Role of mucus-bacteria interactions in Enterotoxigenic Escherichia coli (ETEC) H10407 virulence and interplay with human microbiome.

The intestinal mucus layer has a dual role in human health constituting a well-known microbial niche that supports gut microbiota maintenance but also acting as a physical barrier against enteric pathogens. Enterotoxigenic Escherichia coli (ETEC), the major agent responsible for traveler's diarrhea, is able to bind and degrade intestinal mucins, representing an important but understudied virulent trait of the pathogen. Using a set of complementary in vitro approaches simulating the human digestive environment, this study aimed to describe how the mucus microenvironment could shape different aspects of the human ETEC strain H10407 pathophysiology, namely its survival, adhesion, virulence gene expression, interleukin-8 induction and interactions with human fecal microbiota. Using the TNO gastrointestinal model (TIM-1) simulating the physicochemical conditions of the human upper gastrointestinal (GI) tract, we reported that mucus secretion and physical surface sustained ETEC survival, probably by helping it to face GI stresses. When integrating the host part in Caco2/HT29-MTX co-culture model, we demonstrated that mucus secreting-cells favored ETEC adhesion and virulence gene expression, but did not impede ETEC Interleukin-8 (IL-8) induction. Furthermore, we proved that mucosal surface did not favor ETEC colonization in a complex gut microbial background simulated in batch fecal experiments. However, the mucus-specific microbiota was widely modified upon the ETEC challenge suggesting its role in the pathogen infectious cycle. Using multi-targeted in vitro approaches, this study supports the major role played by mucus in ETEC pathophysiology, opening avenues in the design of new treatment strategies.

Lentils and Yeast Fibers: A New Strategy to Mitigate Enterotoxigenic Escherichia coli (ETEC) Strain H10407 Virulence?

Dietary fibers exhibit well-known beneficial effects on human health, but their anti-infectious properties against enteric pathogens have been poorly investigated. Enterotoxigenic Escherichia coli (ETEC) is a major food-borne pathogen that causes acute traveler's diarrhea. Its virulence traits mainly rely on adhesion to an epithelial surface, mucus degradation, and the secretion of two enterotoxins associated with intestinal inflammation. With the increasing burden of antibiotic resistance worldwide, there is an imperious need to develop novel alternative strategies to control ETEC infections. This study aimed to investigate, using complementary in vitro approaches, the inhibitory potential of two dietary-fiber-containing products (a lentil extract and yeast cell walls) against the human ETEC reference strain H10407. We showed that the lentil extract decreased toxin production in a dose-dependent manner, reduced pro-inflammatory interleukin-8 production, and modulated mucus-related gene induction in ETEC-infected mucus-secreting intestinal cells. We also report that the yeast product reduced ETEC adhesion to mucin and Caco-2/HT29-MTX cells. Both fiber-containing products strengthened intestinal barrier function and modulated toxin-related gene expression. In a complex human gut microbial background, both products did not elicit a significant effect on ETEC colonization. These pioneering data demonstrate the promising role of dietary fibers in controlling different stages of the ETEC infection process.

In Vitro Microbial Metabolism of (+)-Catechin Reveals Fast and Slow Converters with Individual-Specific Microbial and Metabolite Markers.

The bioavailability of catechin highly relies on gut microbiota which may determine its metabolic profile, resulting in different health outcomes. Here, we investigated in vitro (+)-catechin metabolism by human microbial communities. There were substantial interindividual differences in the metabolic profiles of (+)-catechin, with 5-(3',4'-dihydroxyphenyl)-γ-valerolactone being the major contributor. Furthermore, the microbial metabolic rate of catechin enabled stratification of 12 participants (fast, medium, and slow converters), despite the interference from the strong intrinsic interindividual variability in fecal microbiota. Correlations were established between this stratified population and microbiota features, such as ecosystem diversity. Additionally, fast converters had significantly higher prevalences of amplicon sequence variants (ASVs) with potential capacity of C-ring cleavage (ASV233_Eggerthella and ASV402_Eubacterium), B-ring dihydroxylation (ASV402_Eubacterium), and short-chain fatty acid (SCFA)-producing ASVs. In conclusion, metabolic-capability-based stratification allows us to uncover differences in microbial composition between fast and slow converters, which could help to elucidate interindividual variabilities in the health benefits of catechins.

Mucin as a Functional Niche is a More Important Driver of in Vitro Gut Microbiota Composition and Functionality than Supplementation of Akkermansia m uciniphila.

IMPORTANCE SECTION Research into identification of biomarkers for gut health and ways to modulate the microbiota composition and activity to improve health, has put Akkermansia muciniphila in the spotlight. As a mucin degrader, A. muciniphila colonizes the interesting but not-fully described host-glycan degradation niche., . Plenty of research concerning A. muciniphila has been done, but little is known about its behavior in the complex microbial ecosystem in the colon, about the potential role of mucins to influence A. muciniphila behavior and the impact of its probiotic administration on the microbial ecosystem.This study aimed at investigating the impact of A. muciniphila administration on the endogenous community while also taking into account its nutritional specificity. As such, the effect of A.mucinihpila administration was investigated with and without addition of mucin. This allowed us to elucidate the importance of mucin presence to modulate the efficiency of the probiotic supplementation with A. muciniphila Akkermansia muciniphila is an abundantly present commensal mucin degrading gut bacterium (1 - 4%) , widely distributed among healthy individuals. It has been positioned as a health biomarker and is currently explored as a biotherapeutic agent and next generation probiotic. Preliminary and ongoing research is mostly based on in vivo mouse models and human intervention trials. While these allow the assessment of physiologically relevant endpoints, the analysis of fecal samples presents limitations with respect to the in-depth mechanistic characterization of Akkermansia effects at the level of the microbiome. We aimed to evaluate the effect of A. muciniphila treatment on the endogenous community from four different donors in a validated, controlled in vitro model of the gut microbial ecosystem (SHIME). Taking into account the nutritional specificity of A. muciniphila, and the prebiotic-like action of mucins in the colon environment, the interplay between mucin, A. muciniphila and the endogenous community was investigated. The effects on the microbial community composition and functionality of A. muciniphila supplementation without mucin were limited, whereas mucin addition successfully induced compositional and metabolic changes in the gut microbiota. Indeed, mucin addition resulted in significantly higher acetate, propionate and butyrate production for all four donors, and the increase of several species, including A. muciniphila, Ruminococcus, Clostridium cluster XIVa, and Lachnospiraceae This study revealed that the supplementation of A. muciniphila together with mucin limited the observed prebiotic-like effect of mucin in inducing compositional changes.

The Donor-Dependent and Colon-Region-Dependent Metabolism of (+)-Catechin by Colonic Microbiota in the Simulator of the Human Intestinal Microbial Ecosystem.

The intestinal absorption of dietary catechins is quite low, resulting in most of them being metabolized by gut microbiota in the colon. It has been hypothesized that microbiota-derived metabolites may be partly responsible for the association between catechin consumption and beneficial cardiometabolic effects. Given the profound differences in gut microbiota composition and microbial load between individuals and across different colon regions, this study examined how microbial (+)-catechin metabolite profiles differ between colon regions and individuals. Batch exploration of the interindividual variability in (+)-catechin microbial metabolism resulted in a stratification based on metabolic efficiency: from the 12 tested donor microbiota, we identified a fast- and a slow-converting microbiota that was subsequently inoculated to SHIME, a dynamic model of the human gut. Monitoring of microbial (+)-catechin metabolites from proximal and distal colon compartments with UHPLC-MS and UPLC-IMS-Q-TOF-MS revealed profound donor-dependent and colon-region-dependent metabolite profiles with 5-(3',4'-dihydroxyphenyl)-γ-valerolactone being the largest contributor to differences between the fast- and slow-converting microbiota and the distal colon being a more important region for (+)-catechin metabolism than the proximal colon. Our findings may contribute to further understanding the role of the gut microbiota as a determinant of interindividual variation in pharmacokinetics upon (+)-catechin ingestion.

Biological and Chemical Processes that Lead to Textile Malodour Development.

The development of malodour on clothing is a well-known problem with social, economic and ecological consequences. Many people still think malodour is the result of a lack of hygiene, which causes social stigma and embarrassment. Clothing is washed more frequently due to odour formation or even discarded when permastink develops. The malodour formation process is impacted by many variables and processes throughout the textile lifecycle. The contact with the skin with consequent transfer of microorganisms, volatiles and odour precursors leads to the formation of a distinctive textile microbiome and volatilome. The washing and drying processes further shape the textile microbiome and impact malodour formation. These processes are impacted by interindividual differences and fabric type as well. This review describes the current knowledge on the volatilome and microbiome of the skin, textile and washing machine, the multiple factors that determine malodour formation on textiles and points out what information is still missing.

Mucin degradation niche as a driver of microbiome composition and Akkermansia muciniphila abundance in a dynamic gut model is donor independent.

Akkermansia muciniphila, an abundant mucin degrading intestinal bacterium, has been correlated with human health in various studies. The in vitro SHIME model was used to reach a mechanistic understanding of A. muciniphila's colonization preferences and its response to environmental parameters such as colon pH and mucins. These insight can help to identify the optimal conditions for successful in vivo application. After a period of mucin deprivation, we found that mucin supplementation resulted in significantly different microbial communities, with more Akkermansia, Bacteroides and Ruminococcus. Mucin treatment accounted for 26% of the observed variation in the microbial community at OTU level (P = 0.001), whereas the donor effect was limited (8%) (P = 0.035), indicating mucins to constitute an important ecological niche shaping the microbiota composition. The effect of colonic pH had a less profound impact on the microbiome with both pH and donor origin explaining around 10% of the variability in the dataset. Yet, higher simulated colonic pH had a positive impact on Akkermansia abundance while short chain fatty acid analysis displayed a preference for propionate production with higher colonic pH. Our results show that mucins as nutritional resource are a more important modulator of the gut microbiome than colon pH as environmental factor.

Mucosa-associated biohydrogenating microbes protect the simulated colon microbiome from stress associated with high concentrations of poly-unsaturated fat.

Polyunsaturated fatty acids (PUFAs) may affect colon microbiome homeostasis by exerting (specific) antimicrobial effects and/or interfering with mucosal biofilm formation at the gut mucosal interface. We used standardized batch incubations and the Mucosal-Simulator of the Human Microbial Intestinal Ecosystem (M-SHIME) to show the in vitro luminal and mucosal effects of the main PUFA in the Western diet, linoleic acid (LA). High concentrations of LA were found to decrease butyrate production and Faecalibacterium prausnitzii numbers dependent on LA biohydrogenation to vaccenic acid (VA) and stearic acid (SA). In faecal batch incubations, LA biohydrogenation and butyrate production were positively correlated and SA did not inhibit butyrate production. In the M-SHIME, addition of a mucosal environment stimulated biohydrogenation to SA and protected F. prausnitzii from inhibition by LA. This was probably due to the preference of two biohydrogenating genera Roseburia and Pseudobutyrivibrio for the mucosal niche. Co-culture batch incubations using Roseburia hominis and F. prausnitzii validated these observations. Correlations networks further uncovered the central role of Roseburia and Pseudobutyrivibrio in protecting luminal and mucosal SHIME microbiota from LA-induced stress. Our results confirm how cross-shielding interactions provide resilience to the microbiome and demonstrate the importance of biohydrogenating, mucosal bacteria for recovery from LA stress.