A single alcohol binge impacts on neutrophil function without changes in gut barrier function and gut microbiome composition in healthy volunteers

The gut is hypothesised to play an important role in the development and progression of sepsis. It is however unknown whether the gut microbiome and the gut barrier function is already altered early in sepsis development and whether it is possible to modulate the microbiome in early sepsis. Therefore, a randomised, double blind, placebo-controlled pilot study to examine the alterations of the microbiome and the gut barrier in early sepsis and the influence of a concomitant probiotic intervention on dysbiosis at this early stage of the disease was conducted. Patients with early sepsis, defined as fulfilling the sepsis definition from the 2012 Surviving Sepsis Campaign guidelines but without signs of organ failure, received multispecies probiotic (Winclove 607 based on Omnibiotic® 10 AAD) for 28 days. Gut microbiome composition, function, gut barrier and bacterial translocation were studied. Patients with early sepsis had a significantly lower structural and functional alpha diversity, clustered differently and showed structural alterations on all taxonomic levels. Gut permeability was unaltered but endotoxin, endotoxin binding proteins and peptidoglycans were elevated in early sepsis patients compared to controls. Probiotic intervention successfully increased probiotic strains in stool and led to an improvement of functional diversity. Microbiome composition and function are altered in early sepsis. Probiotic intervention successfully modulates the microbiome and is therefore a promising tool for early intervention in sepsis.

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Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation

Microorganisms ◽

10.3390/microorganisms7090338 ◽

2019 ◽

Vol 7 (9) ◽

pp. 338 ◽

Cited By ~ 4

Author(s):

Prochazkova ◽

Roubalova ◽

Dvorak ◽

Tlaskalova-Hogenova ◽

Cermakova ◽

...

Keyword(s):

Anorexia Nervosa ◽

Gut Microbiome ◽

Barrier Function ◽

Fecal Microbiota Transplantation ◽

Alpha Diversity ◽

Fecal Microbiota ◽

Correct Selection ◽

Microbial Metabolites ◽

Gut Barrier ◽

Gut Barrier Function

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzz048.fs04-05-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Giorgio Casaburi ◽

Sercan Karav ◽

Steve Frese ◽

Bethany Henrick

Keyword(s):

Gut Microbiome ◽

Barrier Function ◽

Bifidobacterium Longum ◽

Epithelial Barrier ◽

Gut Barrier ◽

Shotgun Metagenomics ◽

Single Strain ◽

Colonic Mucin ◽

Gut Barrier Function ◽

Gut Epithelium

Abstract Objectives The gut epithelium is single-celled barrier that employs many different mechanisms that together provide the first line of defense to physically separate the gut epithelium from our gut microbiome. Notably, the epithelial barrier is protected by a mucin layer providing a physical barrier limiting pathogen access to the epithelial monolayer. We sought to assess how changes in the gut microbiome resulting from colonization by a single strain of Bifidobacterium longum subsp. infantis EVC001 could alter gut barrier function. Methods Fecal samples from this trial were assessed for: (1) endotoxin (lipopolysaccharide) concentration; (2) functional contributions to the gut microbiome by shotgun metagenome sequencing; and (3) fecal glycan profiles by mass spectrometry to assess gut epithelial barrier integrity via breakdown of colonic mucin glycoproteins. Results Colonization with Bifidobacterium, including B. infantis EVC001, showed a significant four-fold reduction in fecal endoxtoxin levels and reductions in fecal inflammatory markers (P < 0.05). Shotgun metagenomics identified LPS-producing Enterobacteriaceae as the most significant contributor of virulence factors in the infant gut metagenome. These bacteria (primarily E. coli and Klebsiella spp.) were also significantly correlated with both mucolytic bacteria (e.g., Bacteroides) and the signatures of mucin breakdown, as assessed by mass spectrometric quantification of colonic mucin-derived glycans. Five different colonic-mucin specific glycans (3_1_1_0, 2_1_2_0, 2_1_1_1, 2_1_1_0, and 1_1_0_1) were significantly associated with microbiome composition (P < 0.05). Overall mucin glycans were inversely correlated with Bifidobacteriaceae abundance (Spearman's rho −0.66, FDR-corrected P value 0.04). Conclusions Complex interactions between the degradation of gut barrier function (e.g., mucin), the production of pro-inflammatory endotoxins, and the risk of infection by these bacteria coming in close contact with the gut epithelium suggest that B. infantis EVC001 can play a role in reducing these combined risks for neonates. Funding Sources This work was funded by Evolve Biosystems, Inc.

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Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Clinical Science ◽

10.1042/cs20180087 ◽

2018 ◽

Vol 132 (6) ◽

pp. 701-718 ◽

Cited By ~ 93

Author(s):

Seungbum Kim ◽

Ruby Goel ◽

Ashok Kumar ◽

Yanfei Qi ◽

Gil Lobaton ◽

...

Keyword(s):

Blood Pressure ◽

High Blood Pressure ◽

Gut Microbiome ◽

Barrier Function ◽

Epithelial Barrier ◽

Barrier Dysfunction ◽

Gut Barrier ◽

Fatty Acid Binding ◽

Gut Barrier Function ◽

Junction Protein

Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut–epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.

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