ASSESSMENT OF COLON MICROBIOCENOSIS DISORDERS IN PATIENTS WITH CHRONIC HEPATITIS C.

OBJECTIVE: The aim: To investigate the peculiarities of colon microbiocenosis disorders in patients with chronic hepatitis C. PATIENTS AND METHODS: Materials and methods: 142 patients with CHC were under observation, determination of the degree of liver fibrosis (FibroMax), bacteriological examination of stools and pancreatic elastase was performed. RESULTS: Results: It was found that 59.2% of patients with CHC had gut dysbiosis (DB), of which 61.9% had increased body weight. Intestinal microbiocenosis disorders were manifested by constipation in 57.1% of patients, diarrhea in 31% of patients, and alternating constipation and diarrhea in 11.9% of patients. Bacteriologically, gut dysbiosis was character¬ized by suppression of the growth of normal microflora: Escherichia coli in 47.6%, bifidobacteria in 61.9%, lactobacilli in 53.6%, complete absence of bifidobacteria in 20.2% of cases. In patients with CHC combined with DB deep stages of liver fibrosis (F2-3 and F3-4) are registered 3.6 times more often compared to patients without intestinal dysbiosis (53.6% versus 24.1% and 11.9% versus 3.4%). The degree of gut DB increased in proportion to the stage of liver fibrosis (p<0.05). 32.1% of patients with CHC with dysbiosis were diagnosed with exocrine insufficiency of the pancreas. CONCLUSION: Conclusions: Gut dysbiosis occurs more often in CHC patients with increased body weight and is characterized by constipation in 59.2% of patients. Intestinal microbiocenosis is characterized by suppression of the growth of normal microflora. In 32.1% of CHC patients with intestinal dysbiosis, according to the results of the pancreatic elastase-1 test, pancreatic exocrine insufficiency of various degrees was found.

Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier.

With the rapid development and high therapeutic efficiency and biosafety of gas-involving theranostics, hydrogen medicine has been particularly outstanding because hydrogen gas (H2), a microbial-derived gas, has potent anti-oxidative, anti-apoptotic, and anti-inflammatory activities in many disease models. Studies have suggested that H2-enriched saline/water alleviates colitis in murine models; however, the underlying mechanism remains poorly understood. Despite evidence demonstrating the importance of the microbial hydrogen economy, which reflects the balance between H2-producing (hydrogenogenic) and H2-utilizing (hydrogenotrophic) microbes in maintaining colonic mucosal ecosystems, minimal efforts have been exerted to manipulate relevant H2-microbe interactions for colonic health. Consistent with previous studies, we found that administration of hydrogen-rich saline (HS) ameliorated dextran sulfate sodium-induced acute colitis in a mouse model. Furthermore, we demonstrated that HS administration can increase the abundance of intestinal-specific short-chain fatty acid (SCFA)-producing bacteria and SCFA production, thereby activating the intracellular butyrate sensor peroxisome proliferator-activated receptor γ signaling and decreasing the epithelial expression of Nos2, consequently promoting the recovery of the colonic anaerobic environment. Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in mice with colitis. Exogenous H2 reprograms colonocyte metabolism by regulating the H2-gut microbiota-SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.

Gastrointestinal Digestion Model Assessment of Peptide Diversity and Microbial Fermentation Products of Collagen Hydrolysates.

Osteoarthritis (OA), the most common form of arthritis, is associated with metabolic diseases and gut microbiome dysbiosis. OA patients often take supplements of collagen hydrolysates (CHs) with a high peptide content. Following digestion, some peptides escape absorption to induce prebiotic effects via their colonic fermentation to generate short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs) and colonic gases (NH4 and H2S). The capacity of CHs to generate microbial metabolites is unknown. Proteomic analysis of two CHs (CH-GL and CH-OPT) demonstrated different native peptide profiles with increased peptide diversity after in vitro gastric and small intestinal digestion. Subsequent 24 h fermentation of the CH digests in a dynamic gastrointestinal (GI) digestion model containing human fecal matter showed that CH-OPT increased (p < 0.05) H2S, SCFAs (propionic, butyric and valeric acids), BCFAs, and decreased NH4 in the ascending colon reactor with no major changes seen with CH-GL. No major effects were observed in the transverse and descending vessels for either CH. These findings signify that CHs can induce prebiotic effects in the ascending colon that are CH dependent. More studies are needed to determine the physiological significance of CH-derived colonic metabolites, in view of emerging evidence connecting the gut to OA and metabolic diseases.

A novel technique capable of taking 'protected' biopsies for reliable assessment of the distribution of microbiota along the colonic mucosa.

We evaluated a novel 'protected' biopsy method to reliably ascertain the spatial distribution of the mucosa-adherent colonic microbiota. Apart from minor differences at genus level, overall similarities along the colon were high between the various areas, irrespective of protected or unprotected sampling.

Circulating Short-Chain Fatty Acids Are Positively Associated with Adiposity Measures in Chinese Adults.

Epidemiological studies suggest a positive association between obesity and fecal short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary carbohydrates, while animal models suggest increased energy harvest through colonic SCFA production in obesity. However, there is a lack of human population-based studies with dietary intake data, plasma SCFAs, gut microbial, and anthropometric data. In 490 Chinese adults aged 30-68 years, we examined the associations between key plasma SCFAs (butyrate/isobutyrate, isovalerate, and valerate measured by non-targeted plasma metabolomics) with body mass index (BMI) using multivariable-adjusted linear regression. We then assessed whether overweight (BMI ≥ 24 kg/m2) modified the association between dietary-precursors of SCFAs (insoluble fiber, total carbohydrates, and high-fiber foods) with plasma SCFAs. In a sub-sample (n = 209) with gut metagenome data, we examined the association between gut microbial SCFA-producers with BMI. We found positive associations between butyrate/isobutyrate and BMI (p-value < 0.05). The associations between insoluble fiber and butyrate/isobutyrate differed by overweight (p-value < 0.10). There was no statistical evidence for an association between microbial SCFA-producers and BMI. In sum, plasma SCFAs were positively associated with BMI and that the colonic fermentation of fiber may differ for adults with versus without overweight.

Inulin as a Delivery Vehicle for Targeting Colon-Specific Cancer.

Natural polysaccharides, as well as biopolymers, are now days widely developed for targeting colon cancer using various drug delivery systems. Currently, healing conformations are being explored that can efficiently play a multipurpose role. Owing to the capability of extravagance colonic diseases with the least adverse effects, biopolymers for site specific colon delivery have developed an increased curiosity over the past decades. Inulin (INU) was explored for its probable application as an entrapment material concerning its degradation by enzymes in the colonic microflora and its drug release behavior in a sustained and controlled manner. INU is a polysaccharide and it consists of 2 to 1 linkage having an extensive array of beneficial uses such as a carrier for delivery of therapeutic agents as an indicative/investigative utensil or as a dietary fiber with added well-being aids. In the main, limited research, as well as information, is available on the delivery of therapeutic agents using inulin specifically for colon cancer because of its capability to subsist in the stomach's acidic medium. This exceptional steadiness and robustness properties are exploited in numerous patterns to target drugs securely for the management of colonic cancer, where they effectively act and kills colonic tumor cells easily. In this review article, recent efforts and inulin-based nano-technological approaches for colon cancer targeting are presented and discussed.

IL-13 mRNA Tissue Content Identifies Two Subsets of Adult Ulcerative Colitis Patients With Different Clinical and Mucosa-Associated Microbiota Profiles.

BACKGROUND AND AIMS: A personalized approach to therapy hold great promise to improve disease outcomes. To this end, the identification of different subsets of patients according to the prevalent pathogenic process might guide the choice of therapeutic strategy. We hypothesize that ulcerative colitis [UC] patients might be stratified according to distinctive cytokine profiles and/or to a specific mucosa-associated microbiota. METHODS: In a cohort of clinically and endoscopic active UC patients and controls, we used quantitative PCR to analyse the mucosal cytokine mRNA content and 16S rRNA gene sequencing to assess the mucosa-associated microbiota composition. RESULTS: We demonstrate, by means of data-driven approach, the existence of a specific UC patient subgroup characterized by elevated IL-13 mRNA tissue content separate from patients with low IL-13 mRNA tissue content. The two subsets differ in clinical-pathological characteristics. High IL-13 mRNA patients are younger at diagnosis and have a higher prevalence of extensive colitis than low IL-13 mRNA patients. They also show more frequent use of steroid/immunosuppressant/anti-tumour necrosis factor α therapy during 1 year of follow-up. The two subgroups show differential enrichment of mucosa-associated microbiota genera with a prevalence of Prevotella in patients with high IL-13 mRNA tissue content and Sutterella and Acidaminococcus in patients with low IL-13 mRNA tissue content. CONCLUSION: Assessment of mucosal IL-13 mRNA might help in the identification of a patient subgroup that might benefit from a therapeutic approach modulating IL-13. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Germplasm evaluation to obtain inulin with high degree of polymerization in Mediterranean environment.

Long-chain length (DP) inulin-type fructans show pronounced beneficial effects to colon microbiota. In the past, cardoon roots for inulin production to fortify spaghetti gave very good results, but their harvest requires high costs. The aim of the work was to evaluate different types of inulin, extracted from cardoon roots and buds, topinambur tubers and chicory roots local populations in order to identify crops more suitable for high DP inulin production in Mediterranean environment. The inulin amount resulted in 115 (chicory), 390 (cardoon) and 550 g kg-1 of d.m. (topinambur). Both in cardoon roots and in topinambur tubers the DP was very high. With the aim to produce a functional food, substituting inulin in staple food tubers of topinambur could be a good alternative to cardoon roots, due to the biological cycle of the plant (annual vs poliennal), the lowest costs of harvest and the good amounts of high DP inulin.

Bioavailability assessment of zinc enriched lactobacillus biomass in a human colon carcinoma cell line (Caco-2).

The present study utilizes lactobacilli strains having the potential to accumulate a significant amount of Zinc (Zn) in their biomass and ability to deliver the same mineral in a highly bioavailable form. A human origin Lactobacillus fermentum SR4 and Lactobacillus rhamnosus GG (LGG) were studied for their ability to accumulate Zn by growing them in the medium containing Zn salt. Further, Zn enriched cell lysates were prepared by Ultrasonication, as an organic Zn source. Various functional groups involved in bacterial Zn binding were identified by FT-IR spectroscopy and elemental Zn in bio-chelated cell lysate complex was confirmed by SEM and Energy Dispersive X-ray Spectrometry (EDX). Experimental data demonstrated a significantly higher (P < 0.05) bioavailability of Zn chelated by SR4 followed by LGG i.e., 57% and 48%, as compared to the commercially available inorganic (ZnSo4) and even organic (Zinc gluconate) forms tested which has 15.6% and 21.7% respectively.

Arsenic in Rice Bran Products: In Vitro Oral Bioaccessibility, Arsenic Transformation by Human Gut Microbiota, and Human Health Risk Assessment.

Despite rice consumption, rice bran as a byproduct of rice milling contains higher arsenic (As). The present study evaluated the metabolic potency of in vitro cultured human colon microbiota toward As from five rice bran products with 0.471-1.491 mg of As/kg. Arsenic bioaccessibility ranged from 52.8 to 78.8% in the gastric phase, and a 1.2-fold increase (66.0-95.8%) was observed upon the small intestinal phase. Subsequently, a significant decline of As bioaccessibility (11.3-63.6%) and a high methylation percentage of 18.5-79.8% were found in the colon phase. The predominant As species in the solid phase was always As(V) (49.6-63.4%), and As-thiolate complexes increased by 10% at the end of colon incubation. Human gut microbiota could induce As bioaccessibility lowering and As transformation in rice bran, which illustrated the importance of food-bound As metabolism in the human body. This will result in a better understanding of health implications associated with As exposures.

Oligosaccharide biotechnology: an approach of prebiotic revolution on the industry.

Oligosaccharides are polymers with two to ten monosaccharide residues which have sweetener functions and sensory characteristics, in addition to exerting physiological effects on human health. The ones called nondigestible exhibit a prebiotic behavior being fermented by colonic microflora or stimulating the growth of beneficial bacteria, playing roles in the immune system, protecting against cancer, and preventing cardiovascular and metabolic issues. The global prebiotics market is expected to grow around 12.7% in the next 8 years, so manufacturers are developing new alternatives to obtain sustainable and efficient processes for application on a large scale. Most studied examples of biotechnological processes involve the development of new strategies for fructooligosaccharide, galactooligosaccharide, xylooligosaccharide, and mannanooligosaccharide synthesis. Among these, the use of whole cells in fermentation, synthesis of microbial enzymes (ß-fructofuranosidases, ß-galactosidases, xylanases, and ß-mannanases), and enzymatic process development (permeabilization, immobilization, gene expression) can be highlighted, especially if the production costs are reduced by the use of agro-industrial residues or by-products such as molasses, milk whey, cotton stalks, corncobs, wheat straw, poplar wood, sugarcane bagasse, and copra meal. This review comprises recent studies to demonstrate the potential for biotechnological production of oligosaccharides, and also aspects that need more investigation for future applications in a large scale.

Race-dependent association of sulfidogenic bacteria with colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) incidence is higher in African Americans (AAs) compared with non-Hispanic whites (NHWs). A diet high in animal protein and fat is an environmental risk factor for CRC development. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC. Hydrogen sulfide, produced by autochthonous sulfidogenic bacteria, triggers proinflammatory pathways and hyperproliferation, and is genotoxic. We hypothesised that sulfidogenic bacterial abundance in colonic mucosa may be an environmental CRC risk factor that distinguishes AA and NHW. DESIGN: Colonic biopsies from uninvolved or healthy mucosa from CRC cases and tumour-free controls were collected prospectively from five medical centres in Chicago for association studies. Sulfidogenic bacterial abundance in uninvolved colonic mucosa of AA and NHW CRC cases was compared with normal mucosa of AA and NHW controls. In addition, 16S rDNA sequencing was performed in AA cases and controls. Correlations were examined among bacterial targets, race, disease status and dietary intake. RESULTS: AAs harboured a greater abundance of sulfidogenic bacteria compared with NHWs regardless of disease status. Bilophila wadsworthia-specific dsrA was more abundant in AA cases than controls. Linear discriminant analysis of 16S rRNA gene sequences revealed five sulfidogenic genera that were more abundant in AA cases. Fat and protein intake and daily servings of meat were significantly higher in AAs compared with NHWs, and multiple dietary components correlated with a higher abundance of sulfidogenic bacteria. CONCLUSIONS: These results implicate sulfidogenic bacteria as a potential environmental risk factor contributing to CRC development in AAs.

Extending colonic mucosal microbiome analysis-assessment of colonic lavage as a proxy for endoscopic colonic biopsies.

BACKGROUND: Sequencing-based analysis has become a well-established approach to deciphering the composition of the gut microbiota. However, due to the complexity of accessing sufficient material from colonoscopic biopsy samples, most studies have focused on faecal microbiota analysis, even though it is recognised that differences exist between the microbial composition of colonic biopsies and faecal samples. We determined the suitability of colonic lavage samples to see if it had comparable microbial diversity composition to colonic biopsies as they are without the limitations associated with sample size. We collected paired colonic biopsies and lavage samples from subjects who were attending for colorectal cancer screening colonoscopy. RESULTS: Next-generation sequencing and qPCR validation were performed with multiple bioinformatics analyses to determine the composition and predict function of the microbiota. Colonic lavage samples contained significantly higher numbers of operational taxonomic units (OTUs) compared to corresponding biopsy samples, however, diversity and evenness between lavage and biopsy samples were similar. The differences seen were driven by the presence of 12 OTUs which were in higher relative abundance in biopsies and were either not present or in low relative abundance in lavage samples, whilst a further 3 OTUs were present in higher amounts in the lavage samples compared to biopsy samples. However, predicted functional community profiling based on 16S ribosomal ribonucleic acid (rRNA) data indicated minimal differences between sample types. CONCLUSIONS: We propose that colonic lavage samples provide a relatively accurate representation of biopsy microbiota composition and should be considered where biopsy size is an issue.

Lower Neighborhood Socioeconomic Status Associated with Reduced Diversity of the Colonic Microbiota in Healthy Adults.

In the United States, there are persistent and widening socioeconomic gaps in morbidity and mortality from chronic diseases. Although most disparities research focuses on person-level socioeconomic-status, mounting evidence suggest that chronic diseases also pattern by the demographic characteristics of neighborhoods. Yet the biological mechanisms underlying these associations are poorly understood. There is increasing recognition that chronic diseases share common pathogenic features, some of which involve alterations in the composition, diversity, and functioning of the gut microbiota. This study examined whether socioeconomic-status was associated with alpha-diversity of the colonic microbiota. Forty-four healthy adults underwent un-prepped sigmoidoscopy, during which mucosal biopsies and fecal samples were collected. Subjects' zip codes were geocoded, and census data was used to form a composite indicator of neighborhood socioeconomic-status, reflecting household income, educational attainment, employment status, and home value. In unadjusted analyses, neighborhood socioeconomic-status explained 12-18 percent of the variability in alpha-diversity of colonic microbiota. The direction of these associations was positive, meaning that as neighborhood socioeconomic-status increased, so did alpha-diversity of both the colonic sigmoid mucosa and fecal microbiota. The strength of these associations persisted when models were expanded to include covariates reflecting potential demographic (age, gender, race/ethnicity) and lifestyle (adiposity, alcohol use, smoking) confounds. In these models neighborhood socioeconomic-status continued to explain 11-22 percent of the variability in diversity indicators. Further analyses suggested these patterns reflected socioeconomic variations in evenness, but not richness, of microbial communities residing in the sigmoid. We also found indications that residence in neighborhoods of higher socioeconomic-status was associated with a greater abundance of Bacteroides and a lower abundance of Prevotella, suggesting that diet potentially underlies differences in microbiota composition. These findings suggest the presence of socioeconomic variations in colonic microbiota diversity. Future research should explore whether these variations contribute to disparities in chronic disease outcomes.

[Assessment of the impact of vitamin and dietary fiber content in the diet on the characteristics of protective colon microbiota populations of rats].

The content of lactobacilli and enterobacteria in the experiment in rats with varying levels of vitamins and dietary fiber was studied. The study was performed on 48 male weanling Wistar rats randomized into 8 groups, with the creation of vitamin deficiency (30 d.) and its further compensation (5 d.). Vitamin content in the semisynthetic diet in rats of the control group N 1 corresponded to 100% of a daily adequate intake. In the similar composition of the diet of the control group N 2 wheat bran was added in amount of 5% of the weight of the diet. In groups N 3­8 rats received a diet with the reduced amount of vitamin mixture by 5 times (20% of the adequate intake) and the total exclusion of tocopherol, thiamine and riboflavin from the mixture. The wheat bran (5% of diet mass) was added to the diets in Groups N 4, 6, 8. At the stage of compensation of deficiency rats were fed with the diets with increased content of vitamin mixture: Group 5­6 to 80% 7­8 to 200% (100 and 220% of the adequate intake, respectively), and the groups N 3­4 continued to receive deficient diet with or without wheat bran until the end of the experiment. After 35 days rats were anesthetized with ether, decapitated, necropsied and the cecum segments were selected for quantitative microbiological analysis of its contents. It has been shown that the addition of wheat bran to vitamin deficient diet lead to the reduction of the manifestation of physical sign of hypovitaminosis. It also eliminated the differences in the integrated index of growth and development of rats in comparison with the group without vitamin deficiency. It was found that the vitamin deficiency in the diet, regardless of the presence or absence of wheat bran, led to a significant reduction of the number of lactobacilli in the intestinal contents, but almost did not affect the number of normal and opportunistic pathogenic enterobacteria. The compensation of deficiency during 5 days lead to the increased number of lactobacilli, but the physiological levels and levels in control animals it reached only in rats received 220% of the vitamins with the addition of wheat bran. In the lactobacilli population in all rats received different doses of vitamins (including reduced to 20%), regardless of the presence of wheat bran, prevailing culturable representatives were 3 kinds of Lactobacillus spp. ­ acidophilus, fermentum, paracasei. These species showed stable presence in the intestine even in conditions of prolonged vitamin deficiency (35 days). L. acidophilus was the dominated lactoflora representative in all rats, its' content was average 91.7% of all culturable lactobacilli. With less constancy and in lower amounts were detected L. plantarum and representatives of coccal flora (Leuconostoc lactis, Lactococcus lactis).

Evaluation of an in vitro faecal degradation method for early assessment of the impact of colonic degradation on colonic absorption in humans.

The objective of this study was to develop and evaluate an in vitro method to investigate bacterial-mediated luminal degradation of drugs in colon in humans. This would be a valuable tool for the assessment of drug candidates during early drug development, especially for compounds intended to be developed as oral extended release formulations. Freshly prepared faecal homogenate from healthy human volunteers (n=3-18), dog (n=6) and rat (colon and caecal content, n=3) was homogenised with 3.8 parts (w/w) physiological saline under anaerobical conditions. Four model compounds (almokalant, budesonide, ximelagatran and metoprolol) were then incubated (n=3-18) separately in the human faecal homogenate for up to 120min at 37°C. In addition, ximelagatran was also incubated in the faecal or colonic content from dog and rat. The mean (±SD) in vitro half-life for almokalant, budesonide and ximelagatran was 39±1, 68±21 and 26±12min, respectively, in the human faecal homogenate. Metoprolol was found to be stable in the in vitro model. The in vitro degradation data was then compared to literature data on fraction absorbed after direct colon administration in humans. The percentage of drug remaining after 60min of in vitro incubation correlated (R(2)=0.90) with the fraction absorbed from colon in humans. The mean in vitro half-life of ximelagatran was similar in human faeces (26±12min) and rat colon content (34±31min), but significantly (p<0.05) longer in rat caecum content (50±11min) and dog faeces (126±17min). The in vitro method is in vivo relevant both qualitatively as all the model drugs that undergoes colonic degradation in vivo was rapidly degraded in the faecal homogenates as well as quantitatively since a correlation was established between percentage degraded in vitro at 60min and fraction absorbed in the colon for the model drugs, which have no other absorption limiting properties. Also, the method is easy to use from a technical point of view, which suggests that the method is suitable for use in early assessment of colonic absorption of extended release formulation candidates. Further improvement of the confidence in the use of the method would either require an extension of the correlation, which most likely will require more human regional absorption studies, or by including colonic degradation rate as an input in a physiological mechanistic absorption model and evaluate if the prediction of the plasma exposure after colonic administration of the present model drugs is improved.

LC-MS/MS method for rapid and concomitant quantification of pro-inflammatory and pro-resolving polyunsaturated fatty acid metabolites.

Lipid autacoids derived from n-3/n-6 polyunsaturated fatty acids (PUFA) are some of the earliest signals triggered by an inflammatory reaction. They are acting also as essential regulators of numerous biological processes in physiological conditions. With regards to their importance, a robust and rapid procedure to quantify a large variety of PUFA metabolites, applicable to diverse biological components needed to be formulated. We have developed a simple methodology using liquid chromatography-tandem mass spectrometry allowing quantification of low-level of PUFA metabolites including bioactive mediators, inactive products and pathway biomarkers. Solid phase extraction was used for samples preparation with an extraction yield of 80% ranging from 65% to 98%. The method was optimized to obtain a rapid (8.5min) and accurate separation of 26 molecules, with a very high sensitivity of detection and analysis (0.6-155pg). When applied to biological samples, the method enabled characterization of eicosanoids and docosanoids production in epithelial cells or foam macrophages stimulated with LPS, in biological fluids and tissues from mouse models of peritonitis or infectious colitis. Our results demonstrate that this new method can be used in cultured cells, in fluids and in colonic tissues to quantify pro-inflammatory and pro-resolving PUFA metabolites mediators.

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model.

The human gut is colonized by a complex microbiota with multiple benefits. Although the surface-attached, mucosal microbiota has a unique composition and potential to influence human health, it remains difficult to study in vivo. Therefore, we performed an in-depth microbial characterization (human intestinal tract chip (HITChip)) of a recently developed dynamic in vitro gut model, which simulates both luminal and mucosal gut microbes (mucosal-simulator of human intestinal microbial ecosystem (M-SHIME)). Inter-individual differences among human subjects were confirmed and microbial patterns unique for each individual were preserved in vitro. Furthermore, in correspondence with in vivo studies, Bacteroidetes and Proteobacteria were enriched in the luminal content while Firmicutes rather colonized the mucin layer, with Clostridium cluster XIVa accounting for almost 60% of the mucin-adhered microbiota. Of the many acetate and/or lactate-converting butyrate producers within this cluster, Roseburia intestinalis and Eubacterium rectale most specifically colonized mucins. These 16S rRNA gene-based results were confirmed at a functional level as butyryl-CoA:acetate-CoA transferase gene sequences belonged to different species in the luminal as opposed to the mucin-adhered microbiota, with Roseburia species governing the mucosal butyrate production. Correspondingly, the simulated mucosal environment induced a shift from acetate towards butyrate. As not only inter-individual differences were preserved but also because compared with conventional models, washout of relevant mucin-adhered microbes was avoided, simulating the mucosal gut microbiota represents a breakthrough in modeling and mechanistically studying the human intestinal microbiome in health and disease. Finally, as mucosal butyrate producers produce butyrate close to the epithelium, they may enhance butyrate bioavailability, which could be useful in treating diseases, such as inflammatory bowel disease.