Interplay between microbial-derived GABA and host GABA receptor signaling collectively influence the tumorigenic function of GABA in colon cancer.

Although classically recognized as a neurotransmitter, gamma aminobutyric acid (GABA) has also been identified in colonic tumors. Moreover, the gut microbiome represents another potential source of GABA. Both GABAA and GABAB receptors have been implicated in contributing to the effects of GABA in colorectal cancer, with both pro- and anti-tumorigenic functions identified. However, their subunit composition is often overlooked. Studies to date have not addressed whether the GABA-producing potential of the microbiome changes over the course of colon tumor development or whether receptor subunit expression patterns are altered in colon cancer. Therefore, we investigated the clusters of orthologous group frequencies of glutamate decarboxylase (GAD) in feces from two murine models of colon cancer and found that the frequency of microbial GAD was significantly decreased early in the tumorigenic process. We also determined that microbial-derived GABA inhibited proliferation of colon cancer cells in vitro and that this effect of GABA on SW480 cells involved both GABAA and GABAB receptors. GABA also inhibited prostaglandin E2 (PGE2)-induced proliferation and interleukin-6 (IL-6) expression in these cells. Gene expression correlations were assessed using the "Cancer Exploration" suite of the TIMER2.0 web tool and identified that GABA receptor subunits were differentially expressed in human colon cancer. Moreover, GABAA receptor subunits were predominantly positively associated with PGE2 synthase, cyclooxygenase-2 and IL-6. Collectively, these data demonstrate decreased potential of the microbiome to produce GABA during tumorigenesis, a novel anti-tumorigenic pathway for GABA, and that GABA receptor subunit expression adds a further layer of complexity to GABAergic signaling in colon cancer.

Akkermansia muciniphila in infectious disease: A new target for this next-generation probiotic?

The common gastrointestinal commensal Akkermansia muciniphila is a mucin-degrading bacterium that is greatly reduced in individuals consuming a high-fat diet. Increasing evidence from a variety of clinical and pre-clinical studies suggests that oral supplementation with Akkermansia can improve metabolic health and moderate systemic inflammation. We and others have demonstrated a role for Akkermansia administration in protection against infectious disease and the outcome from sepsis. Very recent studies have indicated the molecular mechanisms by which A. muciniphila may interact with the host to influence systemic immune-regulation and control of microbial pathogenesis. Here we consider recent studies which demonstrate the efficacy of this potential next-generation probiotic in animal models of Salmonella Typhimurium, Listeria monocytogenes and Clostridioides difficile as well as influenza virus and phlebovirus. The potential mechanisms by which A. muciniphila may influence local and systemic immune responses are discussed.

Akkermansia muciniphila reduces susceptibility to Listeria monocytogenes infection in mice fed a high-fat diet.

A high-fat (HF) diet reduces resistance to the foodborne pathogen Listeria monocytogenes. We demonstrate that short-term gavage with A. muciniphila increases resistance to oral and systemic L. monocytogenes infection in mice fed a HF diet. A. muciniphila reduced inflammation in the gut and liver of mice fed a high-fat diet prior to infection and reduced inflammatory cell infiltration in the ileum to levels similar to mice fed a low-fat (LF) diet. Akkermansia administration had minimal impacts upon the microbiota and microbial metabolites and did not affect individual taxa or impact the Bacteroidetes to Firmicutes ratio. In summary, A. muciniphila increased resistance to L. monocytogenes infection in mice fed a HF diet by moderating immune/physiological effects through specific interaction between A. muciniphila and the host gut.

Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance.

Globally, enteropathogenic bacteria are a major cause of morbidity and mortality.1-3 Campylobacter, Salmonella, Shiga-toxin-producing Escherichia coli, and Listeria are among the top five most commonly reported zoonotic pathogens in the European Union.4 However, not all individuals naturally exposed to enteropathogens go on to develop disease. This protection is attributable to colonization resistance (CR) conferred by the gut microbiota, as well as an array of physical, chemical, and immunological barriers that limit infection. Despite their importance for human health, a detailed understanding of gastrointestinal barriers to infection is lacking, and further research is required to investigate the mechanisms that underpin inter-individual differences in resistance to gastrointestinal infection. Here, we discuss the current mouse models available to study infections by non-typhoidal Salmonella strains, Citrobacter rodentium (as a model for enteropathogenic and enterohemorrhagic E. coli), Listeria monocytogenes, and Campylobacter jejuni. Clostridioides difficile is included as another important cause of enteric disease in which resistance is dependent upon CR. We outline which parameters of human infection are recapitulated in these mouse models, including the impact of CR, disease pathology, disease progression, and mucosal immune response. This will showcase common virulence strategies, highlight mechanistic differences, and help researchers from microbiology, infectiology, microbiome research, and mucosal immunology to select the optimal mouse model.

Quorum sensing in human gut and food microbiomes: Significance and potential for therapeutic targeting.

Human gut and food microbiomes interact during digestion. The outcome of these interactions influences the taxonomical composition and functional capacity of the resident human gut microbiome, with potential consequential impacts on health and disease. Microbe-microbe interactions between the resident and introduced microbiomes, which likely influence host colonisation, are orchestrated by environmental conditions, elements of the food matrix, host-associated factors as well as social cues from other microorganisms. Quorum sensing is one example of a social cue that allows bacterial communities to regulate genetic expression based on their respective population density and has emerged as an attractive target for therapeutic intervention. By interfering with bacterial quorum sensing, for instance, enzymatic degradation of signalling molecules (quorum quenching) or the application of quorum sensing inhibitory compounds, it may be possible to modulate the microbial composition of communities of interest without incurring negative effects associated with traditional antimicrobial approaches. In this review, we summarise and critically discuss the literature relating to quorum sensing from the perspective of the interactions between the food and human gut microbiome, providing a general overview of the current understanding of the prevalence and influence of quorum sensing in this context, and assessing the potential for therapeutic targeting of quorum sensing mechanisms.

Microbial bile salt hydrolase activity influences gene expression profiles and gastrointestinal maturation in infant mice.

The mechanisms by which early microbial colonizers of the neonate influence gut development are poorly understood. Bacterial bile salt hydrolase (BSH) acts as a putative colonization factor that influences bile acid signatures and microbe-host signaling pathways and we considered whether this activity can influence infant gut development. In silico analysis of the human neonatal gut metagenome confirmed that BSH enzyme sequences are present as early as one day postpartum. Gastrointestinal delivery of cloned BSH to immature gnotobiotic mice accelerated shortening of the colon and regularized gene expression profiles, with monocolonised mice more closely resembling conventionally raised animals. In situ expression of BSH decreased markers of cell proliferation (Ki67, Hes2 and Ascl2) and strongly increased expression of ALPI, a marker of cell differentiation and barrier function. These data suggest an evolutionary paradigm whereby microbial BSH activity potentially influences bacterial colonization and in-turn benefits host gastrointestinal maturation.

Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens.

Diseases caused by biofilm-forming pathogens are becoming increasingly prevalent and represent a major threat to human health. This trend has prompted a search for novel inhibitors of microbial biofilms which could, for example, be used to potentiate existing antibiotics. Naturally-occurring, halogenated furanones isolated from marine algae have proven to be effective biofilm inhibitors in several bacterial species. In this work, we report the synthesis of a library of novel furanones and their subsequent evaluation as biofilm inhibitors in several opportunistic human pathogens including S. enterica, S. aureus, E. coli, S. maltophilia, P. aeruginosa and C. albicans. A number of the most potent compounds were subjected to further analysis by confocal laser-scanning microscopy for their effects on P. aeruginosa and C. albicans biofilms individually, in addition to mixed polymicrobial biofilms. Lastly, we investigated the impact of a promising candidate on survival rates in vivo using a Galleria mellonella model.

Comparative Genomics of Lactiplantibacillus plantarum: Insights Into Probiotic Markers in Strains Isolated From the Human Gastrointestinal Tract and Fermented Foods.

Lactiplantibacillus (Lpb.) plantarum is a versatile species commonly found in a wide variety of ecological niches including dairy products and vegetables, while it may also occur as a natural inhabitant of the human gastrointestinal tract. Although Lpb. plantarum strains have been suggested to exert beneficial properties on their host, the precise mechanisms underlying these microbe-host interactions are still obscure. In this context, the genome-scale in silico analysis of putative probiotic bacteria represents a bottom-up approach to identify probiotic biomarkers, predict desirable functional properties, and identify potentially detrimental antibiotic resistance genes. In this study, we characterized the bacterial genomes of three Lpb. plantarum strains isolated from three distinct environments [strain IMC513 (from the human GIT), C904 (from table olives), and LT52 (from raw-milk cheese)]. A whole-genome sequencing was performed combining Illumina short reads with Oxford Nanopore long reads. The phylogenomic analyses suggested the highest relatedness between IMC513 and C904 strains which were both clade 4 strains, with LT52 positioned within clade 5 within the Lpb. plantarum species. The comparative genome analysis performed across several Lpb. plantarum representatives highlighted the genes involved in the key metabolic pathways as well as those encoding potential probiotic features in these new isolates. In particular, our strains varied significantly in genes encoding exopolysaccharide biosynthesis and in contrast to strains IMC513 and C904, the LT52 strain does not encode a Mannose-binding adhesion protein. The LT52 strain is also deficient in genes encoding complete pentose phosphate and the Embden-Meyerhof pathways. Finally, analyses using the CARD and ResFinder databases revealed that none of the strains encode known antibiotic resistance loci. Ultimately, the results provide better insights into the probiotic potential and safety of these three strains and indicate avenues for further mechanistic studies using these isolates.

Impact of Food Origin Lactiplantibacillus plantarum Strains on the Human Intestinal Microbiota in an in vitro System.

We have previously isolated and characterized food-dwelling strains of Lactiplantibacillus (Lpb.) plantarum that are consumed naturally as part of the microbiota of table olives and raw milk cheeses. Despite being consumed at relatively high levels, the impact of such strains on the human gut microbiota is currently unclear. In the current study we evaluated the potential impact of food-dominant Lpb. plantarum strains on the human gut microbiota using a continuous fecal fermentation system. Daily inoculation of Lpb. plantarum strains led to significant, detectable levels in the fecal fermentation system. We examined the impact of the presence of Lpb. plantarum on the microbiota derived from two separate donors. For one donor, Lpb. plantarum increased alpha diversity and beta diversity. This was reflected in significant alterations in abundance of the unclassified genera, dominated by Enterobacteriaceae_unclass and Ruminococcaceae_unclass. The microbiota of the other donor was relatively unaffected following introduction of the Lpb. plantarum strains. Overall, the work describes the response of the human microbiota to the introduction of high levels of food-dominant Lpb. plantarum strains and indicates that the response may reflect interindividual differences between donor samples.

The Influence of the Western Diet on Microbiota and Gastrointestinal Immunity.

Diet exerts a major influence upon host immune function and the gastrointestinal microbiota. Although components of the human diet (including carbohydrates, fats, and proteins) are essential sources of nutrition for the host, they also influence immune function directly through interaction with innate and cell-mediated immune regulatory mechanisms. Regulation of the microbiota community structure also provides a mechanism by which food components influence host immune regulatory processes. Here, we consider the complex interplay between components of the modern (Western) diet, the microbiota, and host immunity in the context of obesity and metabolic disease, inflammatory bowel disease, and infection.

Functional and Phylogenetic Diversity of BSH and PVA Enzymes.

Bile salt hydrolase (BSH) and penicillin V acylase (PVA) are related enzymes that are classified as choloylglycine hydrolases (CGH). BSH enzymes have attracted significant interest for their ability to modulate the composition of the bile acid pool, alter bile acid signaling events mediated by the host bile acid receptors FXR and TGR5 and influence cholesterol homeostasis in the host, while PVA enzymes have been widely utilised in an industrial capacity in the production of semi-synthetic antibiotics. The similarities between BSH and PVA enzymes suggest common evolution of these enzymes and shared mechanisms for substrate binding and catalysis. Here, we compare BSH and PVA through analysis of the distribution, phylogeny and biochemistry of these microbial enzymes. The development of new annotation approaches based upon functional enzyme analyses and the potential implications of BSH enzymes for host health are discussed.

Chitin Attenuates Expression of Listeria monocytogenes Virulence Genes in vitro.

External signals are crucial for bacteria to sense their immediate environment and fine-tune gene expression accordingly. The foodborne pathogen Listeria monocytogenes senses a range of environmental cues in order to activate or deactivate the virulence-inducing transcriptional factor PrfA during transition between infectious and saprophytic lifecycles. Chitin is an abundant biopolymer formed from linked ß-(1-4)-N-acetyl-D-glucosamine residues associated with fungi, the exoskeleton of insects and often incorporated into foods as a thickener or stabilizer. L. monocytogenes evolved to hydrolyse chitin, presumably, to facilitate nutrient acquisition from competitive environments such as soil where the polymer is abundant. Since mammals do not produce chitin, we reasoned that the polymer could serve as an environmental signal contributing to repression of L. monocytogenes PrfA-dependent expression. This study shows a significant downregulation of the core PrfA-regulon during virulence-inducing conditions in vitro in the presence of chitin. Our data suggest this phenomenon occurs through a mechanism that differs from PTS-transport of oligosaccharides generated from either degradation or chitinase-mediated hydrolysis of the polymer. Importantly, an indication that chitin can repress virulence expression of a constitutively active PrfA∗ mutant is shown, possibly mediated via a post-translational modification inhibiting PrfA∗ activity. To our knowledge, this is the first time that chitin is reported as a molecule with anti-virulence properties against a pathogenic bacterium. Thus, our findings identify chitin as a signal which may downregulate the virulence potential of the pathogen and may provide an alternative approach toward reducing disease risk.

Characterizing Phage-Host Interactions in a Simplified Human Intestinal Barrier Model.

An intestinal epithelium model able to produce mucus was developed to provide an environment suitable for testing the therapeutic activity of gut bacteriophages. We show that Enterococcus faecalis adheres more effectively in the presence of mucus, can invade the intestinal epithelia and is able to translocate after damaging tight junctions. Furthermore, Enterococcus phage vB_EfaM_A2 (a member of Herelleviridae that possesses virion associated immunoglobin domains) was found to translocate through the epithelium in the presence and absence of its host bacteria. Phage A2 protected eukaryotic cells by reducing mortality and maintaining the structure of the cell layer structure. We suggest the mammalian cell model utilized within this study as an adaptable in vitro model that can be employed to enable a better understanding of phage-bacteria interactions and the protective impact of phage therapy relating to the intestinal epithelium.

Effectiveness of current hygiene practices on minimization of Listeria monocytogenes in different mushroom production-related environments.

BACKGROUND: The commercial production of Agaricus bisporus is a three stage process: 1) production of compost, also called "substrate"; 2) production of casing soil; and 3) production of the mushrooms. Hygiene practices are undertaken at each stage: pasteurization of the substrate, hygiene practices applied during the production of casing soil, postharvest steam cookout, and disinfection at the mushroom production facilities. However, despite these measures, foodborne pathogens, including Listeria monocytogenes, are reported in the mushroom production environment. In this work, the presence of L. monocytogenes was evaluated before and after the application of hygiene practices at each stage of mushroom production with swabs, samples of substrate, casing, and spent mushroom growing substrates. RESULTS: L. monocytogenes was not detected in any casing or substrate sample by enumeration according to BS EN ISO 11290-2:1998. Analysis of the substrate showed that L. monocytogenes was absent in 10 Phase II samples following pasteurization, but was then present in 40% of 10 Phase III samples. At the casing production facility, 31% of 59 samples were positive. Hygiene improvements were applied, and after four sampling occasions, 22% of 37 samples were positive, but no statistically significant difference was observed (p > .05). At mushroom production facilities, the steam cookout process inactivated L. monocytogenes in the spent growth substrate, but 13% of 15 floor swabs at Company 1 and 19% of 16 floor swabs at Company 2, taken after disinfection, were positive. CONCLUSION: These results showed the possibility of L. monocytogenes recontamination of Phase III substrate, cross-contamination at the casing production stage and possible survival after postharvest hygiene practices at the mushroom growing facilities. This information will support the development of targeted measures to minimize L. monocytogenes in the mushroom industry.

Impact of phospholipid digests and bile acid pool variations on the crystallization of atazanavir from supersaturated solutions.

Oral delivery of poorly water-soluble drugs (PWSDs), which predominate the development pipeline, poses significant challenges. Weakly basic compounds, such as atazanavir, represent a critical class of PWSDs as even the administration of the crystalline solid may invoke supersaturation during gastric-intestinal transfer. The absorption advantage afforded by this supersaturated state can be offset by inherent metastability and a tendency to revert to the lower energy crystalline state. Therefore, it is important to understand the physiological factors that can affect crystallization to improve in vitro-in vivo predictiveness and to regulate inter-individual responses. The first aim of this study was to elucidate the influence of lyso-phosphatidylcholine (lyso-PC) and sodium oleate on crystallization, as the products of phosphatidylcholine (PC) hydrolysis and the major lipid components of human intestinal fluid (HIF) and updated fasted state simulated intestinal fluid version 3 (FaSSIF-V3). Secondly, as an individual's bile acid pool is unique, dynamic and related to gut microbiome community structure, it was of interest to investigate the impact of bile acid pool variations on crystallization from supersaturated solutions. To study the effect of PC hydrolysis, media with 2.8 mM sodium glycocholate (GCA) and sodium taurocholate (TCA) (1:1) but varying concentrations of PC, lyso-PC or sodium oleate were prepared. To investigate the influence of inter-individual variations in intestinal bile acid pool size and composition, media simulating the profiles of six healthy Western volunteers were prepared based on previously published data. The crystalline and amorphous solubility of atazanavir, a weakly basic antiretroviral drug, was firstly determined in these media. Nucleation-induction time experiments were then performed at an equivalent extent of supersaturation in each medium (corresponding to the amorphous solubility). At a constant level of GCA/TCA, increasing concentrations of both PC and lyso-PC accelerated crystallization onset; however, this was at least 2-fold more pronounced with lyso-PC at a given molar concentration. The addition of sodium oleate was also observed to induce crystallization. Interestingly, substituting GCA/TCA with the bile salt fraction of other biorelevant media partially circumvented the crystallization-inducing effect of phospholipids and their digests. The presence of dihydroxy bile salts was found to be particularly significant in decelerating the crystallization process. Nucleation-induction times in simulated volunteer pools were found to be dependent upon bile salt concentration, with higher bile salt levels generally prolonging supersaturation. Differences of up to 6-fold were observed. This study demonstrates that the choice of biorelevant medium used to evaluate supersaturating formulations can influence the observed crystallization kinetics. While the presence of lyso-PC and sodium oleate in FaSSIF-V3 medium is more physiologically relevant, further attention should be paid to the bile salt fraction when designing a biorelevant medium for supersaturating formulations. In vivo, inter-individual differences in the amount and types of bile acids and phospholipids present may influence the behaviour of supersaturating formulations.

When Rhythms Meet the Blues: Circadian Interactions with the Microbiota-Gut-Brain Axis.

The microbiota-gut-brain axis encompasses a bidirectional mode of communication between the microorganisms residing in our gut, and our brain function and behavior. The composition of the gut microbiota is subject to diurnal variation and is entrained by host circadian rhythms. In turn, a diverse microbiota is essential for optimal regulation of host circadian pathways. Disruption of the cyclical nature of this microbe-host interaction profoundly influences disease pathology and severity. This review aims to summarize current knowledge on this bidirectional relationship. Indeed, the past few years have revealed promising data regarding the relationship between the microbiota-gut-brain axis and circadian rhythms and how they act in concert to influence disease, but further research needs to be done to examine how they coalesce to modulate severity of, and risk for, certain diseases. Moreover, there is a need for a greater understanding of the molecular mechanisms underlying the close relationship between circadian-microbiome-brain interactions.

Different carbon sources result in differential activation of sigma B and stress resistance in Listeria monocytogenes.

Listeria monocytogenes is an important food-borne pathogen that is ubiquitous in the environment. It is able to utilize a variety of carbon sources, to produce biofilms on food-processing surfaces and to survive food preservation-associated stresses. In this study, we investigated the effect of three common carbon sources, namely glucose, glycerol and lactose, on growth and activation of the general stress response Sigma factor, SigB, and corresponding phenotypes including stress resistance. A fluorescent reporter coupled to the promoter of lmo2230, a highly SigB-dependent gene, was used to determine SigB activation via quantitative fluorescence spectroscopy. This approach, combined with Western blotting and fluorescence microscopy, showed the highest SigB activation in lactose grown cells and lowest in glucose grown cells. In line with this observation, lactose grown cells showed the highest resistance to lethal heat and acid stress, the highest biofilm formation, and had the highest adhesion/invasion capacity in Caco-2-derived C2Bbe1 cell lines. Our data suggest that lactose utilisation triggers a strong SigB dependent stress response and this may have implications for the resistance of L. monocytogenes along the food chain.

Immunomodulation of J774A.1 Murine Macrophages by Lactiplantibacillus plantarum Strains Isolated From the Human Gastrointestinal Tract and Fermented Foods.

Lactobacillus plantarum species (recently re-named Lactiplantibacillus (Lpb.) plantarum subsp. plantarum) can be isolated from both either the mammalian gut or specific fermented foods where they may be present at high concentrations. Whilst Lpb. plantarum strains have been proposed as potential probiotic candidates, the ability of resident strains consumed in fermented foods to interact with the host is unclear. The main objective of this study was to investigate the cellular location and ability of three different food-borne Lpb. plantarum strains isolated from different sources (table olives and cheese) to modulate the immune response of a murine macrophage-like cell line (J774A.1). For that purpose, macrophages were exposed to the three different Lpb. plantarum strains for 24 h and the expression of a panel of genes involved in the immune response, including genes encoding pattern-recognition receptors (TLRs and NLRs) and cytokines was evaluated by qRT-PCR. We also utilized chemical inhibitors of intracellular pathways to gain some insight into potential signaling mechanisms. Results showed that the native food strains of Lpb. plantarum were able to modulate the response of J774A.1 murine macrophages through a predominately NOD signaling pathway that reflects the transient intracellular location of these strains within the macrophage. The data indicate the capacity of food-dwelling Lpb. plantarum strains to influence macrophage-mediated host responses if consumed in sufficient quantities.

The ability of Listeria monocytogenes to form biofilm on surfaces relevant to the mushroom production environment.

Due to its ubiquitous nature, Listeria monocytogenes is a threat to all fresh fruits and vegetables, including mushrooms, which are Ireland's largest horticultural crop. Although fresh cultivated mushrooms (Agaricus bisporus) have not been previously linked with listeriosis outbreaks, the pathogen still poses a threat to the industry, particularly due to its ability to form biofilms. This threat is highlighted by the multiple recalls of mushroom products caused by L. monocytogenes contamination and by previous studies demonstrating that L. monocytogenes is present in the mushroom production environment. In this study, the biofilm formation potential of L. monocytogenes strains isolated from the mushroom production environment was investigated on materials and at temperatures relevant to mushroom production. A preliminary assessment of biofilm formation of 73 mushroom industry isolates was undertaken using a crystal violet assay on polystyrene microtitre plates. The biofilm formation of a subset (n = 7) of these strains was then assessed on twelve different materials, including materials that are representative of the materials commonly found in the mushroom production environments, using the CDC biofilm reactor. Vertical scanning interferometry was used to determine the surface roughness of the chosen materials. All the strains tested using the CDC biofilm reactor were able to form biofilms on the different surfaces tested but material type was found to be a key determining factor on the levels of biofilm formed. Stainless steel, aluminium, rubber, polypropylene and polycarbonate were all able to support biofilm levels in the range of 4-4.9 log10 CFU/cm2, for seven different L. monocytogenes strains. Mushroom industry-specific materials, including growing nets and tarpaulins, were found to support biofilms levels between 4.7 and 6.7 log10 CFU/cm2. Concrete was found to be of concern as it supported 7.7 log10 CFU/cm2 of biofilm for the same strains; however, sealing the concrete resulted in an approximately 2-log reduction in biofilm levels. The surface roughness of the materials varied greatly between the materials (0.7-3.5 log10 Ra) and was found to have a positive correlation with biofilm formation (rs = 0.573) although marginally significant (P = 0.051). The results of this study indicate that L. monocytogenes can readily form biofilms on mushroom industry relevant surfaces, and additionally identifies surfaces of specific concern, where rigorous cleaning and disinfection is required.

The Cholesterol-Lowering Effect of Oats and Oat Beta Glucan: Modes of Action and Potential Role of Bile Acids and the Microbiome.

Consumption of sufficient quantities of oat products has been shown to reduce host cholesterol and thereby modulate cardiovascular disease risk. The effects are proposed to be mediated by the gel-forming properties of oat ß-glucan which modulates host bile acid and cholesterol metabolism and potentially removes intestinal cholesterol for excretion. However, the gut microbiota has emerged as a major factor regulating cholesterol metabolism in the host. Oat ß-glucan has been shown to modulate the gut microbiota, particularly those bacterial species that influence host bile acid metabolism and production of short chain fatty acids, factors which are regulators of host cholesterol homeostasis. Given a significant role for the gut microbiota in cholesterol metabolism it is likely that the effects of oat ß-glucan on the host are multifaceted and involve regulation of microbe-host interactions at the gut interface. Here we consider the potential for oat ß-glucan to influence microbial populations in the gut with potential consequences for bile acid metabolism, reverse cholesterol transport (RCT), short-chain fatty acid (SCFA) production, bacterial metabolism of cholesterol and microbe-host signaling.