challenge), Fa (FMT and challenge) and Fb (FMT without challenge). The experiment lasted 40 days. We found that FMT reduced mortality as well as liver inflammatory lesions, promoted weight gain, improved immunity, ameliorated the digestion and absorption ability and inhibited SE colonization in the liver of challenged chicks. 16S rRNA gene high-throughput sequencing indicated that SE challenge caused a significant increase in the relative abundance of Parasutterella in the cecal microbiota of the recipient chicks (P < 0.05). FMT led to the maturation of the intestinal flora of recipients and the relative abundance of the Bacteroides, Rikenellaceae_ RC9_ gut_ group, Prevotellaceae_ UCG_ 001, Prevotellaceae_ Ga6A1_ group and Parabacteroides was significantly increased (P < 0.05). FMT from adult SPF chickens regulated the intestinal microbiota of chicks and increased resistance to SE infection.

RevDate: 2022-05-13

Hermanson JB, Fei N, Miyoshi S, et al (2022)

Dietary Cholesterol-Induced Gut Microbes Drive Nonalcoholic Fatty Liver Disease Pathogenesis in a Murine Model.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36 Suppl 1:.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of metabolic syndrome and major indications for liver transplantation. Western diet contributes to disease pathogenesis, partially mediated through the gut microbiome, yet mechanisms remain elusive. Human epidemiological studies identified high dietary cholesterol intake as a NAFLD risk factor and it is essential to drive disease in murine models, yet little is known about its role in reshaping gut microbiota. Using the fast food (FF) diet murine model in germ-free (GF) mice completely devoid of all microbes and their conventionally-raised (control) counterparts harboring complex microbiomes, we hypothesized high dietary cholesterol-induced gut microbiota impact NAFLD onset, progression, and severity. Male C57Bl/6 age-matched GF and control mice were fed 1 of 4 semi-purified diets: low-fat (LF); high fat (HF); FF + 0.2% high cholesterol (FFHC); FF + 2% very high cholesterol (FFVHC) for 8 or 24 weeks. Fecal gut microbiota profiles were tracked over time via Illumina MiSeq 16S rRNA gene amplicon sequencing. Serum alanine transaminase (ALT) and lipopolysaccharide binding protein (LBP, an indicator of gut barrier function) were measured throughout the study. Livers were collected for histology and Illumina NovaSeq RNA-sequencing. Despite equal caloric intake between GF and controls across diets, significant weight gain and increased liver weight to body weight ratios (P<0.05) were observed only in control mice fed FF diets. GF mice were largely protected from disease, with no elevation in plasma ALT, LBP, or histology-based NAFLD activity score (NAS) regardless of treatment. Conversely, FFVHC control mice exhibited significantly elevated plasma ALT after 8 weeks on diet, which was exacerbated at 24 weeks relative to LF control and all GF groups. FF diets significantly increased (FFHC: P<0.05; FFVHC: P<0.01) plasma LBP after 24 weeks. Control mice fed FF diets exhibited severe steatosis, where FFVHC significantly increased NAS at 8 (P<0.05) and 24 (P<0.001) weeks relative to LF control and all GF groups. Microbiota profiling revealed no change in α-diversity regardless of diet in control mice. β-diversity analysis showed HF and FF diets, particularly FFVHC, rapidly shifted gut microbiota community membership after only 4 weeks, preceding disease onset and was further exacerbated over time. Liver RNA-seq revealed FFVHC diet in control, but not GF, mice significantly enriched genes involved in the KEGG pathway, "antigen processing and presentation" (Bonferroni P<0.001) relative to HF-fed counterparts at 24 weeks. Taken together, FF diet-induced shifts in gut microbes are both a prerequisite for and precede NAFLD/NASH disease onset, which is exacerbated by increased dietary cholesterol, driving liver inflammation. These data provide unique insights into how Western diet components impact host-microbe interactions in complex liver diseases, which may aid in identifying novel therapeutic interventions.

RevDate: 2022-05-13

Inczefi O, Bacsur P, Resál T, et al (2022)

The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease.

Frontiers in nutrition, 9:718710.

The leakage of the intestinal barrier and the disruption of the gut microbiome are increasingly recognized as key factors in different pathophysiological conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), chronic liver diseases, obesity, diabetes mellitus, types of cancer, and neuropsychiatric disorders. In this study, the mechanisms leading to dysbiosis and "leaky gut" are reviewed, and a short summary of the current knowledge regarding different diseases is provided. The simplest way to restore intestinal permeability and the microbiota could be ideal nutrition. Further therapeutic options are also available, such as the administration of probiotics or postbiotics or fecal microbiota transplantation.

RevDate: 2022-05-13

Lei J, Dong Y, Hou Q, et al (2022)

Intestinal Microbiota Regulate Certain Meat Quality Parameters in Chicken.

Frontiers in nutrition, 9:747705.

Growing evidence of intestinal microbiota-muscle axis provides a possibility to improve meat quality of broilers through regulating intestinal microbiota. Water-holding capacity is a crucial factor to evaluate the meat quality. High quality of water-holding capacity is usually described as a low drip-losing rate. This study aimed to explore the relationship between intestinal microbiota and water-holding capacity of muscle in broilers. According to our results, two native breeds of broilers (the Arbor Acres broilers and the Beijing-You broilers) exhibited remarkable differences in microbiota composition. However, the regular of gut bacteria compositions gradually became similar when the two breeds of broiler were raised in a same feeding environment. Therefore, this similar regular of intestinal microbiota induced similar water-holding capacity of the muscle from the two breeds. In subsequent fecal microbiota transplantation (FMT) experiments, the intestinal microbiota community of the Arbor Acres broilers was remodeling by oral gavage of bacterial suspension that was derived from the Beijing-You broilers. Then, not only body weight and abdominal fat rate were increased, but also drip loss of muscle was decreased in the Arbor Acres broilers. Additionally, muscle fiber diameter of biceps femoris muscle and expression of MyoD1 were notably enlarged. Muscle fiber diameter and related genes were deemed as important elements for water-holding capacity of muscle. Simultaneously, we screened typical intestinal bacteria in both the two native breeds of broilers by 16S rDNA sequencing. Lachnoclostridium was the only bacteria genus associated with drip-losing rate, meat fiber diameter, body weight, and abdominal fat rate.

Importance: Higher body weight and superior meat quality in livestock imply an adequate source of protein and substantial commercial value. Regulating the intestinal microbiota of broilers is a promising approach to optimize commercial phenotypes. Our results indicate that the intestinal microbiota profile could be reconstructed by external factors, leading to advantageous changes in muscle characteristics. The cecum microbiota of native broilers have the ability to improve certain meat quality and production performance. The population of Lachnoclostridium spp. could be used to regulate body weight and drip-losing rate in broilers, but more study is needed.

RevDate: 2022-05-11

Ouyang ZR, Niu XR, Wang WG, et al (2022)

The role of short-chain fatty acids in Clostridioides difficile infection: A review.

Anaerobe pii:S1075-9964(22)00073-7 [Epub ahead of print].

Clostridioides difficile is a Gram-positive, obligate anaerobic, spore-producing intestinal opportunistic pathogen. CDI outbreaks in Europe and the Americas in recent years are a major health concern. Intestinal short-chain fatty acids (SCFAs) are an important energy source for colonic epithelial cells, and the roles of SCFAs in reducing intestinal inflammation, inhibiting intestinal tumours, and regulating gut microbial homeostasis are being actively researched. Furthermore, SCFAs attenuate CDI or directly inhibit C. difficile growth through different pathways in vivo and in vitro. This review assesses the role of SCFAs in CDI and discusses the potential use of these molecules as therapeutic targets for CDI.

RevDate: 2022-05-11

Diao H, Yan HL, Xiao Y, et al (2018)

Modulation of intestine development by fecal microbiota transplantation in suckling pigs.

RSC advances, 8(16):8709-8720 pii:c7ra11234c.

The present study was conducted to investigate the effects of early fecal microbiota transplantation on gut development in sucking piglets. A total of 24 3 day-old DLY sucking piglets (2.11 ± 0.15) kg were randomly divided into four groups (TMP, YMP, RMP and control group (CON)), which were transplanted with intact fecal microbiota of Tibetan pig (TP), Yorkshire pig (YP), Rongchang pig (RP), and without transplantation, respectively. The whole trial lasted for 56 d. The results are as follows: when compared with the YMP and RMP treatments, TMP and CON had a lower diarrhea index (P < 0.05), TMP and CON had higher GLP-2 and ANG4 mRNA abundances in the ileum (P < 0.05), and the TMP had a higher jejunal villus height: crypt depth and a higher colonic GLP-2 mRNA abundance (P < 0.05). Moreover, when compared with the YMP and RMP treatments, TMP had an enhanced DMT1 mRNA abundance in the duodenum (P < 0.05), TMP and CON had a greater lactase activity and a higher DMT1 mRNA abundance in the jejunum (P < 0.05), and CON had a higher γ-GT activity in the jejunum (P < 0.05). The jejunal Ca2+, Mg2+-ATPase activity in TMP was higher than that in CON, and the jejunal Na+, K+-ATPase activity in TMP was higher than that in the other three treatments (P < 0.05). Besides, when compared with the YMP and RMP treatments, TMP had a lower MDA content and a higher MUC1 mRNA abundance in the jejunum (P < 0.05); CON had a higher SOD activity in the jejunum (P < 0.05), whereas TMP and CON had a higher butyric acid concentration in the colon and a lower LPS content in the serum (P < 0.05). Finally, when compared with the TMP treatment, the other three treatments had an enhanced IL-10 mRNA abundance in the colon (P < 0.05), YMP and CON had higher counts of Escherichia coli in the colonic digesta (P < 0.05), and the CON had lower counts of Lactobacillus spp in the cecal and colonic digesta (P < 0.05). These data indicated that early transplantation of the fecal microbiota from the Yorkshire pigs and Rongchang pigs to DLY suckling piglets would destroy the gut microbiota balance and thus damage intestinal health.

RevDate: 2022-05-10

Shin J, Noh JR, Choe D, et al (2022)

Comprehensive 16S rRNA and metagenomic data from the gut microbiome of aging and rejuvenation mouse models.

Scientific data, 9(1):197.

The gut microbiota is associated with the health and longevity of the host. A few methods, such as fecal microbiota transplantation and oral administration of probiotics, have been applied to alter the gut microbiome and promote healthy aging. The changes in host microbiomes still remain poorly understood. Here, we characterized both the changes in gut microbial communities and their functional potential derived from colon samples in mouse models during aging. We achieved this through four procedures including co-housing, serum injection, parabiosis, and oral administration of Akkermansia muciniphila as probiotics using bacterial 16 S rRNA sequencing and shotgun metagenomic sequencing. The dataset comprised 16 S rRNA sequencing (36,249,200 paired-end reads, 107 sequencing data) and metagenomic sequencing data (307,194,369 paired-end reads, 109 sequencing data), characterizing the taxonomy of bacterial communities and their functional potential during aging and rejuvenation. The generated data expand the resources of the gut microbiome related to aging and rejuvenation and provide a useful dataset for research on developing therapeutic strategies to achieve healthy active aging.

RevDate: 2022-05-10

Alsegiani AS, ZA Shah (2022)

The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline.

Neural regeneration research, 17(11):2407-2412.

Recent emerging research on intestinal microbiota and its contribution to the central nervous system during health and disease has attracted significant attention. Age-related intestinal microbiota changes initiate brain aging and age-related neurodegenerative disorders. Aging is one of the critical predisposing risk factors for the development of neurodegenerative diseases. Maintaining a healthy gut microbiota is essential for a healthy body and aging, but dysbiosis could initiate many chronic diseases. Understanding the underlying mechanisms of gut microbiota alterations/dysbiosis will help identify biomarkers for aging-related chronic conditions. This review summarizes recent advances in microbiota-neurodegenerative disease research and will enhance our understanding of gut microbiota dysbiosis and its effects on brain aging.

RevDate: 2022-05-10

Philips CA, P Augustine (2022)

Gut Barrier and Microbiota in Cirrhosis.

Journal of clinical and experimental hepatology, 12(2):625-638.

Gut microbiota and their homeostatic functions are central to the maintenance of the intestinal mucosal barrier. The gut barrier functions as a structural, biological, and immunological barrier, preventing local and systemic invasion and inflammation of pathogenic taxa, resulting in the propagation or causation of organ-specific (liver disease) or systemic diseases (sepsis) in the host. In health, commensal bacteria are involved in regulating pathogenic bacteria, sinister bacterial products, and antigens; and help control and kill pathogenic organisms by secreting antimicrobial metabolites. Gut microbiota also participates in the extraction, synthesis, and absorption of nutrient metabolites, maintains intestinal epithelial integrity and regulates the development, homeostasis, and function of innate and adaptive immune cells. Cirrhosis is associated with local and systemic immune, vascular, and inflammatory changes directly or indirectly linked to perturbations in quality and quantity of intestinal microbiota and intestinal mucosal integrity. Dysbiosis and gut barrier dysfunction are directly involved in the pathogenesis of compensated cirrhosis and the type and severity of complications in decompensated cirrhosis, such as bacterial infections, encephalopathy, extrahepatic organ failure, and progression to acute on chronic liver failure. This paper reviews the normal gut barrier, gut barrier dysfunction, and dysbiosis-associated clinical events in patients with cirrhosis. The role of dietary interventions, antibiotics, prebiotics, probiotics, synbiotics, and healthy donor fecal microbiota transplantation (FMT) to modulate the gut microbiota for improving patient outcomes is further discussed.

RevDate: 2022-05-09

Alabdaljabar MS, Aslam HM, Veeraballi S, et al (2022)

Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease.

Cureus, 14(4):e23873.

A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.

RevDate: 2022-05-09

Lai Z, Chen Z, Zhang A, et al (2022)

The Gut Microbiota in Liver Transplantation Recipients During the Perioperative Period.

Frontiers in physiology, 13:854017 pii:854017.

Background: Chronic liver disease is a global problem, and an increasing number of patients receive a liver transplant yearly. The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients during the perioperative. Methods: We studied gut fecal microbial community signatures in 37 Chinese adults using 16S rRNA sequencing targeting V3-V4 hypervariable regions, with a total of 69 fecal samples. We analyzed the Alpha and Beta diversities of various groups. Then we compared the abundance of bacteria in groups at the phylum, family, and genus levels. Results: The healthy gut microbiota predominantly consisted of the phyla Firmicutes and Bacteroidestes, followed by Proteobacteria and Actinobacteria. Compared with healthy people, due to the dominant bacteria in patients with chronic liver disease losing their advantages in the gut, the antagonistic effect on the inferior bacteria was reduced. The inferior bacteria multiplied in large numbers during this process. Some of these significant changes were observed in bacterial species belonging to Enterococcus, Klebsiella, and Enterobacter, which increased in patients' intestines. There were low abundances of signature genes such as Bacteroides, Prevotella, and Ruminococcus. Blautia and Bifidobacterium (considered probiotics) almost disappeared after liver transplantation. Conclusion: There is an altered microbial composition in liver transplantation patients and a distinct signature of microbiota associated with the perioperative period.

RevDate: 2022-05-09

Liang F, Lu X, Deng Z, et al (2022)

Effect of Washed Microbiota Transplantation on Patients With Dyslipidemia in South China.

Frontiers in endocrinology, 13:827107.

Background and Aims: Although the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population.

Methods: Clinical data of patients with various indications who received WMT for 1-3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared.

Results: A total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p <0.05). Hyper blood lipid decreased to normal in the short-term (35.14%; p <0.001), and LDL-C changed to normal in the medium term (33.33%; p = 0.013). In the hypolipidemia group, 36.36% and 47.06% changed to normal in the short-term (p = 0.006) and medium term (p = 0.005) of therapeutic effects based on blood lipid levels. In the normal blood lipid group and the low-risk group of atherosclerotic cardiovascular disease (ASCVD), the change was not statistically significant, indicating that WMT does not increase the risk of blood lipid and ASCVD in the long-term.

Conclusions: WMT treatment changes blood lipids in patients with hyperlipidemia and hypolipidemia without serious adverse events, with no risk for increasing blood lipids and ASCVD in the long-term. There were significant decreased TC, TG, and LDL-C levels in the medium term of WMT treatment for hyperlipidemia. Therefore, the regulation of gut microbiota by WMT may indicate a new clinical method for the treatment of dyslipidemia.

RevDate: 2022-05-08

Kinoshita Y, Niwa H, Uchida-Fujii E, et al (2022)

Simultaneous daily fecal microbiota transplantation fails to prevent metronidazole-induced dysbiosis of equine gut microbiota.

Journal of equine veterinary science pii:S0737-0806(22)00142-3 [Epub ahead of print].

Antimicrobial administration can lead to imbalances of gastrointestinal microbiota, called dysbiosis. Dysbiosis sometimes results in diarrhea and enteritis in horses. Fecal microbiota transplantation (FMT) is used to treat affected horses, but whether it is effective as a prophylactic approach for dysbiosis in horses receiving antimicrobials remains unknown. The aim of this study was to assess the efficacy of simultaneous FMT against metronidazole-induced dysbiosis in horses. Changes in the ratios of bacterial families, determined by metagenomic analysis, were similar between the metronidazole-treated group and the simultaneous metronidazole- and FMT-treated group, notably in the Clostridiaceae, Ruminococcaceae, and Enterobacteriaceae. Differences in fecal bacterial compositions were due mainly to metronidazole administration (P = 0.0003), but not to FMT (P = 0.3136). Simultaneous FMT at 500 g of donor feces in 1 L of suspension once a day did not inhibit metronidazole-induced dysbiosis. The results show that the FMT protocol needs to be improved to prevent metronidazole-induced gut dysbiosis in horses.

RevDate: 2022-05-09
CmpDate: 2022-05-09

Crits-Christoph A, Hallowell HA, Koutouvalis K, et al (2022)

Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome.

Gut microbes, 14(1):2055944.

A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.

RevDate: 2022-05-09
CmpDate: 2022-05-09

Ng SC, Xu Z, Mak JWY, et al (2022)

Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.

Gut, 71(4):716-723.

OBJECTIVE: The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).

DESIGN: In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.

RESULTS: Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).

CONCLUSION: Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness.


RevDate: 2022-05-07

Ianiro G (2022)

An artificial microbiome consortium prevents recurrence of C. difficile infection: paving the way for fecal microbiota transplantation 2.0.

Gastroenterology pii:S0016-5085(22)00470-X [Epub ahead of print].

RevDate: 2022-05-06

Liu D, Zhao R, Wu Y, et al (2022)

Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis.

Frontiers in pharmacology, 13:819851 pii:819851.

Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1β, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.

RevDate: 2022-05-05

Cheng F, Huang Z, Li Z, et al (2022)

Efficacy and safety of fecal microbiota transplant for recurrent Clostridium difficile infection in inflammatory bowel disease patients: a systematic review and meta-analysis.

Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva [Epub ahead of print].

OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate the outcomes of fecal microbiota transplantation (FMT) therapy for recurrent Clostridium difficile infection (C) among inflammatory bowel disease (IBD) patients.

METHODS: Electronic databases were searched for studies that reported efficacy and/or safety of FMT therapy for recurrent CDI among IBD. We used the meta-prop command of the meta package in R to assess the efficacy and safety. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.

RESULTS: 11 trials were included in our study. Pooled analysis showed that the initial cure rate of recurrent CDI among IBD patients was 80% (95% CI 0.76, 0.84), and the overall cure rate after two or more FMT procedures was 90% (95% CI 0.84, 0.94). The recurrence rate post FMT therapy was 25% (95% CI: 0.20, 0.32). Sub-analyses suggested that the initial cure rate of CDI in ulcerative colitis (UC) patients was higher than that in Crohn's disease (CD) patients (85% vs. 79%), with no statistically significant differences (P >0.05). No serious adverse events were noted in any of the patients post-FMT.

CONCLUSIONS: FMT is an effective and safe treatment for recurrent CDI in patients with IBD. FMT should be considered early in cases of recurrent or refractory CDI. Multiple FMT procedures can improve the cure rate of CDI.

RevDate: 2022-05-04

Oliveira AC, Yang T, Li J, et al (2022)

Fecal matter transplant from Ace2 overexpressing mice counteracts chronic hypoxia-induced pulmonary hypertension.

Pulmonary circulation, 12(1):e12015 pii:PUL212015.

Recent evidence suggests pulmonary hypertension (PH), a disease of the pulmonary vasculature actually has multiorgan pathophysiology and perhaps etiology. Herein, we demonstrated that fecal matter transplantation from angiotensin-converting enzyme 2 overexpressing mice counteracted the effects of chronic hypoxia to prevent pulmonary hypertension, neuroinflammation, and gut dysbiosis in wild type recipients.

RevDate: 2022-05-03

Parker A, Romano S, Ansorge R, et al (2022)

Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain.

Microbiome, 10(1):68.

BACKGROUND: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.

METHODS: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing.

RESULTS: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.

CONCLUSIONS: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut-brain and gut-retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. Video abstract.

RevDate: 2022-05-03
CmpDate: 2022-05-03

Xing J, Liao Y, Zhang H, et al (2022)

Impacts of MicroRNAs Induced by the Gut Microbiome on Regulating the Development of Colorectal Cancer.

Frontiers in cellular and infection microbiology, 12:804689.

Although a dysfunctional gut microbiome is strongly linked to colorectal cancer (CRC), our knowledge of the mediators between CRC and the microbiome is limited. MicroRNAs (miRNAs) affect critical cellular processes, such as apoptosis, proliferation, and differentiation, and contribute to the regulation of CRC progression. Increasingly, studies found that miRNAs can significantly mediate bidirectional interactions between the host and the microbiome. Notably, miRNA expression is regulated by the gut microbiome, which subsequently affects the host transcriptome, thereby influencing the development of CRC. This study typically focuses on the specific functions of the microbiome in CRC and their effect on CRC-related miRNA production and reviews the role of several bacteria on miRNA, including Fusobacterium nucleatum, Escherichia coli, enterotoxigenic Bacteroides fragilis, and Faecalibacterium prausnitzii. Based on the important roles of miRNAs and the gut microbiome in CRC, strategies for modulating miRNA expression and regulating the gut microbiome composition need to be applied, such as bioactive dietary components and fecal microorganism transplantation.

RevDate: 2022-05-02

Li X, Zhao W, Xiao M, et al (2022)

Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice.

Journal of ethnopharmacology pii:S0378-8741(22)00372-5 [Epub ahead of print].

Penthorum chinense Pursh. (PCP) is commonly used as a Miao ethno-medicine and health food for liver protection in China. Gansukeli (WS3-B-2526-97) is made from the extract of PCP (PCPE) for the treatment of viral hepatitis. In recent years, PCPE has been reported in the treatment of non-alcoholic fatty liver disease (NAFLD), however its potential mechanism is not fully elucidated.

AIM OF THE STUDY: To investigate the ameliorating effect of PCPE on high-fat diet (HFD)-induced NAFLD mice and demonstrate whether its protective effect is gut microbiota dependent and associated with bile acid (BA) metabolism.

MATERIALS AND METHODS: The alleviating effect of PCPE on NAFLD was conducted on male C57BL/6J mice fed an HFD for 16 weeks, and this effect associated with gut microbiota dependent was demonstrated by pseudo-germfree mice treated with antibiotics and fecal microbiota transplantation (FMT). The composition of the gut microbiota in the cecum contents was analyzed by 16S rRNA sequencing, and the levels of BAs in liver and fecal samples were determined by UPLC/MS-MS.

RESULTS: The results showed that administration of PCPE for 8 weeks could potently ameliorate HFD-induced NAFLD and alleviate dyslipidemia and insulin resistance. Moreover, PCPE treatment alleviated gut dysbiosis, especially reducing the relative abundance of bile salt hydrolase (BSH)-producing bacteria. Furthermore, PCPE significantly increased the levels of taurine-conjugated BAs in feces, such as tauro-β-muricholic acid (T-βMCA), tauroursodesoxycholic acid (TUDCA), and taurochenodeoxycholic acid (TCDCA), and increased hepatic chenodeoxycholic acid (CDCA). The protein and mRNA expression of farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were decreased in intestine, increased taurine-conjugated BAs inhibited the intestinal signaling pathway, which was associated with increased genes expression of enzymes in the alternative BA synthesis pathway that reduced the levels of cholesterol. The increased CDCA produced via the alternative BA synthesis pathway promoted hepatic FXR activation and BA excretion.

CONCLUSION: Our study is the first time to demonstrate that PCPE could ameliorate NAFLD in HFD-induced mice by regulating the gut microbiota and BA metabolism, and from a novel view, to understand the mechanism of PCPE in NAFLD.

RevDate: 2022-05-02

Shen Q, Huang Z, Yao J, et al (2022)

Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease.

Journal of advanced research, 37:221-233 pii:S2090-1232(21)00136-3.

Background: The intestinal tract is a complicated ecosystem with dynamic homeostasis via interaction of intestine and microbiota. Inflammatory bowel disease (IBD) is chronic intestinal inflammation involving dysbiosis of intestinal microenvironment. Extracellular vesicles (EVs), as vital characteristics of cell-cell and cell-organism communication, contribute to homeostasis in intestine. Recently, EVs showed excellent potential for clinical applications in disease diagnoses and therapies.

Aim of Review: Our current review discusses the modulatory functions of EVs derived from different sources in intestine, especially their effects and applications in IBD clinical therapy. EV-mediated interaction systems between host intestine and microbiota were established to describe possible mechanisms of IBD pathogenesis and its cure.

EVs are excellent vehicles for delivering molecules containing genetic information to recipient cells. Multiple pieces of evidence have illustrated that EVs participate the interaction between host and microbiota in intestinal microenvironment. In inflammatory intestine with dysbiosis of microbiota, EVs as regulators target promoting immune response and microbial reconstruction. EVs-based immunotherapy could be a promising therapeutic approach for the treatment of IBD in the near future.

RevDate: 2022-05-02

Wu C, Zhao Y, Zhang Y, et al (2022)

Gut microbiota specifically mediates the anti-hypercholesterolemic effect of berberine (BBR) and facilitates to predict BBR's cholesterol-decreasing efficacy in patients.

Journal of advanced research, 37:197-208 pii:S2090-1232(21)00145-4.

Introduction: Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)'s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation.

Objectives: This study aims to confirm the causal role of the gut microbiota in BBR's anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness.

Methods: The correlation between gut microbiota and BBR's inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR's anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis.

Results: Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy.

Conclusion: The gut microbiota is necessary and sufficient for BBR's hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.

RevDate: 2022-05-02

Liu T, Guo Y, Lu C, et al (2022)

Effect of Different Pig Fecal Microbiota Transplantation on Mice Intestinal Function and Microbiota Changes During Cold Exposure.

Frontiers in veterinary science, 9:805815.

Cold stress influences intestinal processes, causing physiological and immunological responses in animals. Intestinal microbiota participates in maintaining the stability of the intestinal environment. However, phenotypic characteristics and the effects of porcine microbiota changes under cold conditions remain poorly understood. Here, the fecal microbiota of cold tolerant breed (Mashen) and cold sensitive breed (Duroc-Landrace-Yorkshire) was transferred to germ-free mice, respectively. After a cold exposure (4°C) for 21 days, intestinal function and microbe changes of mice were explored. The results showed that Mashen pigs microbiota transplantation made the body temperature of the mice stable, in which the fat weight and expression of uncoupling protein 1 (UCP1), carnitine palmitoyltransferase 1B (Cpt1b), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly higher (P < 0.05) than those of the control group. The results of intestinal structure and expression of serum inflammatory factors showed that fecal microbiota transplantation (FMT) mice have more intact intestinal structure and high expression of proinflammatory factor such as interleukin-4 (IL-4). The study of mice fecal microbiome characterized via 16S rRNA sequencing found that pig microbiota transplantation changed the abundance of Firmicutes. In addition, it identified discriminative features of Firmicutes in the microbiota between two breeds of pig, in which Clostridiaceae were enriched in the microbiota community of Mashen pig and Coriobacteriales were significantly (P < 0.05) enriched in the Duroc-Landrace-Yorkshire pig microbiota transplantation group based on linear discriminant analysis effect size (LEfSe) analysis. Finally, we found that the content of propionic acid and butyric acid in rectal contents significantly changed and the abundances of Clostridium and Lachnospira showed significant correlations with changes in short-chain fatty acids. The results suggest that pig fecal microbiota transplantation can alleviate the changes in physiological and biochemical indicators in mice caused by cold exposure. Mice have gut microbes altered and improved gut barrier function via fecal microbiota transplantation in pigs.

RevDate: 2022-05-02

Wang Q, Wang X, Lv Y, et al (2021)

Changes in Rats' Gut Microbiota Composition Caused by Induced Chronic Myocardial Infarction Lead to Depression-Like Behavior.

Frontiers in microbiology, 12:641084.

Depression is common among patients who have chronic myocardial infarction (CMI). Despite their frequency, depression and CMI are bidirectional related conditions, each is a risk for the other, and they often co-exist, suggesting shared or interacting pathomechanisms. Accumulating data revealed the effects of gut microbiota in terms of regulating depression via the gut-brain axis. Thus, we investigated the role of gut microbial dysbiosis in CMI-induced depression-like behavior. Hierarchical cluster analysis of sucrose preference test (SPT) results was adopted to classify the CMI rats into depression-like behavior (CMI + Dep) or non-depression-like behavior (CMI + Non-Dep) phenotypes. First, 16S ribosomal RNA sequencing analysis showed both β-diversity and relative abundance of several gut bacteria significantly differed between the CMI + Dep and CMI + Non-Dep rats. Next, transplantation of fecal microbiota from CMI + Dep rats visibly altered the relative abundance of gut microbiota and also induced depression-like behavior in the antibiotics-treated pseudo-germ-free rats. In conclusion, these findings suggested that dysbiosis in gut microbial composition contributed to the onset of CMI-induced depression-like behavior and that exogenous regulation of gut microbiota composition could be a potential therapeutic strategy for CMI and related depression-like behavior.

RevDate: 2022-05-02

Xu P, Lv T, Dong S, et al (2022)

Association between intestinal microbiome and inflammatory bowel disease: Insights from bibliometric analysis.

Computational and structural biotechnology journal, 20:1716-1725 pii:S2001-0370(22)00123-4.

The gut microbiome is highly linked to inflammatory bowel disease (IBD). A total of 3890 publications related to the two terms from 2000 to 2020 were extracted from the Web of Science Core Collection to study the association from a bibliometric perspective. Publications on this topic have grown rapidly since 2008. The United States and Harvard University are the country and institution with the largest number of publications, respectively. Inflammatory Bowel Diseases is the most productive journal with 211 published articles. The most influential journal in this field is Gut with 13,359 citations. The co-citation analysis of references showed that the IBD-related topics with the highest focus are "gut microbiota," "metagenomics," "bacterial community," "fecal microbiota transplantation," "probiotics," and "colitis-associated colorectal cancer." Keyword cluster and keyword burst analyses showed that "gut microbiota," "metagenomics," and "fecal microbiota transplantation" are currently the most researched topics in the field of IBD. The literature in this field is mainly distributed between alterations of the intestinal microbiota, microbial metabolites, and related host signaling pathways. Probiotic treatment also frequently appears in literature. This bibliometric analysis can guide future research and promote the development of the field of gut microbiome and IBD.

RevDate: 2022-03-08
CmpDate: 2022-03-08

Lai HC, Lin TL, Chen TW, et al (2022)

Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide.

Gut, 71(2):309-321.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.

DESIGN: A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.

RESULTS: Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.

CONCLUSION: The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

RevDate: 2022-04-30

Ezquer F, Quintanilla ME, Morales P, et al (2022)

A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player.

Drug and alcohol dependence, 236:109466 pii:S0376-8716(22)00203-4 [Epub ahead of print].

RATIONALE: Gut microbiota communicates information to the brain. Some animals are born with a gut microbiota that predisposes to high alcohol consumption, and transplantation of fecal material from alcoholics to mice increases animal preference for ethanol. Alcohol-use-disorders are chronic conditions where relapse is the hallmark. A predictive animal model of relapse is the "alcohol deprivation effect" where ethanol re-access is allowed following chronic alcohol intake and a long alcohol deprivation. The present study evaluates the effect of gut microbiota modification on relapse, as an adjunct to N-acetylcysteine + Acetylsalicylic acid administration, which inhibits the alcohol-induced hyper-glutamatergic condition.

METHODS: Rats bred as heavy alcohol consumers (UChB) were allowed ethanol intake for one month, were deprived of alcohol for two-weeks and subsequently offered re-access to ethanol. Prior to ethanol re-access animals received orally either (i) vehicle-control, (ii) Lactobacillus-rhamnosus-GG after antibiotic treatment (LGG); (iii) N-acetylcysteine+Acetylsalicylic acid (NAC/ASA) or (iv) both treatments: LGG+ (NAC/ASA).

RESULTS: Marked binge drinking (1.75 g ethanol/kg in 60 min) and blood alcohol levels exceeding 80 mg/dl were observed in the control group upon ethanol-re-access. Lactobacillus-GG or (NAC+ASA) treatments inhibited alcohol intake by 66-80%. The combination of both treatments virtually suppressed (inhibition of 90%) the re-access binge-like drinking, showing additive effects. Treatment with NAC+ASA increased the levels of glutamate transporters xCT and GLT-1 in nucleus accumbens, while Lactobacillus-GG administration increased those of the dopamine transporter (DAT).

CONCLUSIONS: The administration of a well-accepted probiotic may be of value as an adjunct in the treatment of alcohol-use-disorders.

RevDate: 2022-04-29

Lu Y, Yuan X, Wang M, et al (2022)

Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies.

Journal of hematology & oncology, 15(1):47.

The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.

RevDate: 2022-04-29

Wang B, Zhang L, Wang Y, et al (2022)

Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions.

Signal transduction and targeted therapy, 7(1):143.

The global coronavirus disease 2019 (COVID-19) pandemic is currently ongoing. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high proportion of COVID-19 patients exhibit gastrointestinal manifestations such as diarrhea, nausea, or vomiting. Moreover, the respiratory and gastrointestinal tracts are the primary habitats of human microbiota and targets for SARS-CoV-2 infection as they express angiotensin-converting enzyme-2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) at high levels. There is accumulating evidence that the microbiota are significantly altered in patients with COVID-19 and post-acute COVID-19 syndrome (PACS). Microbiota are powerful immunomodulatory factors in various human diseases, such as diabetes, obesity, cancers, ulcerative colitis, Crohn's disease, and certain viral infections. In the present review, we explore the associations between host microbiota and COVID-19 in terms of their clinical relevance. Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.

RevDate: 2022-04-29

El-Salhy M, Mazzawi T, Hausken T, et al (2022)

The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms.

Scandinavian journal of gastroenterology [Epub ahead of print].

OBJECTIVES: Fecal microbiota transplantation (FMT) is a promising intervention for patients with irritable bowel syndrome (IBS). The present study aimed to identify any differences in FMT response between patients with severe and moderate IBS symptoms.

MATERIALS AND METHOD: The study included the 164 patients who participated in our previous study, of which 96 (58.5%) and 68 (41.5%) had severe (S-IBS-S) and moderate (Mo-IBS-S) IBS, respectively. The patients were randomly divided into a placebo group (own feces) and 30-g and 60-g (donor feces) FMT groups. Patients completed three questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT, and provided fecal samples before and 1 month after FMT. The fecal bacteria were analyzed using the 16S rRNA gene in PCR DNA amplification covering the V3-V9 variable genes.

RESULTS: Response rates of the placebo group did not differ between S-IBS-S and Mo-IBS-S patients at 2 weeks, 1 month and 3 months after FMT. The response rates in the active treatment group were higher in S-IBS-S patients than in Mo-IBS-S patients at each observation time. FMT reduced abdominal symptoms and fatigue and improved the quality of life in patients with both severe and moderate IBS. Patients with S-IBS-S had higher levels of Eubacterium siraeum, and lower levels of Eubacterium rectale than Mo-IBS-S, after FMT.

CONCLUSION: Patients with S-IBS-S have a higher response rate to FMT and a marked improvement in fatigue and in quality of life compared with those with Mo-IBS-S. The clinical trial registration number is NCT03822299 and is available at www.clinicaltrials.gov.

RevDate: 2022-04-28

Zou YT, Zhou J, Zhu JH, et al (2022)

Gut Microbiota Mediates the Protective Effects of Traditional Chinese Medicine Formula Qiong-Yu-Gao against Cisplatin-Induced Acute Kidney Injury.

Microbiology spectrum [Epub ahead of print].

Our previous study found that Qiong-Yu-Gao (QYG), a traditional Chinese medicine formula derived from Rehmanniae Radix, Poria, and Ginseng Radix, has protective effects against cisplatin-induced acute kidney injury (AKI), but the underlying mechanisms remain unknown. In the present study, the potential role of gut microbiota in the nephroprotective effects of QYG was investigated. We found that QYG treatment significantly attenuated cisplatin-induced AKI and gut dysbiosis, altered the levels of bacterial metabolites, with short-chain fatty acids (SCFAs) such as acetic acid and butyric acid increasing and uremic toxins such as indoxyl sulfate and p-cresyl sulfate reducing, and suppressed histone deacetylase expression and activity. Spearman's correlation analysis found that QYG-enriched fecal bacterial genera Akkermansia, Faecalibaculum, Bifidobacterium, and Lachnospiraceae_NK4A136_group were correlated with the altered metabolites, and these metabolites were also correlated with the biomarkers of AKI, as well as the indicators of fibrosis and inflammation. The essential role of gut microbiota was further verified by both the diminished protective effects with antibiotics-induced gut microbiota depletion and the transferable renal protection with fecal microbiota transplantation. All these results suggested that gut microbiota mediates the nephroprotective effects of QYG against cisplatin-induced AKI, potentially via increasing the production of SCFAs, thus suppressing histone deacetylase expression and activity, and reducing the accumulation of uremic toxins, thereby alleviating fibrosis, inflammation, and apoptosis in renal tissue. IMPORTANCE Cisplatin-induced acute kidney injury is the main limiting factor restricting cisplatin's clinical application. Accumulating evidence indicated the important role of gut microbiota in pathogenesis of acute kidney injury. In the present study, we have demonstrated that gut microbiota mediates the protective effects of traditional Chinese medicine formula Qiong-Yu-Gao against cisplatin-induced acute kidney injury. The outputs of this study would provide scientific basis for future clinical applications of QYG as prebiotics to treat cisplatin-induced acute kidney injury, and gut microbiota may be a promising therapeutic target for chemotherapy-induced nephrotoxicity.

RevDate: 2022-04-28

Hu B, Das P, Lv X, et al (2022)

Effects of 'Healthy' Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats.

mSystems [Epub ahead of print].

Depression is a recurrent, heterogeneous mood disorder occurring in more than 260 million people worldwide. Gut microbiome dysbiosis is associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through the microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression, but the therapeutic efficiency and mechanism are unknown. Here, we performed an FMT from Sprague-Dawley (SD) rats ('healthy' controls) to Fawn-hooded (FH) rats (depression model). Pre-FMT, the FH rats exhibited significantly elevated depressive-like behaviors and distinct neurotransmitter and cytokine levels compared with SD rats. Post-FMT, FH recipients receiving FH fecal microbiota (FH-FH rats) showed aggravated depressive-like behaviors, while the ones receiving SD microbiota (FH-SD rats) had significantly alleviated depressive symptoms, a significant increase in hippocampal neurotransmitters, and a significant decrease of some hippocampal cytokines than FH-FH rats. SD-FMT resulted in the FH-SD rats' gut microbiome resembling the SD donors, and a significant shift in the serum metabolome but not the hippocampal metabolome. Co-occurrence analysis suggests that SD-FMT prevented recipients' depression development via the significant decrease of gut microbial species such as Dialister sp., which led to the recipients' metabolic modulation in serum and hippocampus through the enteric nervous system, the intestinal barrier, and the blood-brain barrier. Our results provided new data pointing to multiple mechanisms of interaction for the impact of gut microbiome modulation on depression therapy. IMPORTANCE Depression is a chronic, recurrent mental disease, which could make the patients commit suicide in severe cases. Considering that gut microbiome dysbiosis could cause depressive symptoms in animals through the MGB axis, the modification of gut microbiota is expected to be a potential therapy for depression, but the daily administration of probiotics is invalid or transient. In this study, we demonstrated that the gut microbiome transferred from a healthy rat model to a depressive rat model could regulate the recipient's neurobiology and behavior via the systematic alternation of the depressive gut microbiota followed by the serum and hippocampal metabolism. These results underline the significance of understanding the impact of gut microbiota on mental disorders and suggest that 'healthy' microbiota transplantation with the function to solve the host's cerebral inflammation may serve as a novel therapeutic strategy for depression.

RevDate: 2022-04-28

Rapoport EA, Baig M, SR Puli (2022)

Adverse events in fecal microbiota transplantation: a systematic review and meta-analysis.

Annals of gastroenterology, 35(2):150-163.

Background: Fecal microbiota transplantation (FMT) is a highly efficacious procedure used most commonly for the treatment of recurrent Clostridioides difficile infection (CDI). Despite the high value of incorporating FMT into practice, there remain concerns about its safety. To the best of our knowledge, there has not been an updated meta-analysis reporting pooled rates of adverse events in FMT for CDI.

Methods: A search for studies of FMT in patients with CDI was performed with the rate of serious adverse events (SAEs) related to FMT evaluated as the primary outcome. Secondary outcomes included SAEs unrelated to FMT and minor adverse events associated with FMT. A pooled analysis was then performed.

Results: Initial search identified 378 reference articles. Data were extracted from the 61 of these studies that met the inclusion criteria, comprising 5099 patients. Pooled analysis showed that SAEs related to FMT developed in less than 1% of patients. The pooled rate of SAEs not related to FMT was higher at 2.9%. The pooled rate of minor adverse events also showed infrequent self-limited gastrointestinal and systemic discomfort.

Conclusions: This meta-analysis supports FMT as a safe option for treating recurrent CDI. Future randomized trials are needed to improve our current understanding of FMT safety and further examine the improvements in the quality of life of patients treated with FMT compared to standard therapy of antibiotics.

RevDate: 2022-04-28
CmpDate: 2022-04-28

Fobofou SA, T Savidge (2022)

Microbial metabolites: cause or consequence in gastrointestinal disease?.

American journal of physiology. Gastrointestinal and liver physiology, 322(6):G535-G552.

Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancer, metabolic disorders, and opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiological host-microbiome interactions. Generally, to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles, and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short-chain fatty acids, polysaccharides, and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthesized by microbial biosynthetic gene clusters, including ribosomally synthesized and posttranslationally modified peptides (RiPPs), nonribosomal peptides (NRPs), polyketides (PKs), PK-NRP hybrids, and terpenes. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.

RevDate: 2022-04-27

Li S, Zhao X, Lin F, et al (2022)

Gut Flora Mediates the Rapid Tolerance of Electroacupuncture on Ischemic Stroke by Activating Melatonin Receptor through Regulating Indole-3-Propionic Acid.

The American journal of Chinese medicine [Epub ahead of print].

Electroacupuncture (EA) is commonly used to treat cerebrovascular diseases. This study aimed to clarify the mechanisms of action of treatments of cerebral ischemic stroke from the perspective of gut microecology. We used a mouse model and cell cultures to investigate the effects of EA on the intestinal microflora in mice models of middle cerebral artery occlusion (MCAO) and the mechanisms underlying the antioxidant activities of metabolites. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota. Metabolomic analysis was performed to characterize the metabolic profile differences between the mice in the EA + MCAO and MCAO groups. Gavaging with feces relieved brain damage in mice that received EA (EA mice) more than in mice that did not (non-EA [NEA] mice). The gut microbial composition and metabolic profiles of the EA and NEA mice were different. In particular, the microbiota from the mice in the EA or EA-FMT groups generated more indole-3-propionic acid (IPA) than the microbiota from the mice in the MCAO or NEA-FMT groups. We confirmed that IPA binds to specific melatonin receptors (MTRs) in target cells and exerts antioxidant effects by adding MTR inhibitors or knocking out the MTR1 gene in vivo and in the oxygen and glucose deprivation/reperfusion models of N2a cell experiments. EA can prevent ischemic stroke by improving the composition of intestinal microbiota in MCAO mice. Moreover, this study reveals a new mechanism of intestinal flora regulation of stroke that differs from inflammation/immunity, namely gut microbiota regulates stroke by affecting IPA levels.

RevDate: 2022-04-27

Kumar P, Brazel D, DeRogatis J, et al (2022)

The cure from within? a review of the microbiome and diet in melanoma.

Cancer metastasis reviews [Epub ahead of print].

Therapy for cutaneous melanoma, the deadliest of the skin cancers, is inextricably linked to the immune system. Once thought impossible, cures for metastatic melanoma with immune checkpoint inhibitors have been developed within the last decade and now occur regularly in the clinic. Unfortunately, half of tumors do not respond to checkpoint inhibitors and efforts to further exploit the immune system are needed. Tantalizing associations with immune health and gut microbiome composition suggest we can improve the success rate of immunotherapy. The gut contains over half of the immune cells in our bodies and increasingly, evidence is linking the immune system within our gut to melanoma development and treatment. In this review, we discuss the importance the skin and gut microbiome may play in the development of melanoma. We examine the differences in the microbial populations which inhabit the gut of those who develop melanoma and subsequently respond to immunotherapeutics. We discuss the role of dietary intake on the development and treatment of melanoma. And finally, we review the landscape of published and registered clinical trials therapeutically targeting the microbiome in melanoma through dietary supplements, fecal microbiota transplant, and microbial supplementation.

RevDate: 2022-04-26

Zhu L, Ye C, Hu B, et al (2022)

Regulation of gut microbiota and intestinal metabolites by Poria cocos oligosaccharides improves glycolipid metabolism disturbance in high-fat diet-fed mice.

The Journal of nutritional biochemistry pii:S0955-2863(22)00090-0 [Epub ahead of print].

In this study, we aimed to explore the effect of Poria cocos oligosaccharides (PCO) on glucolipid metabolism disorder. Based on a high-fat diet (HFD)-induced obese mouse model, we demonstrated that PCO ameliorated glucose intolerance and insulin resistance, decreased the levels of blood glucose (187.8 ± 19.8 mg/dL) and insulin (566.3 ± 53.34 ng/L) in HFD-fed mice compared to the Ctrl group (140.4 ± 7.942 mg/dL for glucose, 423.2 ± 19.56 ng/L for insulin). Moreover, PCO treatment suppressed the mRNA expressions of fatty acid synthesis regulators (decreases of 68.8%, 62.8%, and 32.0% for G6Pase, FASN, and DGAT, respectively, vs HFD group) and pro-inflammatory cytokines in epididymal fat (decreases of 71.9%, 81.5%, 76.0%, 29.3%, and 63.9% for TNF-α, IL-1β, IL-6, COX-5b, and MCP-1, respectively, vs HFD group). Also, PCO treatment alleviated damage to the intestinal barrier of HFD-fed mice. By 16S rDNA gene sequencing, PCO partly restored the imbalance of gut microbiota in HFD-fed mice, accompanied by the reversal of several intestinal metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and tryptophan metabolites. By Spearman's correlation analysis, we found that the changed gut microbiota and their metabolites were significantly correlated with the alteration of metabolic markers. Finally, the significance of gut microbiota in PCO-mediated improvement on glucolipid metabolism disorder was confirmed by an antibiotic depletion experiment and fecal microbiota transplantation. In summary, PCO may be used as a novel prebiotic in the treatment of glucolipid disorders by reshaping intestinal bacteria structure. Our studies also point towards the potential of Poria cocos as a healthy food in the clinical application to metabolic diseases in the future.

RevDate: 2022-04-26

Hao Y, Feng Y, Yan X, et al (2022)

Gut microbiota-testis axis: FMT improves systemic and testicular micro-environment to increase semen quality in type 1 diabetes.

Molecular medicine (Cambridge, Mass.), 28(1):45.

BACKGROUND: Clinical data suggest that male reproductive dysfunction especially infertility is a critical issue for type 1 diabetic patient (T1D) because most of them are at the reproductive age. Gut dysbiosis is involved in T1D related male infertility. However, the improved gut microbiota can be used to boost spermatogenesis and male fertility in T1D remains incompletely understood.

METHODS: T1D was established in ICR (CD1) mice with streptozotocin. Alginate oligosaccharide (AOS) improved gut microbiota (fecal microbiota transplantation (FMT) from AOS improved gut microbiota; A10-FMT) was transplanted into the T1D mice by oral administration. Semen quality, gut microbiota, blood metabolism, liver, and spleen tissues were determined to investigate the beneficial effects of A10-FMT on spermatogenesis and underlying mechanisms.

RESULTS: We found that A10-FMT significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver functions to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent.

CONCLUSIONS: AOS-improved gut microbiota (specific microbes) may serve as a novel, promising therapeutic approach for the improvement of semen quality and male fertility in T1D patients via gut microbiota-testis axis.

RevDate: 2022-04-25

Xiao Y, Zhong XS, Liu X, et al (2022)

Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-deficient Mouse Model.

Journal of visualized experiments : JoVE.

With the development of microecology in recent years, the relationship between intestinal bacteria and inflammatory bowel disease (IBD) has attracted considerable attention. Accumulating evidence suggests that dysbiotic microbiota plays an active role in triggering or worsening the inflammatory process in IBD and that fecal microbiota transplantation (FMT) is an attractive therapeutic strategy since transferring a healthy microbiota to IBD patient could restore the appropriate host-microbiota communication. However, the molecular mechanisms are unclear, and the efficacy of FMT has not been very well established. Thus, further studies in animal models of IBD are necessary. In this method, we applied FMT from wild-type C57BL/6J mice to IL-10 deficient mice, a widely used mouse model of colitis. The study elaborates on collecting fecal pellets from the donor mice, making the fecal solution/suspension, administering the fecal solution, and monitoring the disease. We found that FMT significantly mitigated the cardiac impairment in IL-10 knockout mice, underlining its therapeutic potential for IBD management.

RevDate: 2022-04-25

Jing Y, Bai F, Wang L, et al (2022)

Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site.

Microbiology spectrum [Epub ahead of print].

The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and β-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with β-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that β-alanine might be one of the mediators following FMT that has contributed to the recovery.

RevDate: 2022-04-25

Feng T, Y Liu (2022)

Microorganisms in the reproductive system and probiotic's regulatory effects on reproductive health.

Computational and structural biotechnology journal, 20:1541-1553 pii:S2001-0370(22)00092-7.

The presence of microbial communities in the reproductive tract has been revealed, and this resident microbiota is involved in the maintenance of health. Intentional modulation via probiotics has been proposed as a possible strategy to enhance reproductive health and reduce the risk of diseases. The male seminal microbiota has been suggested as an important factor that influences a couple's health, pregnancy outcomes, and offspring health. Probiotics have been reported to play a role in male fertility and to affect the health of mothers and offspring. While the female reproductive microbiota is more complicated and has been identified in both the upper and lower reproductive systems, they together contribute to health maintenance. Probiotics have shown regulatory effects on the female reproductive tract, thereby contributing to homeostasis of the tract and influencing the health of offspring. Further, through transmission of bacteria or through other indirect mechanisms, the parent's reproductive microbiota and probiotic intervention influence infant gut colonization and immunity development, with potential health consequences. In vitro and in vivo studies have explored the mechanisms underlying the benefits of probiotic administration and intervention, and an array of positive results, such as modulation of microbiota composition, regulation of metabolism, promotion of the epithelial barrier, and improvement of immune function, have been observed. Herein, we review the state of the art in reproductive system microbiota and its role in health and reproduction, as well as the beneficial effects of probiotics on reproductive health and their contributions to the prevention of associated diseases.

RevDate: 2022-04-25

Hammeken LH, Baunwall SMD, Dahlerup JF, et al (2022)

Health-related quality of life in patients with recurrent Clostridioides difficile infections.

Therapeutic advances in gastroenterology, 15:17562848221078441 pii:10.1177_17562848221078441.

Background: The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI.

Methods: Patients' HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n = 16), fidaxomicin (n = 24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n = 24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients' HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p < 0.05).

Results: Within 26 weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p < 0.001) at week 8 and by 0.098 to 0.773 (p = 0.003) at week 26 of follow-up compared with baseline.

Conclusion: The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure.

Trial registration: The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234).

RevDate: 2022-04-24

Zhou Y, Li YY, Y Liu (2022)

[Effect of fecal microbiota transplantation on type 1 diabetes mellitus in non-obese diabetic mice and its underlying mechanism].

Zhonghua yi xue za zhi, 102(16):1224-1231.

Objective: To investigate the effects of fecal microbiota transplantation (FMT) on non-obese diabetic (NOD) mice of type 1 diabetes mellitus (T1DM) and its underlying mechanisms. Methods: A total of 8-9 week-female NOD mice were randomly divided into control (n=36) and FMT groups (n=36) according to the random number table. Fecal microbiota from C57BL/6 mice were transplanted into FMT group, and control group were transplanted with microbiota from themselves, once every two days for 5 times. The insulitis score and incidence of T1DM were compared between two groups;16S rRNA gene sequencing was used to evaluate the structure of fecal bacteria in NOD mice. The expressions of intestinal barrier related genes were detected by real-time quantitative PCR. The proportions of regulatory T cells (Tregs), helper T cell (Th)-1 and Th17 in the enteric-pancreatic immune axis were detected by flow cytometry. Amino acid in serum was measured by amino acid metabolomics. Results: Incidence of T1DM in NOD mice from FMT group was 40.9% (9/22), lower than 72.7% (13/22) from control group at 26 weeks of age (P=0.034). FMT promoted colonization of probiotics such as Lactobacillus, Clostridium_sp_ND2, Candidatus_Arthromitus and Clostridiaceae_1; mRNA of intestinal barrier related genes were up-regulated in FMT group [ mucins(Muc)-1: 0.93±0.29 vs 2.97±0.79, P=0.036; Muc2: 0.72±0.39 vs 10.70±3.54, P=0.019;Muc3: 1.79±0.69 vs 10.97±2.78, P=0.009;Muc4: 1.01±0.23 vs 2.42±0.49, P=0.029;Occludin(Ocln): 0.96±0.08 vs 1.81±0.36, P=0.045; Claudin(Cldn)-1:0.94±0.17 vs 2.20±0.43, P=0.022] compared to control. The proportions of Treg in mesenteric lymphoid node, pancreatic lymph node and peyer's patches of FMT group [(6.10±0.49)% vs (7.54±0.27)%, P=0.020;(5.28±0.39)% vs (6.42±0.34)%, P=0.048;(6.78±0.42)% vs (7.88±0.13)%, P=0.029] were increased compared to control,while proportions of Th1 [(1.02±0.06)% vs (0.83±0.06)%, P=0.040;(0.82±0.10)% vs (0.56±0.05)%, P=0.038;(1.28±0.12) vs (0.85±0.07), P=0.012] and proportions of Th17 [(0.40±0.01)% vs (0.30±0.02)%, P=0.004;(0.40±0.02)% vs (0.31±0.02)%, P=0.008;(0.51±0.06) vs (0.36±0.02), P=0.027] were decreased. The contents of leucine [(92.86±7.32) vs (91.87±12.62) μmol/L, P=0.027], valine [(162.74±15.97) vs (155.89±25.70) μmol/L, P=0.046] and isoleucine [(75.65±5.59) vs (73.61±9.67) μmol/L, P=0.048] in serum were decreased in FMT group. Conclusions: FMT can alleviate insulitis and T1DM occurrence in NOD mice, of which mechanism may be related to remodeling gut microbiota and improving intestinal barrier function, affecting immune response of enteric-pancreatic immune axis, correcting amino acid metabolism disorder and reducing the accumulation of branch chain amino acids in NOD mice.

RevDate: 2022-04-24

Macareño-Castro J, Solano-Salazar A, Dong LT, et al (2022)

Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review.

The Journal of infection pii:S0163-4453(22)00207-9 [Epub ahead of print].

The prevalence of Carbapenem-resistant Enterobacteriaceae (CRE) has increased dramatically in recent years and has become a global public health issue. Since carbapenems are considered the last drugs of choice, infections caused by these pathogens are difficult to treat and carry a high risk of mortality. Several antibiotic combination regimens have been utilized for the management of CRE infections or to eradicate colonization in CRE carriers with variable clinical responses. In addition, recent studies have explored the use of fecal microbiota transplantation (FMT) to eradicate CRE infections. Here, we conducted a systematic review of publications in which FMT was used to eliminate CRE colonization in infected individuals. We searched the PubMed, Cochrane, and Medline databases up to November 30, 2021. Ten studies (209 patients) met the inclusion criteria for this review with three articles describing retrospective cohorts (n = 53 patients) and seven reporting prospective data (n = 156 patients), including one randomized open-label clinical trial. All studies were published between 2017 and 2021 with eight studies from Europe and two from South Korea. There were substantial variations in terms of outcome measurements and study endpoint among these studies. Among the 112 FMT recipients with confirmed CRE colonization, CRE decolonization was reported in 55/90 cases at one month after FMT and at the end of the study follow-up (6-12 months), decolonization was documented in 74/94 (78.7%) patients. The predominant CRE strains reported were Klebsiella pneumoniae and Escherichia coli and the most frequently documented carbapenemases were KPC, OXA-48, and NDM. In general, FMT was well tolerated, with no severe complications reported even in immunosuppressed patients and in those with multiple underlying conditions. In conclusion, FMT appears to be safe and effective in eradicating CRE colonization, however, more studies, especially randomized trials, are needed to validate the safety and clinical utility of FMT for CRE eradication.

RevDate: 2022-04-24

Hou K, Wu ZX, Chen XY, et al (2022)

Microbiota in health and diseases.

Signal transduction and targeted therapy, 7(1):135.

The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.

RevDate: 2022-04-23

Thye AY, Law JW, Tan LT, et al (2022)

Exploring the Gut Microbiome in Myasthenia Gravis.

Nutrients, 14(8): pii:nu14081647.

The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host's antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota's relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG's clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.

RevDate: 2022-04-23

Liu X, Hu G, Wang A, et al (2022)

Black Tea Reduces Diet-Induced Obesity in Mice via Modulation of Gut Microbiota and Gene Expression in Host Tissues.

Nutrients, 14(8): pii:nu14081635.

Black tea was reported to alter the microbiome populations and metabolites in diet-induced obese mice and displays properties that prevent obesity, but the underlying mechanism of the preventative effect of black tea on high-fat diet (HFD) induced obesity has not been elucidated. Epigenetic studies are a useful tool for determining the relationship between obesity and environment. Here, we show that the water extract of black tea (Lapsang souchong, LS) reverses HFD-induced gut dysbiosis, alters the tissue gene expression, changes the level of a major epigenetic modification (DNA methylation), and prevents obesity in HFD feeding mice. The anti-obesity properties of black tea are due to alkaloids, which are the principal active components. Our data indicate that the anti-obesity benefits of black tea are transmitted via fecal transplantation, and the change of tissue gene expression and the preventative effects on HFD-induced obesity in mice of black tea are dependent on the gut microbiota. We further show that black tea could regulate the DNA methylation of imprinted genes in the spermatozoa of high-fat diet mice. Our results show a mechanistic link between black tea, changes in the gut microbiota, epigenetic processes, and tissue gene expression in the modulation of diet-induced metabolic dysfunction.

RevDate: 2022-04-23

van Thiel IAM, Rahman S, Hakvoort TBM, et al (2022)

Fecal Filobasidium Is Associated with Clinical Remission and Endoscopic Response following Fecal Microbiota Transplantation in Mild-to-Moderate Ulcerative Colitis.

Microorganisms, 10(4): pii:microorganisms10040737.

Fecal microbiota transplantation (FMT) has the potential to restore (bacterial and fungal) microbial imbalance in ulcerative colitis (UC) patients and contribute to disease remission. Here, we aimed to identify fecal fungal species associated with the induction of clinical remission and endoscopic response to FMT for patients with mild-to-moderate ulcerative colitis. We analyzed the internal transcribed spacer 1 (ITS1)-based mycobiota composition in fecal samples from patients (n = 31) and donors (n = 7) that participated previously in a double-blinded randomized control trial evaluating the efficacy of two infusions of donor FMT compared with autologous FMT. The abundance of the yeast genus Filobasidium in fecal material used for transplantation was shown to correlate with clinical remission following FMT, irrespective of its presence in the material of donor or autologous fecal microbiota transfer. The amplified sequence variants within the genus Filobasidium most closely resembled Filobasidium magnum. Monocyte-derived macrophages and HT29 epithelial cells were stimulated with fungal species. Especially Filobasidium floriforme elicited an IL10 response in monocyte-derived macrophages, along with secretion of other cytokines following stimulation with other Filobasidium species. No effect of Filobasidium spp. was seen on epithelial wound healing in scratch assays. In conclusion, the enriched presence of Filobasidium spp. in donor feces is associated with the positive response to FMT for patients with UC and hence it may serve as a predictive fungal biomarker for successful FMT.

RevDate: 2022-04-23

Monteiro RC, Rafeh D, PJ Gleeson (2022)

Is There a Role for Gut Microbiome Dysbiosis in IgA Nephropathy?.

Microorganisms, 10(4): pii:microorganisms10040683.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and one of the leading causes of renal failure worldwide. The pathophysiology of IgAN involves nephrotoxic IgA1-immune complexes. These complexes are formed by galactose-deficient (Gd) IgA1 with autoantibodies against the hinge region of Gd-IgA1 as well as soluble CD89, an immune complex amplifier with an affinity for mesangial cells. These multiple molecular interactions result in the induction of the mesangial IgA receptor, CD71, injuring the kidney and causing disease. This review features recent immunological and microbiome studies that bring new microbiota-dependent mechanisms developing the disease based on data from IgAN patients and a humanized mouse model of IgAN. Dysbiosis of the microbiota in IgAN patients is also discussed in detail. Highlights of this review underscore that nephrotoxic IgA1 in the humanized mice originates from mucosal surfaces. Fecal microbiota transplantation (FMT) experiments in mice using stools from patients reveal a possible microbiota dysbiosis in IgAN with the capacity to induce progression of the disease whereas FMT from healthy hosts has beneficial effects in mice. The continual growth of knowledge in IgAN patients and models can lead to the development of new therapeutic strategies targeting the microbiota to treat this disease.

RevDate: 2022-04-23

Sonali S, Ray B, Ahmed Tousif H, et al (2022)

Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review.

Cells, 11(8): pii:cells11081362.

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus-pituitary-adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut-brain axis (GBA) for the effective management of depressive behavior and anxiety.

RevDate: 2022-04-23

Di Domenico M, Ballini A, Boccellino M, et al (2022)

The Intestinal Microbiota May Be a Potential Theranostic Tool for Personalized Medicine.

Journal of personalized medicine, 12(4): pii:jpm12040523.

The human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized "mold" for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy.

RevDate: 2022-04-23

Lian WS, Wang FS, Chen YS, et al (2022)

Gut Microbiota Ecosystem Governance of Host Inflammation, Mitochondrial Respiration and Skeletal Homeostasis.

Biomedicines, 10(4): pii:biomedicines10040860.

Osteoporosis and osteoarthritis account for the leading causes of musculoskeletal dysfunction in older adults. Senescent chondrocyte overburden, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability are prominent features of these age-mediated skeletal diseases. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Dysregulation of gut microflora correlates with development of osteoarthritis and osteoporosis in humans and rodents. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes and bone cells to regulate joint and bone tissue homeostasis. Modulating the abundance of Lactobacillus and Bifidobacterium, or the ratio of Firmicutes and Bacteroidetes, in the gut microenvironment by probiotics or fecal microbiota transplantation is advantageous to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue. Supplementation with gut microbiota-derived metabolites potentially slows down development of osteoarthritis and osteoporosis. This review provides latest molecular and cellular insights into the biological significance of gut microorganisms and primary and secondary metabolites important to cartilage and bone integrity. It further highlights treatment options with probiotics or metabolites for modulating the progression of these two common skeletal disorders.

RevDate: 2022-04-23

Biliński J, Jasiński M, GW Basak (2022)

The Role of Fecal Microbiota Transplantation in the Treatment of Acute Graft-versus-Host Disease.

Biomedicines, 10(4): pii:biomedicines10040837.

The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but only 40-60% of patients will respond to the therapy and some others will be steroid-dependent. There is still no consensus regarding the best second-line option, but fecal microbiota transplantation (FMT) has shown encouraging preliminary and first clinically relevant results in recent years and seems to offer great hope for patients. The reason for treatment of steroid-resistant acute GvHD using this method derives from studies showing the significant immunomodulatory role played by the intestinal microbiota in the pathogenesis of GvHD. Depletion of commensal microbes is accountable for aggravation of the disease and is associated with decreased overall survival. In this review, we present the pathogenesis of GvHD, with special focus on the special role of the gut microbiota and its crosstalk with immune cells. Moreover, we show the results of studies and case reports to date regarding the use of FMT in the treatment of steroid-resistant acute GvHD.

RevDate: 2022-04-22

Caira-Chuquineyra B, Fernandez-Guzman D, Soriano-Moreno DR, et al (2022)

Fecal microbiota transplantation for people living with HIV: A scoping review.

AIDS research and human retroviruses [Epub ahead of print].

The aim of the present scoping review was to determine the characteristics of studies evaluating fecal microbiota transplantation (FMT), as well as its effects and safety as a therapeutic intervention for people living with HIV. We conducted a scoping review following the methodology of the Joanna Briggs Institute. We searched the following databases: PubMed, Web of Science, Scopus, Embase, Cochrane Library, and Medline until September 19, 2021. Studies that used FMT in people living with HIV and explored its effects on the health of these people were included. Two randomized and two uncontrolled clinical trials with a total of 55 participants were included. Participants were well-controlled HIV infected people. Regarding microbiota changes, three studies found significant post-FMT increases in Fusobacterium, Prevotella, α-diversity, Chao-index, and/or Shannon-index, and/or decreases in Bacteroides. Regarding markers of intestinal damage, one study found a decrease in intestinal fatty-acid binding protein post- FMT, and another study found an increase in zonulin. Other outcomes evaluated by the studies were: markers of immune and inflammatory activation, markers of immunocompetence (CD4+, and CD8+ T lymphocytes), and HIV viral load; however, none showed significant changes. Clinical outcomes were not evaluated by these studies. Regarding the safety of FMT, only mild adverse events were appreciated. No serious adverse events were reported. The clinical evidence for FMT in people living with HIV is sparse. FMT appears to have good tolerability and, no serious adverse events have been reported so far. Further clinical trials and evaluation of clinically important biomedical outcomes for FMT in people living with HIV are needed.

RevDate: 2022-04-22

Wang Y, H Li (2022)

Gut microbiota modulation: a tool for the management of colorectal cancer.

Journal of translational medicine, 20(1):178.

Colorectal cancer (CRC) is the second cause of cancer death and the third most frequently diagnosed cancer. Besides the lifestyle, genetic and epigenetic alterations, and environmental factors, gut microbiota also plays a vital role in CRC development. The interruption of the commensal relationship between gut microbiota and the host could lead to an imbalance in the bacteria population, in which the pathogenic bacteria become the predominant population in the gut. Different therapeutic strategies have been developed to modify the gut immune system, prevent pathogen colonization, and alter the activity and composition of gut microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). Even though the employed strategies exhibit promising results, their translation into the clinic requires evaluating potential implications and risks, as well as assessment of their long-term effects. This study was set to review the gut microbiota imbalances and their relationship with CRC and their effects on CRC therapy, including chemotherapy and immunotherapy. More importantly, we reviewed the strategies that have been used to modulate gut microbiota, their impact on the treatment of CRC, and the challenges of each strategy.

RevDate: 2022-04-21

Anonymous (2022)

Eshel A, Sharon I, Nagler A, et al. Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis. Blood Adv. 2022;6(2):568-573.

Blood advances, 6(8):2578-2580.

RevDate: 2022-04-21

Hao Y, Feng Y, Yan X, et al (2022)

Gut Microbiota-Testis Axis: FMT Mitigates High-Fat Diet-Diminished Male Fertility via Improving Systemic and Testicular Metabolome.

Microbiology spectrum [Epub ahead of print].

High-fat diet (HFD)-induced obesity is known to be associated with reduced male fertility and decreased semen quality in humans. HFD-related male infertility is a growing issue worldwide, and it is crucial to overcome this problem to ameliorate the distress of infertile couples. For the first time, we discovered that fecal microbiota transplantation (FMT) of alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) ameliorated HFD-decreased semen quality (sperm concentration: 286.1 ± 14.1 versus 217.9 ± 17.4 million/mL; sperm motility: 40.1 ± 0.7% versus 29.0 ± 0.9%), and male fertility (pregnancy rate: 87.4 ± 1.1% versus 70.2 ± 6.1%) by benefiting blood and testicular metabolome. A10-FMT improved HFD-disturbed gut microbiota by increasing gut Bacteroides (colon: 24.9 ± 1.1% versus 8.3 ± 0.6%; cecum: 10.2 ± 0.7% versus 3.6 ± 0.7%) and decreasing Mucispirillum (colon: 0.3 ± 0.1% versus 2.8 ± 0.4%; cecum: 2.3 ± 0.5% versus 6.6 ± 0.7%). A10-FMT benefited gut microbiota to improve liver function by adjusting lipid metabolism to produce n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (blood: 55.5 ± 18.7 versus 20.3 ± 2.4) and docosahexaenoic acid (testis: 121.2 ± 6.2 versus 89.4 ± 6.7), thus ameliorating HFD-impaired testicular microenvironment to rescue spermatogenesis and increase semen quality and fertility. The findings indicated that AOS-improved gut microbiota may be a promising strategy to treat obesity or metabolic issues-related male infertility in the future. IMPORTANCE HFD decreases male fertility via upsetting gut microbiota and transplantation of AOS-benefited gut microbiota (A10-FMT) improves gut microbiota to ameliorate HFD-reduced male fertility. Moreover, A10-FMT improved liver function to benefit the blood metabolome and simultaneously ameliorated the testicular microenvironment to turn the spermatogenesis process on. We demonstrated that AOS-benefited gut microbiota could be applied to treat infertile males with obesity and metabolic issues induced by HFD.

RevDate: 2022-04-21

Zhang WH, Jin ZY, Yang ZH, et al (2022)

Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.

Frontiers in microbiology, 13:818111.

Background: Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects.

Methods: Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6 weeks/over 1 year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition.

Results: Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1 year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT.

Conclusion: Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.

RevDate: 2022-04-20
CmpDate: 2022-04-20

Haifer C, Paramsothy S, Kaakoush NO, et al (2022)

Oral faecal microbiota transplantation in ulcerative colitis - Authors' reply.

The lancet. Gastroenterology & hepatology, 7(4):286-287.

RevDate: 2022-04-20
CmpDate: 2022-04-20

Yuan TY, Rajesh R, M Tan (2022)

Oral faecal microbiota transplantation in ulcerative colitis.

The lancet. Gastroenterology & hepatology, 7(4):286.

RevDate: 2022-04-19
CmpDate: 2022-04-19

Lucarini E, Di Pilato V, Parisio C, et al (2022)

Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence.

Pain, 163(5):861-877.

ABSTRACT: Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions.

RevDate: 2022-04-18

Deng L, Wojciech L, Png CW, et al (2022)

Experimental colonization with Blastocystis ST4 is associated with protective immune responses and modulation of gut microbiome in a DSS-induced colitis mouse model.

Cellular and molecular life sciences : CMLS, 79(5):245.

BACKGROUND: Blastocystis is a common gut protistan parasite in humans and animals worldwide, but its interrelationship with the host gut microbiota and mucosal immune responses remains poorly understood. Different murine models of Blastocystis colonization were used to examine the effect of a common Blastocystis subtype (ST4) on host gut microbial community and adaptive immune system.

RESULTS: Blastocystis ST4-colonized normal healthy mice and Rag1-/- mice asymptomatically and was able to alter the microbial community composition, mainly leading to increases in the proportion of Clostridia vadinBB60 group and Lachnospiraceae NK4A136 group, respectively. Blastocystis ST4 colonization promoted T helper 2 (Th2) response defined by interleukin (IL)-5 and IL-13 cytokine production, and T regulatory (Treg) induction from colonic lamina propria in normal healthy mice. Additionally, we observed that Blastocystis ST4 colonization can maintain the stability of bacterial community composition and induce Th2 and Treg immune responses to promote faster recovery from experimentally induced colitis. Furthermore, fecal microbiota transplantation of Blastocystis ST4-altered gut microbiome to colitis mice reduced the severity of colitis, which was associated with increased production of short-chain fat acids (SCFAs) and anti-inflammatory cytokine IL-10.

CONCLUSIONS: The data confirm our hypothesis that Blastocystis ST4 is a beneficial commensal, and the beneficial effects of Blastocystis ST4 colonization is mediated through modulating of the host gut bacterial composition, SCFAs production, and Th2 and Treg responses in different murine colonization models.

RevDate: 2022-04-18

Debédat J, Le Roy T, Voland L, et al (2022)

The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass.

Gut microbes, 14(1):2050635.

Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.

RevDate: 2022-04-18

Jasiński M, Biliński J, GW Basak (2022)

The Role of the Crosstalk Between Gut Microbiota and Immune Cells in the Pathogenesis and Treatment of Multiple Myeloma.

Frontiers in immunology, 13:853540.

Around 10% of all hematologic malignancies are classified as multiple myeloma (MM), the second most common malignancy within that group. Although massive progress in developing of new drugs against MM has been made in recent years, MM is still an incurable disease, and every patient eventually has relapse refractory to any known treatment. That is why further and non-conventional research elucidating the role of new factors in MM pathogenesis is needed, facilitating discoveries of the new drugs. One of these factors is the gut microbiota, whose role in health and disease is still being explored. This review presents the continuous changes in the gut microbiota composition during our whole life with a particular focus on its impact on our immune system. Additionally, it mainly focuses on the chronic antigenic stimulation of B-cells as the leading mechanism responsible for MM promotion. The sophisticated interactions between microorganisms colonizing our gut, immune cells (dendritic cells, macrophages, neutrophils, T/B cells, plasma cells), and intestinal epithelial cells will be shown. That article summarizes the current knowledge about the initiation of MM cells, emphasizing the role of microorganisms in that process.

RevDate: 2022-04-18

Qu L, Cheng Q, Wang Y, et al (2022)

COPD and Gut-Lung Axis: How Microbiota and Host Inflammasome Influence COPD and Related Therapeutics.

Frontiers in microbiology, 13:868086.

The exact pathogenesis of chronic obstructive pulmonary disease (COPD) remains largely unknown. While current management strategies are effective at stabilizing the disease or relief the symptoms, new approaches are required to target underlying disease process and reverse lung function deterioration. Recent research showed that pneumonia bacteria is critical in disease progression and gut microbiome is likely perturbed in COPD, which is usually accompanied by a decreased intestinal microbial diversity and a disturbance in immune system, contributing to a chronic inflammation. The cross-talk between gut microbes and lungs, termed as the "gut-lung axis," is known to impact immune response and homeostasis in the airway. Although the gut and respiratory microbiota exhibit compositional differences, the gut and lung showed similarities in the origin of epithelia of both gastrointestinal and respiratory tracts, the anatomical structure, and early-life microbial colonization. Evidence showed that respiratory infection might be prevented, or at least dampened by regulating gut microbial ecosystem; thus, a promising yet understudied area of COPD management is nutrition-based preventive strategies. COPD patient is often deficient in nutrient such as antioxidant, vitamins, and fiber intake. However, further larger-scale randomized clinical trials (RCTs) are required to establish the role of these nutrition-based diet in COPD management. In this review, we highlight the important and complex interaction of microbiota and immune response on gut-lung axis. Further research into the modification and improvement of the gut microbiota and new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation is extreme critical to provide new preventive therapies for COPD.

RevDate: 2022-04-18

Hong Y, Zhao J, Chen YR, et al (2022)

Spinal anesthesia alleviates dextran sodium sulfate-induced colitis by modulating the gut microbiota.

World journal of gastroenterology, 28(12):1239-1256.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease with recurrent intestinal inflammation. Although the exact etiology of IBD remains unknown, the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors. The role of the gut microbiota, particularly the bidirectional interaction between the brain and gut microbiota, has gradually attracted more attention.

AIM: To investigate the potential effect of spinal anesthesia on dextran sodium sulfate (DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD.

METHODS: A DSS-induced colitis mice model was established. Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation (FMT) to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved.

RESULTS: We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms, including reduced body weight loss, decreased disease activity index score, improved intestinal permeability and colonic morphology, decreased inflammatory response, and enhanced intestinal barrier functions. Moreover, spinal anesthesia significantly increased the abundance of Bacteroidetes, which was suppressed in the gut microbiota of colitis mice. Interestingly, cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes. We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS, which might affect the gut microbiota.

CONCLUSION: These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota, which highlights a novel approach for the treatment of IBD.

RevDate: 2022-04-18

Xiao W, Su J, Gao X, et al (2022)

The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids.

Microbiome, 10(1):62.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH.

RESULTS: Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO.

CONCLUSION: Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels. Video abstract.

RevDate: 2022-04-18

Adams SM, Close ED, AP Shreenath (2022)

Ulcerative Colitis: Rapid Evidence Review.

American family physician, 105(4):406-411.

Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.

RevDate: 2022-04-18
CmpDate: 2022-04-18

Severyn CJ (2022)

Find a little help from my (microbial) friends.

Cell host & microbe, 30(4):420-422.

Modulation of the microbiota to improve clinical outcomes remains challenging partially because of the large variability in biotherapeutic composition. In this issue of Cell Host & Microbe, Dsouza and colleagues present the phase 1 study results of a defined microbial consortia developed for the prevention of recurrent Clostridioides difficile infection (CDI).

RevDate: 2022-04-15
CmpDate: 2022-04-15

Cheng J, Li W, Wang Y, et al (2022)

Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats.

Microbial biotechnology, 15(3):862-873.

Spinal cord injury (SCI) is a disease involving gastrointestinal disorders. The underlying mechanisms of the potential protective effects of electroacupuncture (EA) and 5-hydroxytryptamine (5-HT) system on SCI remain unknown. We investigated whether EA improves gut microbial dysbiosis in SCI and regulates the 5-HT system. 16S rDNA gene sequencing was applied to investigate alterations in the gut microbiome of the rats. Faecal metabolites and the expression of the 5-HT system were detected. EA and faecal microbiota transplantation (FMT) treatment facilitated intestinal transmission functional recovery and restored the colon morphology of SCI rats. The composition of the intestinal microbiota, including numbers of phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea, were amplified in SCI rats, and EA and FMT significantly reshaped the intestinal microbiota. SCI resulted in disturbed metabolic conditions in rats, and the EA and FMT group showed increased amounts of catechin compared with SCI rats. SCI inhibited 5-HT system expression in the colon, which was significantly reversed by EA and FMT treatment. Therefore, EA may ameliorate SCI by modulating microbiota and metabolites and regulate the 5-HT system. Our study provides new insights into the pathogenesis and therapy of SCI from the perspective of microbiota and 5-HT regulation.

RevDate: 2022-04-14

Dsouza M, Menon R, Crossette E, et al (2022)

Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers.

Cell host & microbe, 30(4):583-598.e8.

Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.

RevDate: 2022-04-14

Asadi A, Shadab Mehr N, Mohamadi MH, et al (2022)

Obesity and gut-microbiota-brain axis: A narrative review.

Journal of clinical laboratory analysis [Epub ahead of print].

INTRODUCTION: Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut-brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms.

MATERIALS AND METHODS: Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies.

RESULTS: The gut-brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus-pituitary-adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity.

CONCLUSION: This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.

RevDate: 2022-04-14

Wang J, Zhang H, He J, et al (2022)

The Role of the Gut Microbiota in the Development of Ischemic Stroke.

Frontiers in immunology, 13:845243.

An increasing number of studies have focused on the gut microbiota and its relationship with various neurological diseases. The gut microbiota can affect the metabolic status of the body, in addition to having an important impact on blood pressure, blood glucose, and atherosclerosis, all of which are risk factors for ischemic stroke. In this review, we summarized studies that included the physiological function of the gut microbiota and gut microbiota disorders related to the central nervous system, thus providing novel ideas for the prevention and treatment of ischemic stroke.

RevDate: 2022-04-12

Bastos RMC, Simplício-Filho A, Sávio-Silva C, et al (2022)

Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease.

International journal of molecular sciences, 23(7): pii:ijms23073842.

Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBRob/ob mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBRob/ob mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.

RevDate: 2022-04-12
CmpDate: 2022-04-12

Lam S, Bai X, Shkoporov AN, et al (2022)

Roles of the gut virome and mycobiome in faecal microbiota transplantation.

The lancet. Gastroenterology & hepatology, 7(5):472-484.

Faecal microbiota transplantation (FMT) is an innovative approach to treat diseases that are associated with gut dysbiosis, by transferring a healthy stool microbiota to a recipient with disease. Beyond the bacteriome, the human gut also harbours diverse communities of viruses and fungi, collectively known as the virome and the mycobiome. The effect of the virome and the mycobiome on the success of FMT therapy has not been appreciated until recently. In this Review, we summarise the current literature on the effects of the gut virome and mycobiome on the treatment of various diseases with FMT. We discuss the beneficial effects and health concerns of viral and fungal transfer during FMT, and highlight the roles of bacteriophages and Candida species in FMT efficacy. We also summarise the intricate relationships between the gut virome, mycobiome, bacteriome, and host immunity underlying FMT effectiveness. Future efforts should be devoted to understanding the versatile roles and the therapeutic mechanisms of viral and fungal lineages, and their combinations, in different diseases. Harnessing the gut virome, mycobiome, and bacteriome in combination is a promising prospect for the future of FMT and microbiota-based therapies.

RevDate: 2022-04-11

Ding D, Yong H, You N, et al (2022)

Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients.

Frontiers in cellular and infection microbiology, 12:820367.

Background: Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.

Methods: We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.

Results: We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family Rikenellaceae and the genus Anaerotruncus (family Ruminococcaceae) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.

Conclusion: Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of Rikenellaceae and Anaerotruncus in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.

RevDate: 2022-04-11

Gao JM, Rao JH, Wei ZY, et al (2022)

Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.

Frontiers in microbiology, 13:876043.

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.

RevDate: 2022-04-11

Fukushima S, Shiotani A, Matsumoto H, et al (2022)

Comparison of mucosa-associated microbiota in Crohn's disease patients with and without anti-tumor necrosis factor-α therapy.

Journal of clinical biochemistry and nutrition, 70(2):182-188.

Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease.

RevDate: 2022-04-11

He Z, Ma Y, Chen X, et al (2022)

Protective Effects of Intestinal Gallic Acid in Neonatal Dairy Calves Against Extended-Spectrum β-lactamase Producing Enteroaggregative Escherichia coli Infection: Modulating Intestinal Homeostasis and Colitis.

Frontiers in nutrition, 9:864080.

Calf diarrhea induced by enteroaggregative E. coli (EAEC) spreads fast among young ruminants, causing continuous hazard to dairy industry. Antimicrobial drug abuse aggravates the incidence rate of multi-drug resistant (MDR) extended-spectrum β-lactamase-producing E. coli (ESBL-EC). However, knowledge of detection and significance of disease-related biomarkers in neonatal female calves are still limited. Gallic acid (GA), a natural secondary metabolite mostly derived from plants, has attracted increasing attention for its excellent anti-inflammatory and anti-oxidative properties. However, it is vague how GA engenders amelioration effects on clinical symptoms and colitis induced by ESBL-EAEC infection in neonatal animals. Here, differentiated gut microbiome and fecal metabolome discerned from neonatal calves were analyzed to ascertain biomarkers in their early lives. Commensal Collinsella and Coriobacterium acted as key microbial markers mediating colonization resistance. In addition, there exists a strongly positive relation between GA, short-chain fatty acid (SCFA) or other prebiotics, and those commensals using random forest machine learning algorithm and Spearman correlation analyses. The protective effect of GA pretreatment on bacterial growth, cell adherence, and ESBL-EAEC-lipopolysaccharide (LPS)-treated Caco-2 cells were first assessed, and results revealed direct antibacterial effects and diminished colonic cell inflammation. Then, oral GA mediated colitis attenuation and recovery of colonic short-chain fatty acid (SCFA) productions on neonatal mice peritonitis sepsis or oral infection model. To corroborate this phenomenon, fecal microbiota transplantation (FMT) method was adopted to remedy the bacterial infection. Of note, FMT from GA-treated neonatal mice achieved profound remission of clinical symptoms and colitis over the other groups as demonstrated by antibacterial capability and prominent anti-inflammatory abilities, revealing improved hindgut microbiota structure with enriched Clostridia_UCG-014, Lachnospiraceae, Oscillospiraceae, and Enterococcaceae, and upregulation of SCFA productions. Collectively, our findings provided the direct evidence of hindgut microbiota and intestinal metabolites, discriminating the health status of neonatal calves post ESBL-EAEC infection. The data provided novel insights into GA-mediated remission of colitis via amelioration of hindgut commensal structure and upregulation of SCFA productions. In addition, its eminent role as potential antibiotic alternative or synergist for future clinic ESBL-EAEC control in livestock.

RevDate: 2022-04-11

Wang X, Tsai T, Zuo B, et al (2022)

Donor age and body weight determine the effects of fecal microbiota transplantation on growth performance, and fecal microbiota development in recipient pigs.

Journal of animal science and biotechnology, 13(1):49.

BACKGROUND: The application of fecal microbiota transplantation (FMT) to improve swine growth performance has been sporadically studied. Most of these studies used a single microbiota source and thus the effect of donor characteristics on recipient pigs' fecal microbiota development and growth performance is largely unknown.

RESULTS: In this study, we collected feces from six donors with heavy (H) or light (L) body weight and different ages (d 42, nursery; d 96, growing; and d 170, finisher) to evaluate their effects on the growth performance and fecal microbiota development of recipient pigs. Generally, recipients that received two doses of FMT from nursery and finisher stages donor at weaning (21 ± 2 days of age) inherited the donor's growth pattern, while the pigs gavaged with grower stage material exerted a numerically greater weight gain than the control pigs regardless of donor BW. FMT from heavier donors (NH, GH, and FH) led to the recipients to have numerically increased growth compared to their lighter counterparts (NL, GL, and FL, respectively) throughout the growing and most finishing stages. This benefit could be attributed to the enrichment of ASV25 Faecalibacterium, ASV61 Faecalibacterium, ASV438 Coriobacteriaceae_unclassified, ASV144 Bulleidia, and ASV129 Oribacterium and decrease of ASV13 Escherichia during nursery stage. Fecal microbiota transplantation from growing and finishing donors influenced the microbial community significantly in recipient pigs during the nursery stage. FMT of older donors' gut microbiota expedited recipients' microbiota maturity on d 35 and 49, indicated by increased estimated microbiota ages. The age-associated bacterial taxa included ASV206 Ruminococcaceae, ASV211 Butyrivibrio, ASV416 Bacteroides, ASV2 Streptococcus, and ASV291 Veillonellaceae. The body weight differences between GL and GH pigs on d 104 were associated with the increased synthesis of the essential amino acid, lysine and methionine, mixed acid fermentation, expedited glycolysis, and sucrose/galactose degradation.

CONCLUSIONS: Overall, our study provided insights into how donor age and body weight affect FMT outcomes regarding growth performance, microbiota community shifts, and lower GI tract metabolic potentials. This study also provided guidance to select qualified donors for future fecal microbiota transplantation.

RevDate: 2022-04-10

Osman M, Budree S, Kelly CR, et al (2022)

Effectiveness and safety of fecal microbiota transplantation for Clostridioides difficile infection: Results from a 5,344 patient cohort study.

Gastroenterology pii:S0016-5085(22)00351-1 [Epub ahead of print].

RevDate: 2022-04-08

Segovia-Rodríguez L, Echeverry-Alzate V, Rincón-Pérez I, et al (2022)

Gut microbiota and voluntary alcohol consumption.

Translational psychiatry, 12(1):146.

Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.

RevDate: 2022-04-08
CmpDate: 2022-04-08

Pérez-Nadales E, Cano Á, Recio M, et al (2022)

Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing Klebsiella pneumoniae (KAPEDIS).

BMJ open, 12(4):e058124 pii:bmjopen-2021-058124.

INTRODUCTION: Infections caused by carbapenemase-producing Enterobacterales are frequent and associated with high rates of mortality. Intestinal carriers are at increased risk of infection by these microorganisms. Decolonisation strategies with antibiotics have not obtained conclusive results. Faecal microbiota transplantation (FMT) could be an effective and safe strategy to decolonise intestinal carriers of KPC-producing Klebsiella pneumoniae (KPC-Kp) but this hypothesis needs evaluation in appropriate clinical trials.

METHODS AND ANALYSIS: The KAPEDIS trial is a single-centre, randomised, double-blind, placebo-controlled, phase 2, superiority clinical trial of FMT for eradication of intestinal colonisation by KPC-Kp. One hundred and twenty patients with rectal colonisation by KPC-Kp will be randomised 1:1 to receive encapsulated lyophilised FMT or placebo. The primary outcome is KPC-Kp eradication at 30 days. Secondary outcomes are: (1) frequency of adverse events; (2) changes in KPC-Kp relative load within the intestinal microbiota at 7, 30 and 90 days, estimated by real-time quantitative PCR analysis of rectal swab samples and (3) rates of persistent eradication, KPC-Kp infection and crude mortality at 90 days. Participants will be monitored for adverse effects throughout the intervention.

ETHICS AND DISSEMINATION: Ethical approval was obtained from Reina Sofía University Hospital Institutional Review Board (approval reference number: 2019-003808-13). Trial results will be published in peer-reviewed journals and disseminated at national and international conferences.



RJR Experience and Expertise


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.


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.


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.


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.


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.


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.


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.


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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A practical handbook on fecal microbiota transplantation (FMT) for physicians, nurses, physician assistants, students, residents, and fellows, The 6 Ds of Fecal Microbiota Transplantation: A Primer from Decision to Discharge and Beyond provides a clinical framework to understand and administer this treatment. FMT has emerged as a promising treatment for C. difficile infection (CDI), and there is a major need for educational resources on the topic. Drs. Jessica Allegretti, Zain Kassam, and their expert contributors are leaders in the field and have collectively cared for thousands of patients suffering from recurrent CDI who have benefitted from FMT. This guide provides practical tools, clinical pearls, and answers to frequently asked questions. Beginning with introductory information on the microbiome and exploring the history of FMT, The 6 Ds of Fecal Microbiota Transplantation outlines a step-by-step checklist for administering FMT: Decision: Who is the right CDI patient to receive FMT? What clinical questions should you ask patients in your FMT clinical assessment?; Donor: How do you select and screen a donor for FMT?; Discussion: What are the risks, benefits, and alternatives that need to be discussed with patients?; Delivery: What is the best delivery method for FMT-colonoscopy, nasogastric tube, enema, or capsules?; Discharge and follow-up: What is the ideal post-FMT care? How should you council patients following FMT?; and Discovery: What are the most promising emerging clinical applications for FMT? What is the evidence for FMT in obesity, autism, irritable bowel syndrome, inflammatory bowel disease, antibiotic resistant bacteria, and liver disease? Arming healthcare professionals with the ability to answer questions from patients regarding FMT and the microbiome, The 6 Ds of Fecal Microbiota Transplantation provides a pragmatic guide for this exciting treatment.

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

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Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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