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30 Mar 2023 at 01:45
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Bibliography on: Fecal Transplantation


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RJR: Recommended Bibliography 30 Mar 2023 at 01:45 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: 2023-03-29

Hao H, Li Z, Qiao SY, et al (2023)

Empagliflozin ameliorates atherosclerosis via regulating the intestinal flora.

Atherosclerosis, 371:32-40 pii:S0021-9150(23)00113-2 [Epub ahead of print].

BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to attenuate atherosclerosis. Further, it has been suggested that intestinal flora influences atherosclerosis progression. Herein we aimed to investigate whether SGLT2i can alleviate atherosclerosis through intestinal flora.

METHODS: Six-week-old male ApoE[-/-] mice fed a high-fat diet were gavaged either empagliflozin (SGLT2i group, n = 9) or saline (Ctrl group, n = 6) for 12 weeks. Feces were collected from both groups at the end of the experiment for fecal microbiota transplantation (FMT). Another 12 six-week-old male ApoE[-/-] mice were fed a high-fat diet and received FMT with feces either from SGLT2i (FMT-SGLT2i group, n = 6) or from Ctrl (FMT-Ctrl group, n = 6) groups. Blood, tissue, and fecal samples were collected for subsequent analyses.

RESULTS: In comparison with Ctrl group, atherosclerosis was less severe in the SGLT2i group (p < 0.0001), and the richness of probiotic, such as f_Coriobacteriaceae, f_S24-7, f_Lachnospiraceae, and f_Adlercreutzia, was higher in feces. Besides, empagliflozin resulted in a significant reduction in the inflammatory response and altered intestinal flora metabolism. Interestingly, compared with FMT-Ctrl, FMT-SGLT2i also showed a reduction in atherosclerosis and systemic inflammatory response, as well as changes in the component of intestinal flora and pertinent metabolites similar to SGLT2i group.

CONCLUSIONS: Empagliflozin seems to mitigate atherosclerosis partly by regulating intestinal microbiota, and this anti-atherosclerotic effect can be transferred through intestinal flora transplantation.

RevDate: 2023-03-29

Chen LA, Oliva-Hemker M, Radin A, et al (2023)

Longitudinal bile acid composition changes following fecal microbiota transplantation for Clostridioides difficile infection in children with and without underlying inflammatory bowel disease.

Journal of Crohn's & colitis pii:7093088 [Epub ahead of print].

BACKGROUND AND AIMS: Fecal microbiota transplant (FMT) is effective in treating recurrent Clostridioides difficile infection (CDI) and restores gut microbiota composition. This unlikely accounts for its entire mechanism of efficacy, as studies have shown that factors such as bile acids influence the risk of infection by affecting Clostridioides difficile germination. We therefore aimed to investigate longitudinal changes in the gut bile acid composition after FMT performed for recurrent CDI, in children with and without inflammatory bowel disease (IBD).

METHODS: Eight children received FMT; five had underlying IBD. Primary and secondary fecal bile acids were measured by liquid chromatography-mass spectrometry in recipients (pre-FMT and longitudinally post-FMT for up to 6 months) and donors.

RESULTS: Pre-FMT, recipients had higher primary and lower secondary bile acid proportions compared with donors. Post-FMT, there was a gradual increase of secondary and decrease of primary bile acids. While gut bacterial diversity had been shown to be restored in all children shortly after FMT, normalization of bile acids to donor levels occurred only by 6 months. In children with IBD, although microbiota diversity returned to pre-FMT levels within 6 months, secondary bile acids remained at donor levels.

CONCLUSIONS: The differences in bile acid profiles compared to gut bacterial diversity post-FMT suggests that interactions between the two may be more complex than previously appreciated and may contribute to FMT efficacy in different ways. This initial finding demonstrates the need to further investigate gut metabolites in larger cohorts with longitudinal sampling to understand the mechanisms of FMT effectiveness.

RevDate: 2023-03-29

Dossaji Z, Khattak A, Tun KM, et al (2023)

Efficacy of Fecal Microbiota Transplant on Behavioral and Gastrointestinal Symptoms in Pediatric Autism: A Systematic Review.

Microorganisms, 11(3): pii:microorganisms11030806.

Background and Aims: There is a high prevalence of gastrointestinal-related (GI) symptoms among children with autism spectrum disorder (ASD), which is associated with the severity of behavioral symptoms. Fecal microbiota transplantation (FMT) is a proposed therapeutic strategy that aims to address the dysregulation of the gut microbiome among children with ASD. Our study performed the first systematic review aimed to evaluate the benefits of FMT on the behavioral and gastrointestinal symptoms of pediatric patients with autism. Methods: A literature search was performed using variations of the keywords "pediatrics" and "fecal microbiota transplantation" in PubMed, EMBASE, CINAHL, Cochrane, and Web of Science from inception to 30 June 2022. Four studies that met the eligibility criteria were included in the systematic review. The efficacy of FMT on behavioral symptoms was measured by the difference in Aberrant Behavior Checklist (ABC) and Child Autism Rating Scale (CARS) scores before and after FMT. Results: We found a statistically significant improvement (p < 0.05) in ABC and CARS scores following FMT, with a statistically significant decrease in scores observed across all studies. In addition, substantial improvements in gastrointestinal symptoms were observed across all studies. Conclusion: Our findings suggest that FMT may offer a promising intervention for treating both behavioral and gastrointestinal symptoms in pediatric patients with autism.

RevDate: 2023-03-29

Zhang Z, Chen H, Huang J, et al (2023)

Early Administration of Vancomycin Inhibits Pulmonary Embolism by Remodeling Gut Microbiota.

Journal of personalized medicine, 13(3): pii:jpm13030537.

Pulmonary embolism (PE) is a common and potentially fatal condition in the emergency department, and early identification of modifiable risk factors for prevention and management is highly desirable. Although gut dysbiosis is associated with a high incidence of venous thromboembolism, the role and mechanisms of the gut microbiome in the pathogenesis of venous thromboembolism, especially PE, remain unexplored. Here, we attempted to elucidate the benefits of the gut microbiome in the pathogenesis of PE using multiple antibiotics and fecal microbiota transplantation (FMT) for early intervention in a classical mouse model of PE. The results showed that early administration of various antibiotics (except ampicillin) could inhibit pulmonary thrombosis to a certain extent and reduced mortality in young and old mice with PE. Among them, vancomycin has the best inhibitory effect on PE. With the help of gut microbiota sequencing analysis, we found that antibiotic treatment can reshape the gut microbiota; especially vancomycin can significantly improve the gut microbiota structure in PE mice. Furthermore, FMT could transfer vancomycin-modified gut microbes into mice and inhibit the pathogenesis of PE, possibly due to increased intestinal colonization by Parasutterella. These data elucidate the underlying molecular mechanism by which early administration of vancomycin can remodel the gut microbiota to suppress PE, providing new clues for clinical optimization and development of PE prevention strategies.

RevDate: 2023-03-29

Palumbo VD, Tutino R, Messina M, et al (2023)

Altered Gut Microbic Flora and Haemorrhoids: Could They Have a Possible Relationship?.

Journal of clinical medicine, 12(6): pii:jcm12062198.

To date, the exact pathophysiology of haemorrhoids is poorly understood. The different philosophies on haemorrhoids aetiology may lead to different approaches of treatment. A pathogenic theory involving a correlation between altered anal canal microflora, local inflammation, and muscular dyssynergia is proposed through an extensive review of the literature. Since the middle of the twentieth century, three main theories exist: (1) the varicose vein theory, (2) the vascular hyperplasia theory, and (3) the concept of a sliding anal lining. These phenomena determine changes in the connective tissue (linked to inflammation), including loss of organization, muscular hypertrophy, fragmentation of the anal subepithelial muscle and the elastin component, and vascular changes, including abnormal venous dilatation and vascular thrombosis. Recent studies have reported a possible involvement of gut microbiota in gut motility alteration. Furthermore, dysbiosis seems to represent the leading cause of bowel mucosa inflammation in any intestinal district. The alteration of the gut microbioma in the anorectal district could be responsible for haemorrhoids and other anorectal disorders. A deeper knowledge of the gut microbiota in anorectal disorders lays the basis for unveiling the roles of these various gut microbiota components in anorectal disorder pathogenesis and being conductive to instructing future therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in anorectal disorders.

RevDate: 2023-03-29

Mareschal J, Hemmer A, Douissard J, et al (2023)

Surgical Prehabilitation in Patients with Gastrointestinal Cancers: Impact of Unimodal and Multimodal Programs on Postoperative Outcomes and Prospects for New Therapeutic Strategies-A Systematic Review.

Cancers, 15(6): pii:cancers15061881.

The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.

RevDate: 2023-03-29

Piccioni A, Rosa F, Mannucci S, et al (2023)

Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship.

Biomedicines, 11(3): pii:biomedicines11030707.

There is much evidence confirming the crucial role played by the gut microbiota in modulating the immune system in the onset of autoimmune diseases. In this article, we focus on the relationship between alterations in the microbiome and the onset of diabetes mellitus type 1 and LADA, in light of the latest evidence. We will then look at both how the role of the gut microbiota appears to be increasingly crucial in the pathogenesis of these disorders and how this aspect may be instrumental in the development of new potential therapeutic strategies that modulate the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation.

RevDate: 2023-03-28

Balzano T (2023)

Active Clinical Trials in Hepatic Encephalopathy: Something Old, Something New and Something Borrowed.

Neurochemical research [Epub ahead of print].

Hepatic encephalopathy (HE) is a potentially reversible neurocognitive syndrome that occurs in patients with acute or chronic liver disease. Currently, most of the therapies for HE aim to reduce ammonia production or increase its elimination. To date, only two agents have been approved as treatments for HE: lactulose and rifaximin. Many other drugs have also been used, but data to support their use are limited, preliminary or lacking. The aim of this review is to provide an overview and discussion of the current development of treatments for HE. Data from ongoing clinical trials in HE were obtained from the ClinicalTrials.gov website, and a breakdown analysis of studies that were active on August 19th, 2022, was performed. Seventeen registered and ongoing clinical trials for therapeutics targeting HE were identified. More than 75% of these agents are in phase II (41.2%) or in phase III (34.7%). Among them, there are many old acquaintances in the field, such as lactulose and rifaximin, some new entries such as fecal microbiota transplantation and equine anti-thymocyte globulin, an immunosuppressive agent, but also some therapies borrowed from other conditions, such as rifamycin SV MMX and nitazoxanide, two antimicrobial agents FDA approved for the treatment of some types of diarrheas or VE303 and RBX7455, two microbiome restoration therapies, currently used as treatment of high-risk Clostridioides difficile infections. If working, some of these drugs could soon be used as valid alternatives to current therapies when ineffective or be approved as novel therapeutic approaches to improve the quality of life of HE patients.

RevDate: 2023-03-28

Dang Z, Gao M, Wang L, et al (2023)

Synthetic bacterial therapies for intestinal diseases based on quorum- sensing circuits.

Biotechnology advances pii:S0734-9750(23)00049-6 [Epub ahead of print].

Bacterial therapy has become a key strategy against intestinal infectious diseases in recent years. Moreover, regulating the gut microbiota through traditional fecal microbiota transplantation and supplementation of probiotics faces controllability, efficacy, and safety challenges. The infiltration and emergence of synthetic biology and microbiome provide an operational and safe treatment platform for live bacterial biotherapies. Synthetic bacterial therapy can artificially manipulate bacteria to produce and deliver therapeutic drug molecules. This method has the advantages of solid controllability, low toxicity, strong therapeutic effects, and easy operation. As an essential tool for dynamic regulation in synthetic biology, quorum sensing (QS) has been widely used for designing complex genetic circuits to control the behavior of bacterial populations and achieve predefined goals. Therefore, QS-based synthetic bacterial therapy might become a new direction for the treatment of diseases. The pre-programmed QS genetic circuit can achieve a controllable production of therapeutic drugs on particular ecological niches by sensing specific signals released from the digestive system in pathological conditions, thereby realizing the integration of diagnosis and treatment. Based on this as well as the modular idea of synthetic biology, QS-based synthetic bacterial therapies are divided into an environmental signal sensing module (senses gut disease physiological signals), a therapeutic molecule producing module (plays a therapeutic role against diseases), and a population behavior regulating module (QS system). This review article summarized the structure and function of these three modules and discussed the rational design of QS gene circuits as a novel intervention strategy for intestinal diseases. Moreover, the application prospects of QS-based synthetic bacterial therapy were summarized. Finally, the challenges faced by these methods were analyzed to make the targeted recommendations for developing a successful therapeutic strategy for intestinal diseases.

RevDate: 2023-03-28

Madden GR, Rigo I, Boone R, et al (2023)

Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection.

Infection and immunity [Epub ahead of print].

Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective therapies (i.e., fecal transplant, fidaxomicin, bezlotoxumab). We used a biorepository of 257 hospitalized patients with 24 features collected at diagnosis, including 17 plasma cytokines, total/neutralizing anti-toxin B IgG, stool toxins, and PCR cycle threshold (CT) (a proxy for stool organism burden). The best set of predictors for recurrent infection was selected by Bayesian model averaging for inclusion in a final Bayesian logistic regression model. We then used a large PCR-only data set to confirm the finding that PCR CT predicts recurrence-free survival using Cox proportional hazards regression. The top model-averaged features were (probabilities of >0.05, greatest to least): interleukin 6 (IL-6), PCR CT, endothelial growth factor, IL-8, eotaxin, IL-10, hepatocyte growth factor, and IL-4. The accuracy of the final model was 0.88. Among 1,660 cases with PCR-only data, cycle threshold was significantly associated with recurrence-free survival (hazard ratio, 0.95; P < 0.005). Certain biomarkers associated with C. difficile infection severity were especially important for predicting recurrence; PCR CT and markers of type 2 immunity (endothelial growth factor [EGF], eotaxin) emerged as positive predictors of recurrence, while type 17 immune markers (IL-6, IL-8) were negative predictors. In addition to novel serum biomarkers (particularly, IL-6, EGF, and IL-8), the readily available PCR CT may be critical to augment underperforming clinical models for C. difficile recurrence.

RevDate: 2023-03-28

Fan X, Mai C, Zuo L, et al (2023)

Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice.

Acta pharmaceutica Sinica. B, 13(3):1164-1179.

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10[+] M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10[+] M2 macrophage production.

RevDate: 2023-03-28

Tian H, Wang J, Feng R, et al (2023)

Efficacy of faecal microbiota transplantation in patients with progressive supranuclear palsy-Richardson's syndrome: a phase 2, single centre, randomised clinical trial.

EClinicalMedicine, 58:101888.

BACKGROUND: Faecal microbiota transplantation (FMT) has demonstrated efficacy in treating gastrointestinal (GI) diseases, such as Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). GI dysfunction is a frequent and occasionally dominating symptom of progressive supranuclear palsy-Richardson's syndrome (PSP-RS). However, it is not known whether FMT has clinical efficacy for PSP-RS.

METHODS: This 36-week, randomised, placebo-controlled, parallel-group, phase 2 clinical trial was performed at a university tertiary referral hospital in China. From August 15 2021 to December 31 2021, a total of 68 newly diagnosed patients with PSP-RS (male 40 [59%], female 28 [41%]) who had never received any antiparkinsonian medications were enrolled and randomly assigned to receive either healthy donor FMT (n = 34, FMT group) or a mixture of 0.9% saline and food colouring (E150c) as sham transplantation (n = 34, placebo group) through transendoscopic enteral tubing (TET). Two days after oral antibiotics, participants received 1 week of transplantation. After an interval of 4 weeks, retransplantation was performed. Then, the last transplantation was given after another interval of 4 weeks, and the participants were followed up for 24 weeks (week 36). Clinicaltrials.gov identifier: ChiCTR-2100045397.

FINDINGS: Among 68 patients who were randomised (mean age, 67.2 (SD 5.1); 40 [59%] were male, 28 [41%] were female), 63 participants completed the trial. Efficacy analyses were performed on the intention-to-treat (ITT) analysis set. At week 16, the mean PSP Rating Scale (PSPRS) scores (the primary outcome) improved from 40.1 (SD 7.6) to 36.9 (SD 5.9) in the FMT group, whereas the scores changed from 40.1 (SD 6.9) to 41.7 (SD 6.2) in the placebo group, for a treatment benefit of 4.3 (95% CI, 3.2-5.4) (P < 0.0001). After 3-cycle intervention, symptoms of constipation, depression, and anxiety (the secondary outcome) improved significantly at week 16 in the FMT group compared with the placebo group, the majority of which were maintained at the 24-week follow-up (week 36).

INTERPRETATION: Our findings suggest that, compared with placebo, FMT treatment significantly improved motor and nonmotor symptoms in patients with PSP-RS, as well as reduced intestinal inflammation and enhanced the intestinal barrier by regulating the intestinal microbiota composition.

FUNDING: The National Natural Science Foundation of China (No. 82122022, 82171248, 81873791, and 82230084), Natural Science Foundation of Henan Province for Excellent Young Scholars (no. 202300410357), and Henan Province Young and Middle-Aged Health Science and Technology Innovation Talent Project (YXKC2020033).

RevDate: 2023-03-27

Garey KW, Feuerstadt P, Dubberke ER, et al (2023)

Effect of fecal microbial transplantation on Clostridioides difficile infection: dysbiosis, metabolites and health related quality of life.

Open forum infectious diseases, 10(3):ofad113 pii:ofad113.

RevDate: 2023-03-27

Tucker EC, Haylock-Jacobs S, Rapaic M, et al (2023)

Stool donor screening within a Therapeutic Goods Administration compliant donor screening program for fecal microbiota transplantation.

JGH open : an open access journal of gastroenterology and hepatology, 7(3):172-177.

BACKGROUND AND AIM: This study evaluates whether a stool donor program to supply fecal microbiota transplantation (FMT) product is feasible in the Australian regulatory environment. The primary outcome was capacity to supply FMT product. The secondary outcomes were donor eligibility, retention, and output.

METHODS: Prospective observational cohort study using data collected from the stool donor and FMT production records from BiomeBank, South Australia. Participants were people who engaged with BiomeBank's donor screening and FMT manufacturing process between 01 January 2021 and 31 December 2021.

RESULTS: In total 176 people registered interest in the program, 74 of 176 (42.0%) proceeded to written questionnaire, 14 of 176 (8.0%) underwent clinical assessment, and 8 of 176 (4.5%) enrolled in the program. Two people were ineligible based on laboratory tests: both had an extended spectrum beta-lactamase producing organism in stool and one also tested positive for hepatitis B core antibody. Two donors remained eligible from 2020, resulting in 10 enrolled donors in 2021; 5 of 10 (50%) male with a median age of 36.9 years (interquartile range, 30.3-42.7 years). All donors were ineligible to donate at some time point. There were 144 stool donations processed into 1480 50 mL FMT; 413 FMT were shipped to 33 Australian hospitals for treatment, 470 for clinical trials, and 89 were destroyed prior to release from quarantine.

CONCLUSION: Recruitment into the program, retention, and maximizing the yield from a donation period was challenging. Despite this, BiomeBank was able to produce and supply FMT to Australian hospitals under the TGA-regulated Class 2 Biologicals framework.

RevDate: 2023-03-27

Philips CA (2023)

"Seek and find" or "search and destroy?" Identifying and retaining "healthy" stool donors for fecal microbiota transplantation.

JGH open : an open access journal of gastroenterology and hepatology, 7(3):169-171.

RevDate: 2023-03-25

Xu X, Li G, Zhang D, et al (2023)

Gut Microbiota is Associated with Aging-Related Processes of a Small Mammal Species under High-Density Crowding Stress.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

Humans and animals frequently encounter high-density crowding stress, which may accelerate their aging processes; however, the roles of gut microbiota in the regulation of aging-related processes under high-density crowding stress remain unclear. In the present study, it is found that high housing density remarkably increases the stress hormone (corticosterone), accelerates aging-related processes as indicated by telomere length (in brain and liver cells) and DNA damage or inflammation (as revealed by tumor necrosis factor-α and interleukin-10 levels), and reduces the lifespan of Brandt's vole (Lasiopodomys brandtii). Fecal microbiota transplantation from donor voles of habitats with different housing densities induces similar changes in aging-related processes in recipient voles. The elimination of high housing density or butyric acid administration delays the appearance of aging-related markers in the brain and liver cells of voles housed at high-density. This study suggests that gut microorganisms may play a significant role in regulating the density-dependent aging-related processes and subsequent population dynamics of animals, and can be used as potential targets for alleviating stress-related aging in humans exposed to high-density crowding stress.

RevDate: 2023-03-24

Liu L, Wang H, Chen X, et al (2023)

Gut microbiota and its metabolites in depression: from pathogenesis to treatment.

EBioMedicine, 90:104527 pii:S2352-3964(23)00092-0 [Epub ahead of print].

Major depressive disorder is one of the most disabling mental disorders worldwide. Increasing preclinical and clinical studies have highlighted that compositional and functional (e.g., metabolite) changes in gut microbiota, known as dysbiosis, are associated with the onset and progression of depression via regulating the gut-brain axis. However, the gut microbiota and their metabolites present a double-edged sword in depression. Dysbiosis is involved in the pathogenesis of depression while, at the same time, offering a novel therapeutic target. In this review, we describe the association between dysbiosis and depression, drug-microbiota interactions in antidepressant treatment, and the potential health benefits of microbial-targeted therapeutics in depression, including dietary interventions, fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and postbiotics. With the emergence of microbial research, we describe a new direction for future research and clinical treatment of depression.

RevDate: 2023-03-24

Nöltner C, Bulashevska A, Hübscher K, et al (2023)

Fecal Immunoglobulin Levels as a Modifier of the Gut Microbiome in Patients with Common Variable Immunodeficiency.

Journal of clinical immunology [Epub ahead of print].

OBJECTIVE: Common variable immunodeficiency (CVID) is the most common clinically relevant entity of inborn errors of immunity. In these patients, an altered gut microbiome composition with reduced diversity has been described. We sought to investigate the fecal immunoglobulin levels and their impact on the gut microflora in patients with CVID.

METHODS: We analyzed the gut microbiome of 28 CVID patients and 42 healthy donors (HDs), including 21 healthy household controls, by sequencing the V3 and V4 regions of the bacterial 16S rRNA gene extracted from stool samples. The fecal levels of immunoglobulin A, M, and G of 27 CVID patients and 41 HDs were measured in the supernatant by ELISA and normalized for protein concentration.

RESULTS: We measured decreased IgA and increased IgG in stool samples from CVID patients compared to HDs. Decreased levels of fecal IgA and IgM were associated with reduced microbial diversity and increased dysbiosis. We identified a large number of significantly differentially abundant taxa, especially in patients with decreased IgA levels, but also in patients with decreased IgM levels compared to their counterparts.

CONCLUSIONS: CVID patients have an altered gut microbiota composition, which is most prevalent in patients with decreased fecal IgA and IgM levels. In this study, we identify fecal immunoglobulins as a potential modifier of the gut microbiome in CVID patients.

RevDate: 2023-03-23

Xu X, Zhuo L, Zhang L, et al (2023)

Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation.

Psychiatry research, 323:115172 pii:S0165-1781(23)00123-3 [Epub ahead of print].

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate the α2-adrenoceptor. Treatment with α2-adrenergic agonists in patients with ADHD is becoming increasingly common. However, the therapeutic potential of DEX for the treatment of ADHD is unknown. Here, we evaluated the effect of DEX on ADHD-like behavior in spontaneously hypertensive rats (SHRs), a widely used animal model of ADHD. DEX treatment ameliorated hyperactivity and spatial working memory deficits and normalized θ electroencephalogram (EEG) rhythms in SHRs. We also found that DEX treatment altered the gut microbiota composition and promoted the enrichment of beneficial gut bacterial genera associated with anti-inflammatory effects in SHRs. The gut pathological scores and permeability and the level of inflammation observed in the gut and brain were remarkably improved after DEX administration. Moreover, transplantation of fecal microbiota from DEX-treated SHRs produced effects that mimicked the therapeutic effects of DEX administration. Therefore, DEX is a promising treatment for ADHD that functions by reshaping the composition of the gut microbiota and reducing inflammation in the gut and brain.

RevDate: 2023-03-23

Stoff R, Wolf Y, B Boursi (2023)

Fecal Microbiota Transplantation as a Cancer Therapeutic.

Cancer journal (Sudbury, Mass.), 29(2):102-108.

For decades, cancer research and treatment focused on the cellular level, viewing cancer as a genetic disease of cell transformation. In the era of chemotherapy and radiotherapy, studies from the second half of the 19th century suggesting an association between the microbiota and cancer were almost neglected. The main focus of the field was limited to identification of specific viruses and bacteria that may serve as direct carcinogens leading to the recognition of 7 viruses (i.e., human papillomavirus, hepatitis B virus, and Kaposi sarcoma-associated herpesvirus) and 1 bacterium (Helicobacter pylori) as human carcinogens by the International Agency for Research on Cancer (https://monographs.iarc.who.int/agents-classified-by-the-iarc/). Shortly after the publication of the first draft of the human genome project in February 2001, the Nobel laureate microbiologist Joshua Lederberg raised the question: "Is human identity all in the genes?" It took more than a decade later and the development of multiomic techniques to confirm that his answer "each one of us is a small ecological community" was correct (Lederberg J. Keynote Address: Beyond the Genome. Brooklyn Law Rev 67). This ecological notion became relevant to cancer prevention, prediction, and treatment following the immunotherapy revolution and the understanding of the metabolic and immunologic roles of the microbiota in health and disease. Recently, the microbiota was recognized as an emerging hallmark of cancer following a large body of research showing its role in tumorigenesis, treatment efficacy and toxicity, and initial data regarding the role of microbial modulation in cancer therapy (Cancer Discov 2022;12(1):31-46). In the current review, we will focus on the role of fecal microbiota transplantation, the first microbial modulation technique that is used mainly in low-complexity conditions such as recurrent Clostridium difficile infections (Aliment Pharmacol Ther 2017;46(5):479-493), as a possible cancer therapeutic. However, to better understand the suggested roles of fecal microbiota transplantation in medical oncology, we first need to understand cancer as an ecological niche and the role of the microbiota in tumorigenesis and cancer treatment, specifically immunotherapy.

RevDate: 2023-03-23

Malard F, RR Jenq (2023)

The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation.

Cancer journal (Sudbury, Mass.), 29(2):75-83.

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes.In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.

RevDate: 2023-03-23

Myojin Y, TF Greten (2023)

The Microbiome and Liver Cancer.

Cancer journal (Sudbury, Mass.), 29(2):57-60.

The gut microbiome and liver are anatomically and functionally connected. The impact of the gut microbiota or microbial metabolites on liver cancer progression via immune cells has been recently revealed across various preclinical models. Commensal gut microbes of liver cancer patients differ from control subjects, and their composition is affected by the etiology of the hepatocellular carcinoma. The gut microbiota represents a potential novel target for intervention as shown in patients with melanoma, but we still lack data in patients with hepatocellular carcinoma. Fecal microbiota transplantation and dietary approaches may improve immunotherapy efficacy, and a couple of clinical trials are ongoing. In liver cancer, the ongoing recognition of interactions between gut microbes and the tumor immune microenvironment provides an exciting therapeutic avenue to complement established immunotherapy.

RevDate: 2023-03-23

Yang Q, Wang B, Zheng Q, et al (2023)

A Review of Gut Microbiota-Derived Metabolites in Tumor Progression and Cancer Therapy.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

Gut microbiota-derived metabolites are key hubs connecting the gut microbiome and cancer progression, primarily by remodeling the tumor microenvironment and regulating key signaling pathways in cancer cells and multiple immune cells. The use of microbial metabolites in radiotherapy and chemotherapy mitigates the severe side effects from treatment and improves the efficacy of treatment. Immunotherapy combined with microbial metabolites effectively activates the immune system to kill tumors and overcomes drug resistance. Consequently, various novel strategies have been developed to modulate microbial metabolites. Manipulation of genes involved in microbial metabolism using synthetic biology approaches directly affects levels of microbial metabolites, while fecal microbial transplantation and phage strategies affect levels of microbial metabolites by altering the composition of the microbiome. However, some microbial metabolites harbor paradoxical functions depending on the context (e.g., type of cancer). Furthermore, the metabolic effects of microorganisms on certain anticancer drugs such as irinotecan and gemcitabine, render the drugs ineffective or exacerbate their adverse effects. Therefore, a personalized and comprehensive consideration of the patient's condition is required when employing microbial metabolites to treat cancer. The purpose of this review is to summarize the correlation between gut microbiota-derived metabolites and cancer, and to provide fresh ideas for future scientific research.

RevDate: 2023-03-23

Dong D, Su T, Chen W, et al (2023)

Clostridioides difficile aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment.

Gut microbes, 15(1):2192478.

Clostridioides difficile is a pathogen contributing to increased morbidity and mortality of patients with inflammatory bowel disease (IBD). To determine how C. difficile affects the severity of colitis, we constructed a dextran sulfate solution-induced colitis model challenged with C. difficile. Without antibiotic administration, C. difficile led to transient colonization in mice with colitis, but still significantly enhanced disease severity as assessed by weight loss, histopathological damages, and inflammatory cytokine concentrations. Because this effect is independent of toxin production as shown by infection with a non-toxigenic strain, we focused on changes in the gut microbiota. The microbiota altered by C.difficile, featured with reduced proportions of g_Prevotellaceae_UCG-001 and g_Muribaculaceae, were confirmed to contribute to disease severity in colitis mice via fecal microbiota transplantations. The inflamed colon showed neutrophil accumulation by flow cytometric analysis and myeloperoxidase immunochemical staining. There was enrichment of upregulated genes in leukocyte chemotaxis or migration as shown by RNA sequencing analysis. The isolated neutrophils from C. difficile-infected mice with colitis showed a robust migratory ability and had enhanced expression of cytokines and chemokines. We observed a detrimental role of neutrophils in the progress of disease by hindering neutrophil recruitment with the CXCR2 inhibitor SB225002. Furthermore, neutrophil recruitment appeared to be regulated by interleukin (IL)-1β, as inhibition of IL-1β production by MCC950 markedly ameliorated inflammation with decreased neutrophil accumulation and neutrophil-derived chemokine expression. In conclusion, our study provides information on the complicated interaction between microbiota and immune responses in C. difficile-induced inflammation in mice with colitis. Our findings could help determine potential therapeutic targets for patients with IBD concurrent with C. difficile infection.

RevDate: 2023-03-23

Kim IB, Park SC, YK Kim (2023)

Microbiota-Gut-Brain Axis in Major Depression: A New Therapeutic Approach.

Advances in experimental medicine and biology, 1411:209-224.

Major depression is impacted by the disruption of gut microbiota. Defects in gut microbiota can lead to microbiota-gut-brain axis dysfunction and increased vulnerability to major depression. While traditional chemotherapeutic approaches, such as antidepressant use, produce an overall partial therapeutic effect on depression, the gut microbiome has emerged as an effective target for better therapeutic outcomes. Recent representative studies on the microbiota hypothesis to explore the association between gut pathophysiology and major depression have indicated that restoring gut microbiota and microbiota-gut-brain axis could alleviate depression. We reviewed studies that supported the gut microbiota hypothesis to better understand the pathophysiology of depression; we also explored reports suggesting that gut microbiota restoration is an effective approach for improving depression. These findings indicate that gut microbiota and microbiota-gut-brain axis are appropriate new therapeutic targets for major depression.

RevDate: 2023-03-23

Evrensel A (2023)

Microbiome-Induced Autoimmunity and Novel Therapeutic Intervention.

Advances in experimental medicine and biology, 1411:71-90.

Microorganisms' flora, which colonize in many parts of our body, stand out as one of the most important components for a healthy life. This microbial organization called microbiome lives in integration with the body as a single and whole organ/system. Perhaps, the human first encounters the microbial activity it carries through the immune system. This encounter and interaction are vital for the development of immune system cells that protect the body against pathogenic organisms and infections throughout life. In recent years, it has been determined that some disruptions in the host-microbiome interaction play an important role in the physiopathology of autoimmune diseases. Although the details of this interaction have not been clarified yet, the focus is on leaky gut syndrome, dysbiosis, toll-like receptor ligands, and B cell dysfunction. Nutritional regulations, prebiotics, probiotics, fecal microbiota transplantation, bacterial engineering, and vaccination are being investigated as new therapeutic approaches in the treatment of problems in these areas. This article reviews recent research in this area.

RevDate: 2023-03-23

Shin C, YK Kim (2023)

Microbiota-Gut-Brain Axis: Pathophysiological Mechanism in Neuropsychiatric Disorders.

Advances in experimental medicine and biology, 1411:17-37.

Gut microbiota influence human behavior. The immunological, metabolic, and endocrine systems are involved in bidirectional communication between the gut and the brain, which is regulated by microbes through the microbiota-derived neurochemicals and metabolites. Gut microbiota have certain effects on neurodevelopment and maturation of immunity. However, gut dysbiosis can lead to neuropsychiatric disorders. Animal research and clinical case-control studies have demonstrated that gut dysbiosis has an adverse effect on human behavior through a variety of mechanisms. Recent meta-analysis on clinical studies confirmed gut dysbiosis in several major neuropsychiatric disorders. Microbiota-targeted intervention has recently been in the spotlight and meta-analyses have confirmed its effectiveness. In this chapter, we summarize the evidence for the interactions between microbiota and brain-gut network, as well as the potential pathophysiological mechanisms involved.

RevDate: 2023-03-22

Mishra SP, Wang B, Jain S, et al (2023)

A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut.

Gut pii:gutjnl-2022-327365 [Epub ahead of print].

OBJECTIVE: Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability ('leaky gut') in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive.

DESIGN: In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism.

RESULTS: We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA-miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 (Zo1) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/miR-101a/Zo1 axis.

CONCLUSION: Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities.


RevDate: 2023-03-23
CmpDate: 2023-03-23

Oh M, L Zhang (2023)

DeepGeni: deep generalized interpretable autoencoder elucidates gut microbiota for better cancer immunotherapy.

Scientific reports, 13(1):4599.

Recent studies revealed that gut microbiota modulates the response to cancer immunotherapy and fecal microbiota transplantation has clinical benefits in melanoma patients during treatment. Understanding how microbiota affects individual responses is crucial for precision oncology. However, it is challenging to identify key microbial taxa with limited data as statistical and machine learning models often lose their generalizability. In this study, DeepGeni, a deep generalized interpretable autoencoder, is proposed to improve the generalizability and interpretability of microbiome profiles by augmenting data and by introducing interpretable links in the autoencoder. DeepGeni-based machine learning classifier outperforms state-of-the-art classifier in the microbiome-driven prediction of responsiveness of melanoma patients treated with immune checkpoint inhibitors. Moreover, the interpretable links of DeepGeni elucidate the most informative microbiota associated with cancer immunotherapy response. DeepGeni not only improves microbiome-driven prediction of immune checkpoint inhibitor responsiveness but also suggests potential microbial targets for fecal microbiota transplant or probiotics improving the outcome of cancer immunotherapy.

RevDate: 2023-03-21

Kharofa J, Haslam D, Wilkinson R, et al (2023)

Analysis of the fecal metagenome in long-term survivors of pancreas cancer.

Cancer [Epub ahead of print].

BACKGROUND: The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described.

METHODS: In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n = 16). LTS was defined as >4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls.

RESULTS: All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4-14 years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia mucinophilia species.

CONCLUSIONS: Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia mucinophilia. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.

PLAIN LANGUAGE SUMMARY: Although pancreatic cancer treatments have improved, the number of long-term survivors has remained stagnant with a 5-year overall survival estimate of 9%. Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system. In this study, we profiled the stool microbiome in long-term survivors of pancreas cancer and controls. Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia mucinophilia. These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.

RevDate: 2023-03-21

Shi YT, He JM, Tong ZA, et al (2023)

Ligature-Induced Periodontitis Drives Colorectal Cancer: An Experimental Model in Mice.

Journal of dental research [Epub ahead of print].

Periodontitis is a prevalent inflammatory oral disease associated with an increased risk of colorectal cancer. Experimental animal models are critical tools to investigate the effects and mechanisms of periodontitis on colorectal cancer. Several murine periodontitis models have been used in research, including oral gavage, periodontal pathogen injection, and ligature models. The role of experimental periodontitis caused by silk ligation in colorectal cancer remains unclear. In this study, we used an experimental periodontitis model on a colitis-associated colorectal cancer model and a spontaneous model, respectively. We observed the promotion of colorectal cancer in ligature-induced periodontitis mice compared to those control mice in 2 different models, as assessed by tumor number, tumor size, and tumor load. Since bacterial dysbiosis is an important feature of periodontitis, we next analyzed the oral and gut microbiomes using 16S ribosomal RNA gene sequencing. We found that the experimental periodontitis model reshaped the microbial community in the oral cavity and gut. In addition, we found a higher extent of programmed death 1 (PD-1)-positive CD8[+] T-cell infiltration in tumor samples of the periodontitis group than in controls by immunofluorescence staining. Regarding the potential molecular mechanism, we transplanted the fecal microbiota of the periodontitis patient into mice and observed a tumor-promoting effect in the periodontitis group, assessed by tumor volume and tumor weight, together with a low level of INF-γ[+] CD8[+] T-cell infiltration in subcutaneous tumor mice. Taken together, we show that ligature-induced periodontitis model promotes colorectal cancer by microbiota remodeling and suppression of the immune response.

RevDate: 2023-03-20

Jiang S, B Shen (2023)

[Research progress on the relationship between gut microbiota dysbiosis and osteoarthritis].

Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery, 37(3):371-376.

OBJECTIVE: To introduce the research progress on the relationship between gut microbiota dysbiosis and osteoarthritis (OA), focus on the possible mechanism of gut microbiota dysbiosis promoting OA, and propose a new therapeutic direction.

METHODS: The domestic and foreign research literature on the relationship between gut microbiota dysbiosis and OA was reviewed. The role of the former in the occurrence and development of OA and the new ideas for the treatment of OA were summarized.

RESULTS: The gut microbiota dysbiosis promotes the development of OA mainly in three aspects. First, the gut microbiota dysbiosis destroys intestinal permeability and causes low-grade inflammation, which aggravate OA. Secondly, the gut microbiota dysbiosis promotes the development of OA through metabolic syndrome. Thirdly, the gut microbiota dysbiosis is involved in the development of OA by regulating the metabolism and transport of trace elements. Studies have shown that improving gut microbiota dysbiosis by taking probiotics and transplanting fecal microbiota can reduce systemic inflammation and regulate metabolic balance, thus treating OA.

CONCLUSION: Gut microbiota dysbiosis is closely related to the development of OA, and improving gut microbiota dysbiosis can be an important idea for OA treatment.

RevDate: 2023-03-20

Br VK, SK Sarin (2023)

Acute -on- Chronic liver failure - Terminology, Mechanisms and Management.

Clinical and molecular hepatology pii:cmh.2022.0103 [Epub ahead of print].

Acute on chronic liver failure (ACLF) is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the "Golden Window" period of 7 days, give an opportunity for reversal of the syndrome. Scores like the APASL ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF C-ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade HE, and in the absence of > 2 organ failure or overt sepsis as there is a high chance of failure of conservative management and high mortality to improve survival of up to 80% at five years after liver transplantation. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation.

RevDate: 2023-03-21
CmpDate: 2023-03-21

Walter J, F Shanahan (2023)

Fecal microbiota-based treatment for recurrent Clostridioides difficile infection.

Cell, 186(6):1087.

Rebyota is a rectally administered fecal microbiota suspension for prevention of recurrence of Clostridioides difficile infection. The mechanism of action of Rebyota probably involves competitive exclusion of C. difficile by donor microbes with reduced toxin production; other factors may include restoration of protective taxa and modulation of the recipient's microbiome by phage, donor microbes, or metabolites.

RevDate: 2023-03-21
CmpDate: 2023-03-21

Hoshino E, Moriwaki K, Morimoto K, et al (2023)

Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.

The Journal of pediatrics, 253:101-106.e2.

OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting.

STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty.

RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening.

CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.

RevDate: 2023-03-20

Wynn AB, Beyer G, Richards M, et al (2023)

Procedure, Screening, and Cost of Fecal Microbiota Transplantation.

Cureus, 15(2):e35116.

Fecal microbiota transplantation (FMT) is currently considered a potential treatment for various GI-related illnesses, with the goal to replenish natural healthy flora of the GI tract that has been harmed because of antibiotic use or overgrowth of harmful bacteria. Current methods of administering the processed stool include colonoscopy and enema, while an oral capsule is being developed. Each method of administration carries its own set of risks, including adverse reactions to treatment, infection following the invasive administration procedure, and flare-ups of GI-related symptoms. Current oral administration through nasoduodenal tube poses a risk for aspiration which has not been ruled out as the cause of subsequent pneumonia and death in patient trials. The development of an oral capsule could address some of the faults of the current methods, not only making treatment more affordable and accessible but also less of a risk due to its minimally invasive nature. FMT is also a treatment option to attenuate adverse effects associated with antibiotic use, including combatting the emergence of antibiotic resistance, as well as adverse effects related to other medical treatments such as chemotherapy. While FMT is an unexplored treatment option for multiple gastrointestinal disorders and is currently still largely inaccessible for many patients financially, studies have suggested that it could be a more affordable treatment option long-term for patients as aspects of the treatment become more affordable with further research.

RevDate: 2023-03-20

Spartz EJ, Estafanos M, Mallick R, et al (2023)

Fecal Microbiota Transplantation for Fulminant Clostridioides Difficile Infection: A Combined Medical and Surgical Case Series.

Cureus, 15(2):e34998.

Urgent abdominal colectomy is indicated for patients with fulminant Clostridioides difficile infection (CDI) when other medical therapies fail, yet mortality remains high. Fecal microbiota transplant is a less invasive alternative approach for patients with fulminant CDI. We report the 30-day complications of patients with fulminant CDI who underwent either abdominal colectomy, fecal microbiota transplantation (FMT), or FMT followed by abdominal colectomy (FMT-CO). Methods: We performed a single-center, retrospective case review of combined medical and surgical patients with CDI at a large academic medical center between 2008 and 2016. Cohorts were identified as patients with fulminant CDI who underwent total abdominal colectomy alone (CO), FMT alone (FMT), or FMT-CO. We analyzed patient demographics, history, comorbidities, clinical and laboratory variables, CDI severity scores, and mortality outcomes at 30 days. Results: We identified 5,150 patients with CDI at our center during the review period; 16 patients met the criteria for fulminant CDI and were included in this study, with four patients in the CO cohort, eight patients in the FMT cohort, and four patients in the FMT-CO cohort. Demographics and CDI severity scores were similar for all three groups, although the selected comorbidity profiles differed significantly among the three cohorts. The 30-day mortality rates for patients in the CO, FMT, and FMT-CO groups were 25%, 12.5%, and 25%, respectively. Conclusions: FMT is an alternative or adjunctive therapy to colectomy for patients with fulminant CDI that is not associated with increased mortality. Implementation of FMT protocols in clinical practice would be dependent on the availability of qualified transplant material and successful early identification of patients likely to benefit from FMT.

RevDate: 2023-03-20

Zhang J, Zhu G, Wan L, et al (2023)

Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review.

Frontiers in psychiatry, 14:1123658.

BACKGROUND: Fecal microbiota transplantation (FMT) may be helpful in the treatment of autism spectrum disorder (ASD) as rebalancing the gut microbiome has been shown to potentially improve behavioral symptoms in children with ASD.

METHODS: This systematic review was conducted to assess the effect of FMT for children with ASD. The Embase, PubMed, Web of Science, and Cochrane Library databases were searched for articles published from inception to October 6, 2022. Two reviewers independently screened the identified records and undertook data extraction.

RESULTS: The search identified a total of five studies: two prospective open-label studies, two retrospective observational studies, and a case report; however, no randomized controlled trial was identified. All five studies reported a significant post-FMT-treatment improvement in neuropsychological assessment of ASD. The two prospective open-label studies suggested that the Autism Behavior Checklist (ABC) score, and the Social Responsiveness Scale (SRS) score at the posttreatment assessment decreased from the baseline (Wilcoxon signed-rank test; all p < 0.01]). The two retrospective observational studies suggested that FMT helped to improve the ASD symptoms. One observational study reported that the Childhood Autism Rating Scale (CARS) score and ABC score of the constipation group decreased from the baseline after the second course assessment (CARS [baseline: mean 35.25 ± standard deviation 4.36, second course: 32.5 ± 3.1, p = 0.015]; ABC [baseline: 56.21 ± 16.08, second course: 46.54 ± 16.54, p = 0.046]). Another observational study found that both ABC and CARS scores decreased as the number of FMT courses increased, and significant differences were found at the end of each course as compared with the baseline.

CONCLUSION: Compared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.

RevDate: 2023-03-20

Wang J, Liu X, Q Li (2023)

Interventional strategies for ischemic stroke based on the modulation of the gut microbiota.

Frontiers in neuroscience, 17:1158057.

The microbiota-gut-brain axis connects the brain and the gut in a bidirectional manner. The organism's homeostasis is disrupted during an ischemic stroke (IS). Cerebral ischemia affects the intestinal flora and microbiota metabolites. Microbiome dysbiosis, on the other hand, exacerbates the severity of IS outcomes by inducing systemic inflammation. Some studies have recently provided novel insights into the pathogenesis, efficacy, prognosis, and treatment-related adverse events of the gut microbiome in IS. In this review, we discussed the view that the gut microbiome is of clinical value in personalized therapeutic regimens for IS. Based on recent non-clinical and clinical studies on stroke, we discussed new therapeutic strategies that might be developed by modulating gut bacterial flora. These strategies include dietary intervention, fecal microbiota transplantation, probiotics, antibiotics, traditional Chinese medication, and gut-derived stem cell transplantation. Although the gut microbiota-targeted intervention is optimistic, some issues need to be addressed before clinical translation. These issues include a deeper understanding of the potential underlying mechanisms, conducting larger longitudinal cohort studies on the gut microbiome and host responses with multiple layers of data, developing standardized protocols for conducting and reporting clinical analyses, and performing a clinical assessment of multiple large-scale IS cohorts. In this review, we presented certain opportunities and challenges that might be considered for developing effective strategies by manipulating the gut microbiome to improve the treatment and prevention of ischemic stroke.

RevDate: 2023-03-20

DuPont HL, Suescun J, Jiang ZD, et al (2023)

Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study.

Frontiers in neurology, 14:1104759.

BACKGROUND AND PURPOSE: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease.

METHODS: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months).

RESULTS: Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group.

CONCLUSIONS: Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms.

CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, identifier: NCT03671785.

RevDate: 2023-03-20

Fourati S, Dumay A, Roy M, et al (2023)

Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach?.

Frontiers in cellular and infection microbiology, 13:1023441.

Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno-colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α- and β-diversity were significantly different from Sham. The FMT altered microbiota composition and α- and β-diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero-tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment.

RevDate: 2023-03-18

Berthouzoz E, Lazarevic V, Zekeridou A, et al (2023)

Oral and intestinal dysbiosis in Parkinson's disease.

Revue neurologique pii:S0035-3787(23)00876-7 [Epub ahead of print].

The suspicion of an origin of Parkinson's disease (PD) at the periphery of the body and the involvement of environmental risk factors in the pathogenesis of PD have directed the attention of the scientific community towards the microbiota. The microbiota represents all the microorganisms residing both in and on a host. It plays an essential role in the physiological functioning of the host. In this article, we review the dysbiosis repeatedly demonstrated in PD and how it influences PD symptoms. Dysbiosis is associated with both motor and non-motor PD symptoms. In animal models, dysbiosis only promotes symptoms in individuals genetically susceptible to Parkinson's disease, suggesting that dysbiosis is a risk factor but not a cause of Parkinson's disease. We also review how dysbiosis contributes to the pathophysiology of PD. Dysbiosis induces numerous and complex metabolic changes, resulting in increased intestinal permeability, local and systemic inflammation, production of bacterial amyloid proteins that promote α-synuclein aggregation, as well as a decrease in short-chain fatty acid-producing bacteria that have anti-inflammatory and neuroprotective potential. In addition, we review how dysbiosis decreases the efficacy of dopaminergic treatments. We then discuss the interest of dysbiosis analysis as a biomarker of Parkinson's disease. Finally, we give an overview of how interventions modulating the gut microbiota such as dietary interventions, pro-biotics, intestinal decontamination and fecal microbiota transplantation could influence the course of PD.

RevDate: 2023-03-17

Lin L, Zhang K, Xiong Q, et al (2023)

Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression.

Journal of autoimmunity pii:S0896-8411(23)00010-0 [Epub ahead of print].

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.

RevDate: 2023-03-17

Bellucci E, Chiereghin F, Pacifici F, et al (2023)

Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.

European review for medical and pharmacological sciences, 27(5):1921-1944.

The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.

RevDate: 2023-03-17

Bhatt A, Haslam A, V Prasad (2023)

The effect of gastrointestinal microbiome supplementation on immune checkpoint inhibitor immunotherapy: a systematic review.

Journal of cancer research and clinical oncology [Epub ahead of print].

PURPOSE: Gastrointestinal (GI) microbiome modulators, such as fecal microbiome transplants (FMTs), are being considered as supplements to standard immune checkpoint inhibitor (ICI) treatment to improve efficacy. This systematic review aims to assess the study design and outcomes of clinical trials that use FMTs to enhance ICI treatment.

METHODS: Systematic literature searches were conducted on PubMed and Embase using search terms that included names of ICIs and gastrointestinal microbiome. A first search identified interventional trials, and the second search identified interventional, retrospective, and observational studies.

RESULTS: The search for interventional trials produced 205 articles, 3 of which met the inclusion criteria. All studies had sample sizes ranging between 10 and 30 participants. 2 of the studies were single-arm studies with no control arm. One study reported an overall response rate (ORR) of 3 out of 15 (20%), a median progression-free survival (PFS) of 3 months, and a median overall survival (OS) of 7 months. The second study reported 1 complete response out of 10 (10%) and 2 partial responses out of 10 (20%). The third study reported an ORR of 58% vs. 20%, a median PFS of 12.7 months vs. 2.5 months in patients receiving nivolumab-ipilimumab plus CBM588 compared with patients receiving nivolumab-ipilimumab alone respectively, and an undefined median OS.

CONCLUSION: Current studies on the microbiome modulators with ICI use are limited in study design. Future clinical trials should be randomized, use larger sample sizes, and use an appropriate control arm to better ascertain the clinical effect of the GI microbiome on ICI treatment.

RevDate: 2023-03-17

Yi X, Huang C, Huang C, et al (2023)

Fecal microbiota from MRL/lpr mice exacerbates pristane-induced lupus.

Arthritis research & therapy, 25(1):42.

BACKGROUND: The roles of gut microbiota in the pathogenesis of SLE have been receiving much attention during recent years. However, it remains unknown how fecal microbiota transplantation (FMT) and microbial metabolites affect immune responses and lupus progression.

METHODS: We transferred fecal microbiota from MRL/lpr (Lpr) mice and MRL/Mpj (Mpj) mice or PBS to pristane-induced lupus mice and observed disease development. We also screened gut microbiota and metabolite spectrums of pristane-induced lupus mice with FMT via 16S rRNA sequencing, metagenomic sequencing, and metabolomics, followed by correlation analysis.

RESULTS: FMT from MRL/lpr mice promoted the pathogenesis of pristane-induced lupus and affected immune cell profiles in the intestine, particularly the plasma cells. The structure and composition of microbial communities in the gut of the FMT-Lpr mice were different from those of the FMT-Mpj mice and FMT-PBS mice. The abundances of specific microbes such as prevotella taxa were predominantly elevated in the gut microbiome of the FMT-Lpr mice, which were positively associated with functional pathways such as cyanoamino acid metabolism. Differential metabolites such as valine and L-isoleucine were identified with varied abundances among the three groups. The abundance alterations of the prevotella taxa may affect the phenotypic changes such as proteinuria levels in the pristane-induced lupus mice.

CONCLUSION: These findings further confirm that gut microbiota play an important role in the pathogenesis of lupus. Thus, altering the gut microbiome may provide a novel way to treat lupus.

RevDate: 2023-03-17

Shin YJ, Lee DY, Kim JY, et al (2023)

Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice.

Journal of ginseng research, 47(2):255-264.

BACKGROUND: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice.

METHODS: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests.

RESULTS: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF[+]NeuN[+] cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased.

CONCLUSION: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.

RevDate: 2023-03-16

Baldanzi G, Sayols-Baixeras S, Theorell-Haglöw J, et al (2023)

Obstructive sleep apnea was associated with the human gut microbiota composition and functional potential in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS).

Chest pii:S0012-3692(23)00352-5 [Epub ahead of print].

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.

RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?

STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.

RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.

INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.

RevDate: 2023-03-16

Jiang X, Liu Z, Ma Y, et al (2023)

Fecal microbiota transplantation affects the recovery of AD-skin lesions and enhances gut microbiota homeostasis.

International immunopharmacology, 118:110005 pii:S1567-5769(23)00326-0 [Epub ahead of print].

BACKGROUND: Accumulating evidence has shown that gut microbiota plays a key role in the progression of atopic dermatitis (AD). Fecal microbiota transplantation (FMT), as an effective method to restore gut microbiota homeostasis, has been successfully applied for treating many inflammatory diseases. However, the therapeutic effect of FMT on AD remains unclear. The following study examined the effect and mechanism of FMT on AD-skin lesions in an AD mouse model.

METHODS: In this study, we exposed the shaved back skin of BALB/c mice to calcipotriol (MC903) to induce AD model. Mice were then treated with FMT, which was performed with gut microbiota from healthy mice. The gut microbiota of treated mice was tracked by 16S rRNA gene sequencing. Mice skin tissues were examined by histopathology and inflammatory cytokines change in serum by ELISA.

RESULTS: FMT had a faster trend on the reversion of the increases in skin epidermal layer thicknesses and suppressed some of the representative inflammatory cytokines. The gut microbial community in the natural recovery process varied significantly in the FMT group at day 7 (ANOSIM P = 0.0229, r = 0.2593). Notably, FMT had a long-lasting and beneficial impact on the gut microbial compositions of AD mice by increasing the ratio of Firmicutes to Bacteroidetes and the amount of butyric-producing bacteria (BPB), including Erysipelotrichaceae, Lactobacillaceae, and Eubacteriacea. Furthermore, the relative abundances of gut microbiota-mediated functional pathways involved in the cell growth and death, amino acid, energy, lipid, and carbohydrate metabolisms, and immune system increased after FMT treatment.

CONCLUSION: FMT modulated the gut microbiota homeostasis and affected the recovery from AD-related inflammations, suggesting that it could be used as a treatment strategy for AD patients in the clinic.

RevDate: 2023-03-16

Shim JA, Ryu JH, Jo Y, et al (2023)

The role of gut microbiota in T cell immunity and immune mediated disorders.

International journal of biological sciences, 19(4):1178-1191.

Gut microbiota was only considered as a commensal organism that aids in digestion, but recent studies revealed that the microbiome play a critical role in both physiological and pathological immune system. The gut microbiome composition is altered by environmental factors such as diet and hygiene, and the alteration affects immune cells, especially T cells. Advanced genomic techniques in microbiome research defined that specific microbes regulate T cell responses and the pathogenesis of immune-mediated disorders. Here, we review features of specific microbes-T cell crosstalk and relationship between the microbes and immunopathogenesis of diseases including in cancers, autoimmune disorders and allergic inflammations. We also discuss the limitations of current experimental animal models, cutting-edge developments and current challenges to overcome in the field, and the possibility of considering gut microbiome in the development of new drug.

RevDate: 2023-03-16

Chen P, Wang K, Zhuang M, et al (2023)

An insight into gut microbiota and metabolites in the mice with adenomyosis.

Frontiers in cellular and infection microbiology, 13:1075387.

BACKGROUND: Adenomyosis (AM) is a benign uterine disease characterized pathologically by the invasion of endometrial tissue into the myometrium. The pathogenesis of AM is still far from clear. Although the gut microbiome and metabolomics are thought to contribute to a variety of diseases, the role of them in AM has not been revealed.

OBJECTIVE: To investigate changes in the gut microbiota and derived metabolites in AM mice.

METHOD: Female ICR mice were randomly assigned to AM and control groups, and pituitary transplantation was employed to perform AM modeling. Then, the fecal samples were obtained for microbial (16S rRNA gene sequencing) and metabolomic (liquid chromatography mass spectrometry, LC-MS) analysis.

RESULT: The results of gut microbiota analysis showed that the intestinal microbiota composition of AM mice was altered. The ratio of Firmicutes/Bacteroidetes and the relative abundance of Lactobacillus in AM group increased compared with the control group. Sixty differential expressed metabolites were identified in intestinal metabolites, mainly involved in steroid hormone biosynthesis, cysteine and methionine metabolism, and alanine, aspartate, and glutamate metabolism. Further, correlation analysis verified that L-methionine and L-cystine were negatively correlated with Bacteroides and positively correlated with Desulfovibrio. The Pregnenolone, Androsterone glucuronide, and Testosterone glucuronide were negatively correlated with Unidentified_Ruminococcaceae and Alistipes, whereas they positively correlated with Bacteroides.

CONCLUSION: AM mice have a unique gut microbiome and intestinal metabolites.

RevDate: 2023-03-15

Costa CJ, Cohen MW, Goldberg DC, et al (2023)

Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection.

Digestive diseases and sciences [Epub ahead of print].

BACKGROUND: Diabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.e., constipation) or decreased (i.e., diarrhea) total gastrointestinal transit times. These are recapitulated in the streptozocin-induced diabetic rat, which is a model of Type I Diabetes Mellitus.

AIMS: Examine the effects that a precursor of nicotinamide adenosine dinucleotide (NAD), nicotinamide riboside (NR), had on the development of dysmotility in induced diabetic rats and if fecal microbiota transplant (FMT) could produce the same results.

MATERIALS AND METHODS: Utilizing a 6-week treatment paradigm, NR was administered intraperitoneally every 48 h. Total gastrointestinal transit time was assessed weekly utilizing the carmine red method. Three weeks following hyperglycemic induction, FMT was performed between NR-treated animals and untreated animals.

SIGNIFICANT RESULTS: There is improvement in overall gastrointestinal transit time with the use of NR. 16S microbiome sequencing demonstrated decreased alpha and beta diversity in induced diabetic rats without change in animals receiving FMT. Improvements in myenteric plexus ganglia density in small and large intestines in diabetic animals treated with NR were seen.

CONCLUSIONS: NR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR's benefit as a treatment for diabetic enteric neuropathy. Streptozocin-induced diabetic rats have improved transit times and increased myenteric plexus ganglia density when treated with intraperitoneal nicotinamide riboside.

RevDate: 2023-03-16
CmpDate: 2023-03-16

Merenstein D, Pot B, Leyer G, et al (2023)

Emerging issues in probiotic safety: 2023 perspectives.

Gut microbes, 15(1):2185034.

Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related to probiotic use. The importance of whole genome sequencing, which enables determination of virulence, toxin, and antibiotic resistance genes, as well as clear assignment of species and strain identity, is emphasized. We present recommendations to guide the scientific and medical community on judging probiotic safety.

RevDate: 2023-03-15

Russell MW, Muste JC, Kuo BL, et al (2023)

Clinical trials targeting the gut-microbiome to effect ocular health: a systematic review.

Eye (London, England) [Epub ahead of print].

Clinical trials targeting the gut microbiome to mitigate ocular disease are now on the horizon. A review of clinical data thus far is essential to determine future directions in this novel promising field. This review examines recent clinical trials that support the plausibility of a gut-eye axis, and may form the basis of novel clinical interventions. PubMed was queried for English language clinical studies examining the relationships between gut microbiota and ocular pathology. 25 studies were extracted from 828 candidate publications, which suggest that gut imbalance is associated with ocular pathology. Of these, only four interventional studies exist which suggest probiotic supplementation or fecal microbiota transplant can reduce symptoms of chalazion or uveitis. The gut-eye axis appears to hold clinical relevance, but current data is limited in sample size and design. Further investigation via longitudinal clinical trials may be warranted.

RevDate: 2023-03-14

Kapoor B, Gulati M, Gupta R, et al (2023)

Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?.

Autoimmunity reviews pii:S1568-9972(23)00047-2 [Epub ahead of print].

Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.

RevDate: 2023-03-15

Aoi W, Inoue R, Mizushima K, et al (2023)

Exercise-acclimated microbiota improves skeletal muscle metabolism via circulating bile acid deconjugation.

iScience, 26(3):106251.

Habitual exercise alters the intestinal microbiota composition, which may mediate its systemic benefits. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet (HFD)-fed mice. Fecal samples from sedentary and exercise-trained mice were gavage-fed to germ-free mice. After receiving fecal samples from trained donor mice for 1 week, recipient mice had elevated levels of AMP-activated protein kinase (AMPK) and insulin growth factor-1 in skeletal muscle. In plasma, bile acid (BA) deconjugation was found to be promoted in recipients transplanted with feces from trained donor mice; free-form BAs also induced more AMPK signaling and glucose uptake than tauro-conjugated BAs. The transplantation of exercise-acclimated fecal microbiota improved glucose tolerance after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvements in mice by modifying circulating BAs. Our findings provide insights into the prevention and treatment of metabolic diseases.

RevDate: 2023-03-14

Rehman A, Tyree SM, Fehlbaum S, et al (2023)

A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: a randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults.

The Journal of nutrition, 153(1):96-105.

BACKGROUND: Natural products rich in polyphenols have been shown to lower plasma trimethylamine-n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota.

OBJECTIVES: We aimed to determine the impact of Fruitflow, a water-soluble tomato extract, on TMAO, fecal microbiota, and plasma and fecal metabolites.

METHODS: Overweight and obese adults (n = 22, BMI 28-35 kg/m[2]) were included in a double-blind, placebo-controlled, cross-over study receiving 2×150 mg Fruitflow per day or placebo (maltodextrin) for 4 wk with a 6-week wash-out between interventions. Stool, blood, and urine samples were collected to assess changes in plasma TMAO (primary outcome) as well as fecal microbiota, fecal and plasma metabolites, and urine TMAO (secondary outcomes). In a subgroup (n = 9), postprandial TMAO was evaluated following a choline-rich breakfast (∼450 mg). Statistical methods included paired t-tests or Wilcoxon signed rank tests and permutational multivariate analysis of variance.

RESULTS: Fruitflow, but not placebo, reduced fasting levels of plasma (-1.5 μM, P ≤ 0.05) and urine (-19.1 μM, P ≤ 0.01) TMAO as well as plasma lipopolysaccharides (-5.3 ng/mL, P ≤ 0.05) from baseline to the end of intervention. However, these changes were significant only for urine TMAO levels when comparing between the groups (P ≤ 0.05). Changes in microbial beta, but not alpha, diversity paralleled this with a significant difference in Jaccard distance-based Principal Component (P ≤ 0.05) as well as decreases in Bacteroides, Ruminococccus, and Hungatella and increases in Alistipes when comparing between and within groups (P ≤ 0.05, respectively). There were no between-group differences in SCFAs and bile acids (BAs) in both faces and plasma but several changes within groups such as an increase in fecal cholic acid or plasma pyruvate with Fruitflow (P ≤ 0.05, respectively). An untargeted metabolomic analysis revealed TMAO as the most discriminant plasma metabolite between groups (P ≤ 0.05).

CONCLUSIONS: Our results support earlier findings that polyphenol-rich extracts can lower plasma TMAO in overweight and obese adults related to gut microbiota modulation. This trial was registered at clinicaltrials.gov as NCT04160481 (https://clinicaltrials.gov/ct2/show/NCT04160481?term= Fruitflow&draw= 2&rank= 2).

RevDate: 2023-03-14
CmpDate: 2023-03-14

Wang L, Wei Z, Pan F, et al (2023)

Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis.

Frontiers in immunology, 14:1093233.

Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut-joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.

RevDate: 2023-03-13

Gholam-Mostafaei FS, Azimirad M, Naseri K, et al (2023)

Intestinal microbiota changes pre- and post-fecal microbiota transplantation for treatment of recurrent Clostridioides difficile infection among Iranian patients with concurrent inflammatory bowel disease.

Frontiers in microbiology, 14:1147945.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD.

METHODS: A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT.

RESULTS AND DISCUSSION: Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.

RevDate: 2023-03-13

van Lingen EE, Baunwall SSMD, Lieberknecht SSC, et al (2023)

Short- and long-term follow-up after fecal microbiota transplantation as treatment for recurrent Clostridioides difficile infection in patients with inflammatory bowel disease.

Therapeutic advances in gastroenterology, 16:17562848231156285.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity.

OBJECTIVES: We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD.

DESIGN: This is a multicentre cohort study conducted in five European FMT centres.

METHODS: Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death.

RESULTS: In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years).

CONCLUSION: FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.

RevDate: 2023-03-13

Zou B, Liu S, Li X, et al (2023)

Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn's disease.

Frontiers in cellular and infection microbiology, 13:1083236.

BACKGROUND: Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn's disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children.

METHODS: We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy.

RESULTS: Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029).

CONCLUSION: This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.

RevDate: 2023-03-11

Gao T, Feng M, Wang Z, et al (2023)

Microbiota-gut-adipose axis: butyrate-mediated the improvement effect on inflammatory response and fatty acid oxidation dysregulation attenuates obesity in sleep-restricted mice.

Microbes and infection pii:S1286-4579(23)00028-X [Epub ahead of print].

BACKGROUND: Insufficient sleep was considered as a substantial cause of obesity. The present study further explored the mechanism whereby sleep restriction (SR)-mediated intestinal dysbiosis induced metabolic disorder and ultimately lead to obesity in mice and the improvement effect of butyrate exerting on it.

METHODS: A continuous 3 months SR mouse model with or without butyrate supplementation and fecal microbiota transplantation to explore the key role of intestinal microbiota in butyrate improving inflammatory response in inguinal white adipose tissue (iWAT) and fatty acid oxidation dysfunction in brown adipose tissue (BAT), further ameliorating SR-induced obesity.

RESULTS: SR-mediated gut microbiota dysbiosis (down-regulation in butyrate level and up-regulation in LPS level) induced intestinal permeability increase and inflammatory response in iWAT and fatty acid oxidation dysfunction in BAT, ultimately resulting in obesity. Further, we demonstrated butyrate ameliorated gut microbiota homeostasis, suppressed inflammatory response via GPR43/LPS/TLR4/MyD88/GSK-3β/β-catenin loop in iWAT and restored fatty acid oxidation function via HDAC3/PPARα/PGC-1α/UCP1/Calpain1 pathway in BAT, ultimately reversing SR-induced obesity.

CONCLUSIONS: We revealed that gut dysbiosis is a key factor for SR-induced obesity and provided a better understanding of the effects of butyrate. We further expected that reversing SR-induced obesity by improving microbiota-gut-adipose axis disorder could be a possible treatment for metabolic diseases.

RevDate: 2023-03-11

Zhang CE, Yu XH, Cui YT, et al (2023)

Shengjiang Xiexin Decoction ameliorates antibiotic-associated diarrhea by altering the gut microbiota and intestinal metabolic homeostasis.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 113:154737 pii:S0944-7113(23)00095-8 [Epub ahead of print].

BACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD.

PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile.

METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT).

RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism.

CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.

RevDate: 2023-03-11

Yuan C, Fan J, Jiang L, et al (2023)

Integrated Analysis of Gut Microbiome and Liver Metabolome to Evaluate the Effects of Fecal Microbiota Transplantation on Lipopolysaccharide/D-galactosamine-Induced Acute Liver Injury in Mice.

Nutrients, 15(5): pii:nu15051149.

Acute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.

RevDate: 2023-03-11

Rodrigues T, Rodrigues Fialho S, Araújo JR, et al (2023)

Procedures in Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome: Systematic Review and Meta-Analysis.

Journal of clinical medicine, 12(5): pii:jcm12051725.

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis.

METHODS: A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms.

RESULTS: Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94-4.73; I[2] = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively).

CONCLUSION: Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed.

RevDate: 2023-03-11

Celiberto F, Losurdo G, Pricci M, et al (2023)

The State of the Art of Molecular Fecal Investigations for Helicobacter pylori (H. pylori) Antibiotic Resistances.

International journal of molecular sciences, 24(5): pii:ijms24054361.

A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of antibiotic resistance. However, the availability of sensitivity tests is not widespread and the guidelines have always indicated empirical treatments without taking into account the need to make sensitivity tests accessible, i.e., the necessary starting point for improving results in different geographical areas. Currently, the traditional tools for this purpose (culture) are based on performing an invasive investigation (endoscopy) and often involve technical difficulties; thus, they were only confined to the settings where multiple attempts at eradication have failed. In contrast, genotypic resistance testing of fecal samples using molecular biology methods is much less invasive and more acceptable to patients. The purpose of this review is to update the state of the art of molecular fecal susceptibility testing for the management of this infection and to extensively discuss the potential benefits of their large-scale deployment, i.e., novel pharmacological opportunities.

RevDate: 2023-03-11

Song L (2023)

Toward Understanding Microbial Ecology to Restore a Degraded Ecosystem.

International journal of environmental research and public health, 20(5): pii:ijerph20054647.

The microbial community plays an important role in maintaining human health, addressing climate change, maintaining environmental quality, etc. High-throughput sequencing leads to the discovery and identification of more microbial community composition and function in diverse ecosystems. Microbiome therapeutics such as fecal microbiota transplantation for human health and bioaugmentation for activated sludge restoration have drawn great attention. However, microbiome therapeutics cannot secure the success of microbiome transplantation. This paper begins with a view on fecal microbiota transplantation and bioaugmentation and is followed by a parallel analysis of these two microbial therapeutic strategies. Accordingly, the microbial ecology mechanisms behind them were discussed. Finally, future research on microbiota transplantation was proposed. Successful application of both microbial therapeutics for human disease and bioremediation for contaminated environments relies on a better understanding of the microbial "entangled bank" and microbial ecology of these environments.

RevDate: 2023-03-11

Jia X, He Y, Kang Z, et al (2023)

Comparison of Fecal Microbiota Communities between Primiparous and Multiparous Cows during Non-Pregnancy and Pregnancy.

Animals : an open access journal from MDPI, 13(5): pii:ani13050869.

Imbalances in the gut microbiota composition may lead to several reproductive disorders and diseases during pregnancy. This study investigates the fecal microbiome composition between primiparous and multiparous cows during non-pregnancy and pregnancy to analyze the host-microbial balance at different stages. The fecal samples obtained from six cows before their first pregnancy (BG), six cows during their first pregnancy (FT), six open cows with more than three lactations (DCNP), and six pregnant cows with more than three lactations (DCP) were subjected to 16S rRNA sequencing, and a differential analysis of the fecal microbiota composition was performed. The three most abundant phyla in fecal microbiota were Firmicutes (48.68%), Bacteroidetes (34.45%), and Euryarchaeota (15.42%). There are 11 genera with more than 1.0% abundance at the genus level. Both alpha diversity and beta diversity showed significant differences among the four groups (p < 0.05). Further, primiparous women were associated with a profound alteration of the fecal microbiota. The most representative taxa included Rikenellaceae_RC9_gut_group, Prevotellaceae_UCG_003, Christensenellaceae_R_7_group, Ruminococcaceae UCG-005, Ruminococcaceae UCG-013, Ruminococcaceae UCG-014, Methanobrevibacter, and [Eubacterium] coprostanoligenes group, which were associated with energy metabolism and inflammation. The findings indicate that host-microbial interactions promote adaptation to pregnancy and will benefit the development of probiotics or fecal transplantation for treating dysbiosis and preventing disease development during pregnancy.

RevDate: 2023-03-10

Clottes P, Benech N, Dumot C, et al (2023)

Gut microbiota and stroke: new avenues to improve prevention and outcome.

European journal of neurology [Epub ahead of print].

Despite major recent therapeutic advances, stroke remains a leading cause of disability and death. Consequently, new therapeutic targets need to be found to improve stroke outcome. The deleterious role of gut microbiota alteration (often mentioned as "dysbiosis") on cardiovascular diseases, including stroke and its risk factors, has been increasingly recognized. Gut microbiota metabolites, such as Trimethylamine-N-Oxyde (TMAO), Short Chain Fatty Acid (SCFA), and tryptophan, play a key role. Evidence of a link between alteration of the gut microbiota and cardiovascular risk factors exists, with a possible causality link supported by several pre-clinical studies. Gut microbiota alteration also seems to be implicated at the acute phase of stroke, with observational studies showing more non-neurological complications, higher infarct size and worse clinical outcome in stroke patients with altered microbiota. Microbiota targeted strategies have been developed, including prebiotics/probiotics, fecal microbiota transplantation, SCFA and TMAO inhibitors. Research teams have been using different time windows and endpoint for their studies, with various results. Considering the available evidence, we believe that studies focusing on microbiota targeted strategies in association with conventional stroke care should be conducted. Such strategies should be considered according to three therapeutic time windows: first, at the pre-stroke (primary prevention) or post-stroke (secondary prevention) phases, to enhance the control of cardiovascular risk factors. Secondly, at the acute phase of stroke, to limit the infarct size and the systemic complications and enhance the overall clinical outcome. Thirdly, at the subacute phase of stroke, to prevent stroke recurrence and promote neurological recovery.

RevDate: 2023-03-10

Zhang B, Fan X, Du H, et al (2023)

Foodborne Carbon Dot Exposure Induces Insulin Resistance through Gut Microbiota Dysbiosis and Damaged Intestinal Mucus Layer.

ACS nano [Epub ahead of print].

Foodborne carbon dots (CDs), an emerging food nanocontaminant, are an increasing risk factor for metabolic toxicity in mammals. Here, we report that chronic CD exposure induced glucose metabolism disorders via disruption of the gut-liver axis in mice. 16s rRNA analysis demonstrated that CD exposure decreased the abundance of beneficial bacteria (Bacteroides, Coprococcus, and S24-7) and increased the abundance of harmful bacteria (Proteobacteria, Oscillospira, Desulfovibrionaceae, and Ruminococcaceae), as well as increased the Firmicutes/Bacteroidetes ratio. Mechanistically, the increased pro-inflammatory bacteria release the endotoxin lipopolysaccharide, which induces an intestinal inflammation and disruption of the intestinal mucus layer, activating systemic inflammation and inducing hepatic insulin resistance in mice via the TLR4/NFκB/MAPK signaling pathway. Furthermore, these changes were almost completely reversed by probiotics. Fecal microbiota transplantation from CD-exposed mice induced glucose intolerance, damaged liver function, intestinal mucus layer injury, hepatic inflammation, and insulin resistance in the recipient mice. However, microbiota-depleted mice exposed to CDs had normal levels of these biomarkers consistent with microbiota-depleted control mice, which revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance. Together, our findings revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance and attempted to elucidate the specific underlying mechanism. Furthermore, we emphasized the importance of assessing the hazards associated with foodborne CDs.

RevDate: 2023-03-10

Zhao JW, Chang B, LX Sang (2023)

Fecal microbiota transplantation as potential first-line treatment for patients with Clostridioides difficile infection and prior appendectomy.

World journal of gastrointestinal surgery, 15(2):303-306.

Clostridioides difficile infection (CDI) is a global health problem. The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures, but there are still contradictions. In a retrospective study entitled "Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes" published in World J Gastrointest Surg 2021, the author found that prior appendectomy affects the severity of CDI. Appendectomy may be a risk factor for increasing the severity of CDI. Therefore, it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.

RevDate: 2023-03-10

Wang J, Zhang X, Li M, et al (2023)

Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection.

Therapeutics and clinical risk management, 19:207-217.

BACKGROUND: Antibody-mediated rejection (AMR) is emerging as the main cause of graft loss after kidney transplantation. Our previous study revealed the gut microbiota alternation associated with AMR in kidney transplant recipients, which was predicted to affect the metabolism-related pathways.

METHODS: To further investigate the shifts in intestinal metabolic profile among kidney transplantation recipients with AMR, fecal samples from kidney transplant recipients and patients with end-stage renal disease (ESRD) were subjected to untargeted LC-MS-based metabolomics.

RESULTS: A total of 86 individuals were enrolled in this study, including 30 kidney transplantation recipients with AMR, 35 kidney transplant recipients with stable renal function (KT-SRF), and 21 participants with ESRD. Fecal metabolome in patients with ESRD and kidney transplantation recipients with KT-SRF were parallelly detected as controls. Our results demonstrated that intestinal metabolic profile of patients with AMR differed significantly from those with ESRD. A total of 172 and 25 differential metabolites were identified in the KT-AMR group, when compared with the ESRD group and the KT-SRF group, respectively, and 14 were common to the pairwise comparisons, some of which had good discriminative ability for AMR. KEGG pathway enrichment analysis demonstrated that the different metabolites between the KT-AMR and ESRD groups or between KT-AMR and KT-SRF groups were significantly enriched in 33 or 36 signaling pathways, respectively.

CONCLUSION: From the metabolic point of view, our findings may provide key clues for developing effective diagnostic biomarkers and therapeutic targets for AMR after kidney transplantation.

RevDate: 2023-03-09

Yang J, Wang L, Mei M, et al (2023)

Electroacupuncture repairs intestinal barrier by upregulating CB1 through gut microbiota in DSS-induced acute colitis.

Chinese medicine, 18(1):24.

BACKGROUND: A few studies have reported that electroacupuncture (EA) can repair the intestinal barrier through unknown mechanisms. Cannabinoid receptor 1 (CB1) was shown to play an important role in the protection of the gut barrier in recent studies. Gut microbiota can influence the expression of CB1. In this study, we explored the effect of EA on the gut barrier in acute colitis and its mechanism.

METHODS: A dextran sulfate sodium (DSS)-induced acute colitis model, CB1 antagonist model and fecal microbiota transplantation (FMT) model were used in this study. The disease activity index (DAI) score, colon length, histological score, and inflammatory factors were detected to evaluate colonic inflammation. Methods for detecting intestinal barrier functions included the expression of tight junction proteins, intestinal permeability, and the number of goblet cells. Moreover, 16S rRNA sequencing was applied to analyze alterations in the gut microbiota. Western blotting and RT-PCR were performed to assess the levels of CB1 and autophagy-related proteins. Autophagosomes were observed by transmission electron microscopy.

RESULTS: EA reduced the DAI score, histological score, levels of inflammatory factors, and restored the colon length. Moreover, EA increased the expression of tight junction proteins and the number of goblet cells, and decreased intestinal permeability. In addition, EA remodeled the community structure of the gut microbiota, increased the expression of CB1, and enhanced the degree of autophagy. However, the therapeutic effects were reversed by CB1 antagonists. In addition, FMT in the EA group exhibited similar effects to EA and upregulated CB1.

CONCLUSIONS: We concluded that EA may protect intestinal barrier functions by increasing the expression of CB1 to enhance autophagy through gut microbiota in DSS-induced acute colitis.

RevDate: 2023-03-09

Yang T, Guan Q, Shi JS, et al (2023)

Metformin alleviates liver fibrosis in mice by enriching Lactobacillus sp. MF-1 in the gut microbiota.

Biochimica et biophysica acta. Molecular basis of disease, 1869(5):166664 pii:S0925-4439(23)00030-3 [Epub ahead of print].

BACKGROUND: Liver fibrosis is associated with gut dysbiosis. Metformin administration has emerged as a promising method for the treatment of organ fibrosis. We aimed to investigate whether metformin ameliorates liver fibrosis by enhancing the gut microbiota in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and the underlying mechanism.

MATERIALS AND METHODS: A liver fibrosis mouse model was established, and the therapeutic effects of metformin were observed. We administered antibiotic treatment and performed fecal microbiota transplantation (FMT), and 16S rRNA-based microbiome analysis to evaluate the effects of the gut microbiome on metformin-treated liver fibrosis. We isolated the bacterial strain preferably enriched by metformin and assessed its antifibrotic effects.

RESULTS: Metformin treatment repaired the gut integrity of the CCl4-treated mice. It reduced the number of bacteria in colon tissues and reduced the portal vein lipopolysaccharide (LPS) levels. The FMT performed on the metformin-treated CCl4 mice alleviated their liver fibrosis and reduced their portal vein LPS levels. The markedly changed gut microbiota was screened out from the feces and named Lactobacillus sp. MF-1 (L. sp. MF-1). In the CCl4-treated mice, daily gavage of L. sp. MF-1 maintained gut integrity, inhibited bacterial translocation, and reduced liver fibrosis. Mechanistically, metformin or L. sp. MF-1 inhibited the apoptosis of intestinal epithelial cells and restored CD3[+] intestinal intraepithelial lymphocytes in the ileum and CD4[+]Foxp3[+] lamina propria lymphocytes in the colon.

CONCLUSIONS: Metformin and its enriched L. sp. MF-1 can reinforce the intestinal barrier to alleviate liver fibrosis by restoring immune function.

RevDate: 2023-03-09

Trinh S, Keller L, Herpertz-Dahlmann B, et al (2023)

[Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders].

Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie [Epub ahead of print].

Fecal Microbiota Transplants in the Context of (Child and Adolescent) Psychiatric Disorders Abstract: There has recently been a significant increase in interest in gut microbiota and its interaction with the brain (gut-brain axis). Not only are the findings of microbiome research interesting for basic scientists, they also offer relevant insights for clinical practice. A causal relationship between gut microbiome and various somatic diseases such as diabetes mellitus, inflammatory bowel diseases, and obesity as well as psychiatric diseases such as major depression, anxiety disorders, and eating disorders seems plausible. To study the causal relationship of intestinal bacteria with individual phenotypes, researchers apply so-called stool transplantations (fecal microbiota transplantations) in the preclinical context. For this purpose, they transfer microbiota samples from patients into laboratory animals to observe possible changes in phenotype. In the clinical context, fecal microbiota transplantation is already being used with therapeutic intentions for selected diseases, for example, recurrent infections with Clostridioides difficile or inflammatory bowel diseases; they have already become part of the official clinical guidelines for C. difficile. For many other diseases, however, including mental illnesses, the potential of using fecal transplantations for therapeutic purposes is still being explored. Previous findings suggest that the intestinal microbiome, particularly fecal microbiota transplantations, represent a promising starting point for new therapeutic approaches.

RevDate: 2023-03-09

He J, Yang M, Quan X, et al (2023)

Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.

International journal of urology : official journal of the Japanese Urological Association [Epub ahead of print].

OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM.

METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized.

RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites.

CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.

RevDate: 2023-03-09

Gao P, Liu L, Zhang Z, et al (2023)

Abdominal catheter-induced intussusception following renal transplantation in two pediatric recipients: 2 cases report and literature review.

Translational pediatrics, 12(2):280-286.

BACKGROUND: Intussusception is a frequent abdominal emergency in the pediatric population when the proximal bowel invaginates into the distal bowel. However, catheter-induced intussusception has not previously been described in pediatric renal transplant recipients, and the risk factors need to be investigated.

CASE DESCRIPTION: We report 2 cases of post-transplant intussusception which were caused by abdominal catheters. Case 1 experienced ileocolonic intussusception 3 months after renal transplantation and presented with intermittent abdominal pain; the intussusception was successfully managed using air enema. However, this child experienced a total of 3 episodes of intussusception within 4 days, which discontinued only after removal of the peritoneal dialysis catheter. No further intussusception recurrence was observed and the patient's intermittent pain disappeared during the follow-up. Case 2 developed ileocolonic intussusception 2 days after renal transplantation and presented currant jelly stools. The intussusception was completely irreducible until the intraperitoneal drainage catheter was eliminated; the patient discharged normal feces during the following days. A search in the databases of PubMed, Web of Science, and Embase yielded 8 similar cases. Our 2 cases had a younger age at disease onset than those retrieved in the search, and abdominal catheter was revealed as a lead point. Possible leading points of the 8 previously reported cases included post-transplant lymphoproliferative disorder (PTLD), acute appendicitis, tuberculosis, lymphocele, and firm adhesions. We noted that our cases were managed successfully with nonoperative treatment, whereas the 8 reported cases underwent surgical intervention. All of the 10 cases of intussusception occurred after renal transplantation and showed that intussusception had been induced by a lead point.

CONCLUSIONS: Our 2 cases implied that abdominal catheter could be a lead point to induce intussusception, especially in pediatric recipients with abdominal disorder. This experience may be applicable to other surgeries involving indwelling abdominal catheters in children. Health practitioners should consider this pathologic lead point and avoid serious consequences when intussusception occurs.

RevDate: 2023-03-09

Liu X, Tang H, Zhou Q, et al (2023)

Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events.

Frontiers in immunology, 14:1109281.

INTRODUCTION: The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established.

METHODS: From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs.

RESULTS: Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (P=0.003). Bifidobacterium, Faecalibacterium, and Agathobacter were less abundant and Erysipelatoclostridium more abundant in irAE patients, while Bacteroides and Bifidobacterium were less abundant and Enterococcus more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (P=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9).

CONCLUSIONS: The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.

RevDate: 2023-03-08

Wu D, Zhang C, Liu Y, et al (2023)

Beyond faecal microbiota transplantation, the non-negligible role of faecal virome or bacteriophage transplantation.

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi pii:S1684-1182(23)00042-7 [Epub ahead of print].

Intestinal microbiota, which contains bacteria, archaea, fungi, protists, and viruses including bacteriophages, is symbiotic and evolves together with humans. The balanced intestinal microbiota plays indispensable roles in maintaining and regulating host metabolism and health. Dysbiosis has been associated with not only intestinal diseases but other diseases such as neurology disorders and cancers. Faecal microbiota transplantation (FMT) or faecal virome or bacteriophage transplantation (FVT or FBT), transfers faecal bacteria or viruses, with a focus on bacteriophage, from one healthy individual to another individual (normally unhealthy condition), and aims to restore the balanced gut microbiota and assist in subduing diseases. In this review, we summarized the applications of FMT and FVT in clinical settings, discussed the advantages and challenges of FMT and FVT currently and proposed several considerations prospectively. We further provided our understanding of why FMT and FVT have their limitations and raised the possible future development strategy of FMT and FVT.

RevDate: 2023-03-09

Kumei S, Ishioh M, Nozu T, et al (2023)

Prostaglandin I2 suppresses the development of gut-brain axis disorder in irritable bowel syndrome in rats.

Biochimica et biophysica acta. General subjects, 1867(5):130344 pii:S0304-4165(23)00042-9 [Epub ahead of print].

In this study, we attempted to clarify a role of prostaglandin (PG) I2 and its specific receptor, IP in the pathogenesis of irritable bowel syndrome (IBS) using a maternal separation (MS)-induced IBS model. Administration of beraprost (BPS), a specific IP agonist, improved visceral hypersensitivity and depressive state with decreased serum CRF level in the IBS rats. To clarify the mechanism of the effect of BPS, we performed serum metabolome analysis and 1-methylnicotinamide (1-MNA) was identified as a possible candidate for a clue metabolite of pathogenesis of IBS. The serum 1-MNA levels revealed inverse correlation to the level of visceral sensitivity, and positive correlation to a depression marker, immobilizing time. Administration of 1-MNA induced visceral hypersensitivity and depression with increased levels of serum CRF. Since fecal 1-MNA is known for a marker of dysbiosis, we examined the composition of fecal microbiota by T-RFLP analysis. The proportion of clostridium cluster XI, XIVa and XVIII was significantly changed in MS-induced IBS rats treated with BPS. Fecal microbiota transplant of BPS-treated rats improved visceral hypersensitivity and depression in IBS rats. These results suggest for the first time that PGI2-IP signaling plays an important role in IBS phenotypes such as visceral hypersensitivity and depressive state. BPS modified microbiota, thereby inhibition of 1-MNA-CRF pathway, followed by improvement of MS-induced IBS phenotype. These results suggest that the PGI2-IP signaling could be considered to be a therapeutic option for IBS.

RevDate: 2023-03-08

Wu Y, Zheng Y, Wang X, et al (2023)

Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity.

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

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia-Shigella, which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.

RevDate: 2023-03-07

Zhou S, Cui Y, Zhang Y, et al (2023)

Fecal microbiota transplantation for induction of remission in Crohn's disease: a systematic review and meta-analysis.

International journal of colorectal disease, 38(1):62.

PURPOSE: Fecal microbiota transplantation (FMT) has been found to be a potential treatment for Crohn's disease (CD). We sought to perform a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD.

METHODS: Electronic databases were searched for studies until January 2023. Clinical remission was established as the primary outcome. The secondary outcome was clinical response, endoscopic remission, minor adverse events, serious adverse events, and changes in disease activity indices, biochemical indicators, and microbial diversities. Pooled effect sizes and 95% confidence intervals (CIs) were calculated under the random effects model.

RESULTS: Eleven cohort studies and one randomized controlled trial involving 228 patients were included. In a meta-analysis, the pooled proportion of adult patients with active CD that achieved clinical remission 2 to 4 weeks after FMT was 57% (95% CI = 49-64%) with a low risk of heterogeneity (I[2] = 37%). Furthermore, our results showed that FMT significantly (standardized mean difference = -0.66; 95% CI = -1.12 to -0.20; I[2] = 0) reduced Crohn's disease activity index scores 4 to 8 weeks after FMT. Subgroup analyses showed no difference between FMT methodologies, except for pre-FMT treatment with antibiotics (P = 0.02). Most adverse events were self-limiting and disappeared spontaneously within hours or days after FMT. Microbiota analysis showed an increased Shannon diversity and a shift toward donor-like microbiome after FMT.

CONCLUSION: FMT could be a promising therapy in the short-term treatment of active CD. More placebo-controlled randomized trials with a long-term follow-up treatment are necessary.

TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322694 No. CRD42022322694.

RevDate: 2023-03-07

Körner E, A Lorentz (2023)

Fecal microbiota transplantation in patients with irritable bowel syndrome: an overview of current studies.

Journal of applied microbiology pii:7071894 [Epub ahead of print].

As dysbiosis is a key factor associated with irritable bowel syndrome (IBS), modulation of the intestinal microbiota could improve IBS symptoms and quality of life. Fecal microbiota transplantation (FMT) could be one efficient way to restore bacterial composition in IBS patients. This review comprises 12 clinical trials published from 2017 to 2021. Inclusion criteria were the assessment of IBS symptoms using the IBS symptom severity score (IBS-SSS), quality of life measured by the lBS quality of life scale (IBS-QOL) and gut microbiota analysis. Improved symptoms were reported in all 12 studies, paralleling with an increased quality of life after FMT, but also partly after placebo treatment. The use of oral capsules showed that the placebo treatment can have similar or even stronger positive effects on IBS patients than FMT. Gastroscopic FMT appears to link modulation of the gut microbiome to significant symptom reduction in patients. The patient's microbiota profile shifted towards their respective donors. Symptom worsening or decreased quality of life after FMT was not reported. The results show, that FMT could be a therapeutic approach in IBS patients. Further research is needed to investigate whether FMT has a more beneficial effect on IBS patient than placebo treatment with the patient's own stool, placebo capsules or bowel cleansing. Moreover, optimal donor selection, frequency, dosage and route of delivery still need to be defined.

RevDate: 2023-03-08
CmpDate: 2023-03-08

Chopra T (2023)

A profile of the live biotherapeutic product RBX2660 and its role in preventing recurrent Clostridioides difficile infection.

Expert review of anti-infective therapy, 21(3):243-253.

INTRODUCTION: Clostridiodes difficile infection (CDI) is a life-threatening illness that has been labelled as an urgent threat by the Centers for Disease prevention (CDC).

AREAS COVERED: RBX2660, a live biotherapeutic product offers a very promising treatment option for patients with recurrent Clostridiodes difficile infection(rCDI). RBX2660 restores the healthy gut microbiome and shows clinically meaningful benefits for patients suffering from rCDI. Safety, efficacy, and tolerability of RBX2660 have been thoroughly assessed .

EXPERT OPINION: An FDA-approved, standardized, and accessible microbiota restoration product like RBX2660 would provide a new option for patients in need of treatment for rCDI by breaking the cycle of disease recurrence.

RevDate: 2023-03-07

Daoust L, Choi BS, Agrinier AL, et al (2022)

Gnotobiotic mice housing conditions critically influence the phenotype associated with transfer of faecal microbiota in a context of obesity.

Gut pii:gutjnl-2021-326475 [Epub ahead of print].

OBJECTIVE: Faecal microbiota transplantation (FMT) in germ-free (GF) mice is a common approach to study the causal role of the gut microbiota in metabolic diseases. Lack of consideration of housing conditions post-FMT may contribute to study heterogeneity. We compared the impact of two housing strategies on the metabolic outcomes of GF mice colonised by gut microbiota from mice treated with a known gut modulator (cranberry proanthocyanidins (PAC)) or vehicle.

DESIGN: High-fat high-sucrose diet-fed GF mice underwent FMT-PAC colonisation in sterile individual positive flow ventilated cages under rigorous housing conditions and then maintained for 8 weeks either in the gnotobiotic-axenic sector or in the specific pathogen free (SPF) sector of the same animal facility.

RESULTS: Unexpectedly, 8 weeks after colonisation, we observed opposing liver phenotypes dependent on the housing environment of mice. Mice housed in the GF sector receiving the PAC gut microbiota showed a significant decrease in liver weight and hepatic triglyceride accumulation compared with control group. Conversely, exacerbated liver steatosis was observed in the FMT-PAC mice housed in the SPF sector. These phenotypic differences were associated with housing-specific profiles of colonising bacterial in the gut and of faecal metabolites.

CONCLUSION: These results suggest that the housing environment in which gnotobiotic mice are maintained post-FMT strongly influences gut microbiota composition and function and can lead to distinctive phenotypes in recipient mice. Better standardisation of FMT experiments is needed to ensure reproducible and translatable results.

RevDate: 2023-03-07

Kundu S, Nayak S, Rakshit D, et al (2023)

The microbiome-gut-brain axis in Epilepsy: Pharmacotherapeutic target from bench evidence for potential bedside applications.

European journal of neurology [Epub ahead of print].

Gut-brain axis confers to the bidirectional intimation between the gut and brain and modulates gut homeostasis and central nervous system through the hypothalamic-pituitary-adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. The preclinical and clinical report showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy. Advanced consideration of the gut-microbiota-brain axis can reduce ambiguity about epilepsy pathology, antiepileptic drugs, and effective therapeutic targets. Gut microbiota sequencing analysis reported that the level of Proteobacteria, Verrucomicrobia, Fusobacteria, and Firmicutes was increased, and the level of Actinobacteria and Bacteroidetes was decreased in the epilepsy patients. The clinical and preclinical studies have also indicated that probiotics, ketogenic diet, faecal microbiota transplantation and antibiotic can improve gut dysbiosis and alleviate seizure by enhancing the abundance of healthy biota. This study aims to give an overview of the connection between gut microbiota and epilepsy, how gut microbiome changes may cause epilepsy, and whether gut microbiome restoration could be used as a treatment for epilepsy.

RevDate: 2023-03-07

Liu J, Liu H, Teng Y, et al (2023)

A high-sucrose diet causes microbiota composition shift and promotes the susceptibility of mice to Salmonella Typhimurium infection.

Food & function [Epub ahead of print].

A westernized diet characterized by high fat and sugar is tightly associated with the development of metabolic diseases and inflammatory bowel disease. Although a high-fat diet has been extensively studied for its involvement in various diseases, fewer studies have examined the impact of a high-sugar diet on the development of certain diseases, particularly enteric infections. This study aimed to explore the effect of a high sucrose diet on Salmonella Typhimurium-induced infection. C57BL/6 mice received a normal diet (Control) or a high sucrose diet (HSD) for eight weeks and then were infected by Salmonella Typhimurium. The high-sugar diet profoundly altered the relative abundance of certain microbial taxa. Bacteroidetes and Verrucomicrobiota were more abundant in normal diet-fed mice than in HSD-fed mice. Moreover, short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were significantly higher in mice from the control group than the HSD group. More S. Typhimurium counts in feces and other tissues were observed in HSD-fed mice after infection. Tight junction proteins and antimicrobial peptides were significantly decreased in HSD-fed mice. Fecal microbiota transplantation (FMT) demonstrated that mice that received normal fecal microbiota had lower Salmonella Typhimurium burdens compared with mice that received HSD fecal microbiota, indicating that the altered microbial communities are associated with the severity of infection. Together, these findings suggest that the excessive intake of sucrose disturbs intestinal homeostasis and predisposes mice to Salmonella-induced infection.

RevDate: 2023-03-06

Renteria K, Nguyen H, GY Koh (2023)

The role of vitamin D in depression and anxiety disorders: a review of the literature.

Nutritional neuroscience [Epub ahead of print].

BACKGROUND: Prevalence of mental health disorders continue to increase worldwide. Over the past decades, suboptimal vitamin D (VD) levels and gut dysbiosis have been associated with neurological dysfunction and psychiatric disorders.

METHODS: In this review, we examined the available literature on VD and mental health disorders, particularly depression and anxiety, in both clinical and pre-clinical studies.

RESULTS: Our extensive review failed to find a link between VD deficiency, depression, and anxiety-related behavior in preclinical animal models. However, strong evidence suggests that VD supplementation may alleviate symptoms in chronically stressed rodents, with some promising evidence from clinical studies. Further, fecal microbiota transplantations suggest a potential role of gut microbiota in neuropsychiatric disorders, although the underlying mechanisms remain to be fully elucidated. It has been postulated that serotonin, primarily produced by gut bacteria, may be a crucial factor. Hence, whether VD has the ability to impact gut microbiota and modulate serotonin synthesis warrants further investigation.

CONCLUSIONS: Taken together, literature has suggested that VD may serve as a key regulator in the gut-brain axis to modulate gut microbiota and alleviate symptoms of depression and anxiety. The inconsistent results of VD supplementation in clinical studies, particularly among VD deficient participants, suggests that current intake recommendations may need to be re-evaluated for individuals at-risk (i.e. prior to diagnosis) of developing depression and/or anxiety.

RevDate: 2023-03-07
CmpDate: 2023-03-07

Ballif A (2023)

[Not Available].

Revue medicale suisse, 19(816):434.

RevDate: 2023-03-07
CmpDate: 2023-03-07

Brenig A, Broekaert I, Gerner P, et al (2023)

Microbiome analysis and fecal microbiota transfer in pediatric gastroenterology - a structured online survey in German-speaking countries.

International journal of colorectal disease, 38(1):59.

PURPOSE: To assess the current attitude and the status quo towards the use of microbiome analysis and fecal microbiota transfer (FMT) in pediatric patients in German-speaking pediatric gastroenterology centers.

METHODS: A structured online survey among all certified facilities of the German-speaking society of pediatric gastroenterology and nutrition (GPGE) was conducted from November 01, 2020, until March 30, 2021.

RESULTS: A total of 71 centers were included in the analysis. Twenty-two centers (31.0%) use diagnostic microbiome analysis, but only a few perform analysis frequently (2; 2.8%) or regularly (1; 1.4%). Eleven centers (15.5%) have performed FMT as a therapeutic approach. Most of these centers use individual in-house donor screening programs (61.5%). One-third (33.8%) of centers rate the therapeutic impact of FMT as high or moderate. More than two-thirds (69.0%) of all participants are willing to participate in studies assessing the therapeutic effect of FMT.

CONCLUSIONS: Guidelines for microbiome analyses and FMT in pediatric patients and clinical studies investigating their benefits are absolutely necessary to improve the patient-centered care in pediatric gastroenterology. The long-term and successful establishment of pediatric FMT centers with standardized procedures for patient selection, donor screening, application route, volume, and frequency of use is highly required to obtain a safe therapy.

RevDate: 2023-03-07
CmpDate: 2023-03-07

Teng T, Sun G, Song X, et al (2023)

The early faecal microbiota transfer alters bile acid circulation and amino acid transport of the small intestine in piglets.

Journal of animal physiology and animal nutrition, 107(2):564-573.

The purpose of this study was to investigate the effects of faecal microbiota transfer (FMT) with lactation Min sows as faecal donor on blood immunity, small intestine amino acid transport capacity, bile acid circulation, and colon microbiota of recipient piglets. From Days 1 to 10, the recipient group (R group) was orally inoculated with a faecal suspension. The control group (Con group) was orally inoculated with sterile physiological saline. On Day 21, the results showed that the immunoglobulin A (IgA) concentration in plasma of the R group was increased (p < 0.05). The expression of 4F2hc in the jejunal mucosa and ileum mucosa of the R group was ameliorated (p < 0.05). The relative abundance of Synergistetes in the colon of the R group was increased, Proteobacteria was diminished by FMT (p < 0.05). On Day 40, the concentrations of IgA, IgG, and interleukin-2 detected in the plasma of the R group were increased (p < 0.05). FXR and fibroblast growth factor 19 gene expression was upregulated in ileum mucosa, CYP7A1 and Na[+] taurocholate cotransporter polypeptide gene expression were downregulated in the liver and organic solute transporters α/β was downregulated in colonic mucosa (p < 0.05). The relative abundance of Proteobacteria and Spirochaetes in the colon of the R group was decreased (p < 0.05). In conclusion, an early FMT with lactation Min sows as faecal donors can alter the small intestine amino acid transport capacity, bile acid circulation, and colonic microbiota of recipient piglets during lactation and after weaning.

RevDate: 2023-03-06

Takimoto Y, Chu PS, Nakamoto N, et al (2023)

Myeloid TLR4 signaling promotes post-injury withdrawal resolution of murine liver fibrosis.

iScience, 26(3):106220.

The fate of resolution of liver fibrosis after withdrawal of liver injury is still incompletely elucidated. Toll-like receptor 4 (TLR4) in tissue fibroblasts is pro-fibrogenic. After withdrawal of liver injury, we unexpectedly observed a significant delay of fibrosis resolution as TLR4 signaling was pharmacologically inhibited in vivo in two murine models. Single-cell transcriptome analysis of hepatic CD11b[+] cells, main producers of matrix metalloproteinases (MMPs), revealed a prominent cluster of restorative Tlr4-expressing Ly6c2-low myeloid cells. Delayed resolution after gut sterilization suggested its microbiome-dependent nature. Enrichment of a metabolic pathway linking to a significant increase of bile salt hydrolase-possessing family Erysipelotrichaceae during resolution. Farnesoid X receptor-stimulating secondary bile acids including 7-oxo-lithocholic acids upregulated MMP12 and TLR4 in myeloid cells in vitro. Fecal material transplant in germ-free mice confirmed phenotypical correlations in vivo. These findings highlight a pro-fibrolytic role of myeloid TLR4 signaling after injury withdrawal and may provide targets for anti-fibrotic therapy.

RevDate: 2023-03-06

Maestri M, Santopaolo F, Pompili M, et al (2023)

Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies.

Frontiers in nutrition, 10:1110536.

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.

RevDate: 2023-03-06

Matošević M, Kos I, Davidović M, et al (2023)

Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature.

Frontiers in pediatrics, 11:1092860.

INTRODUCTION: As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality.

CASE REPORT: We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19. His condition quickly deteriorated and he developed oliguria, accompanied with diarrhea, vomiting and oral intake intolerance. HUS was suspected, supported with compelling laboratory findings, including decreased platelets count and C3 levels, elevated LDH, urea, serum creatinine and sC5b-9 and presence of schistocytes in peripheral blood, negative fecal Shiga toxin and normal ADAMTS13 metalloprotease activity. The patient was given C5 complement blocker Ravulizumab and started to display rapid improvement.

CONCLUSION: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.

RevDate: 2023-03-02

Liu Y, Ji X, Huang Y, et al (2023)

Older patients benefit more from sequential courses of washed microbiota transplantation than younger population with ulcerative colitis.

Scandinavian journal of gastroenterology [Epub ahead of print].

OBJECTIVES: The short-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) has increasingly been evaluated. However, few studies have examined the long-term efficacy and its predictors. This study aimed to assess the clinical factors affecting the long-term efficacy of FMT for patients with UC.

METHODS: This is a retrospective analysis of a prospective trial (NCT01790061) for patients with UC undergoing washed microbiota transplantation (WMT), which is the improved methodology of FMT. The long-term clinical efficacy of WMT and the factors affecting efficacy were analyzed.

RESULTS: A total of 259 patients were included for analysis. Of 70.7% (183/259) of patients achieved a clinical response at 1 month after WMT and 29.7% (77/259) achieved steroid-free clinical remission 6 months after WMT. Total 44 patients maintained a clinical response for ≥24 months, and 33 (17.1%, 33/193) achieved steroid-free clinical remission for ≥24 months with WMT monotherapy. Patients with age at UC onset of ≥60 years, mild disease severity and undergoing ≥2 courses of WMT during the response within 6 months were more likely to achieve steroid-free clinical remission 6 months after WMT. Besides, independent factors associated with the long-term response of WMT for UC were age at onset of ≥60 years and ≥2 courses of WMT during the response.

CONCLUSIONS: This study indicated WMT could induce short-term steroid-free clinical remission and maintain long-term response in UC, especially for older patients and patients undergoing sequential courses.

RevDate: 2023-03-02

Spreafico A, Heirali AA, Araujo DV, et al (2023)

First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO Trial).

Annals of oncology : official journal of the European Society for Medical Oncology pii:S0923-7534(23)00088-1 [Epub ahead of print].

BACKGROUND: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICI) in humans, and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use.

PATIENTS AND METHODS: We conducted an early phase clinical trial of a cultivated, orally-delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic-4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors.

RESULTS: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes, however, differences in MET4-species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids.

CONCLUSIONS: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.

RevDate: 2023-03-02

Lian Z, Xu Y, Wang C, et al (2023)

Gut microbiota-derived melatonin from Puerariae Lobatae Radix-resistant starch supplementation attenuates ischemic stroke injury via a positive microbial co-occurrence pattern.

Pharmacological research pii:S1043-6618(23)00070-1 [Epub ahead of print].

Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic; however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter, Bacteroidales_S24-7_group, Prevotella_9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke.

RevDate: 2023-03-02

Grover S (2023)

Continuing Medical Education Questions: March 2023.

The American journal of gastroenterology, 118(3):404.

Article Title: Fecal Microbiota Transplantation Across the Lifespan- Balancing Efficacy, Safety, and Innovation.

RevDate: 2023-03-01

Zhang Y, Peng Y, X Xia (2023)

Autoimmune diseases and gut microbiota: a bibliometric and visual analysis from 2004 to 2022.

Clinical and experimental medicine [Epub ahead of print].

Many studies have shown that gut microbiota is closely related to autoimmune diseases (ADs). Studies on gut microbiota and ADs have also increased significantly, but no bibliometric analysis has summarized the association between gut microbiota and ADs. This study aimed to conduct a bibliometric and visual analysis of published studies on gut microbiota and ADs. Based on the Web of Science Core Collection SCI-expanded database, we utilize Excel 2019 and visualization analysis tools VOSviewer and co-occurrence13.2 (COOC13.2) for analysis. A total of 2516 related kinds of literature were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, and the author is Mikael Knip from the USA. Hot research areas include intestinal regulation (such as dysbiosis, short chain fatty acids, and probiotics), multisystem ADs (such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease), and immune-related cells (such as T cells, and dendritic cells). Psoriasis, dysbiosis, autoimmune liver disease, and fecal microbiota transplantation may be the future research direction. Our research results can help researchers grasp the current status of ADs and gut microbiota research and find new research directions in the future.

RevDate: 2023-03-01

Guo P, Yang X, Guo X, et al (2023)

Dietary fish oil improves autistic behaviors and gut homeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome.

Brain, behavior, and immunity pii:S0889-1591(23)00050-8 [Epub ahead of print].

Fragile X syndrome (FXS) is the most common inherited intellectual disability, caused by a lack of the fragile X mental retardation protein (FMRP). Individuals with neurodevelopmental disorders frequently experience gastrointestinal problems that are primarily linked to gut microbial dysbiosis, inflammation, and increased intestinal permeability. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are non-pharmacological agents that exert potential therapeutic effects against neurological disorders. However, it is unclear whether omega-3 PUFAs improve autistic behaviors in fragile X syndrome (FXS) by altering the gut microbial composition. Here, we describe gastrointestinal problems in Fmr1 knockout (KO) mice. FMRP deficiency causes intestinal homeostasis dysfunction in mice. Fish oil (FO) as a source of omega-3 PUFAs reduces intestinal inflammation but increases the mRNA and protein levels of TJP3 in the colon of juvenile Fmr1 KO mice. Fecal microbiota transplantation from FO-fed Fmr1 KO mice increased the gut abundance of Akkermansia and Gordonibacter in recipient Fmr1 KO mice and improved gut homeostasis and autistic behaviors. Our findings demonstrate that omega-3 PUFAs improve autistic behaviors and gut homeostasis in FMRP-deficient mice by suppressing gut microbiota dysbiosis, thereby presenting a novel therapeutic approach for juvenile FXS treatment.


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

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )