Humans depend upon our commensal bacteria for nutritive, immune-modulating and metabolic contributions to maintenance of health. However, this commensal community exists in careful balance that, if disrupted, enters dysbiosis; which has been shown to contribute to the etiology of colon, gastric, esophageal, pancreatic, laryngeal, breast and gallbladder carcinomas. This etiology is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis while increasing vulnerability to pathogens. Advances in sequencing technology have increased our ability to catalog microbial species associated with various cancer types across the body. However, defining microbial biomarkers as cancer predictors presents multiple challenges and existing studies identifying cancer-associated bacteria have reported inconsistent outcomes. Combining metabolites and microbiome analyses can help elucidate interactions between gut microbiota, metabolism and the host. Ultimately, understanding how gut dysbiosis impacts host response and inflammation will be critical to creating an accurate picture of the role of the microbiome in cancer.

Scope Heat-stabilized rice bran and cooked navy bean powder contain a variety of phytochemicals that are fermented by colonic microbiota and may influence intestinal health. Dietary interventions with these foods should be explored for modulating colorectal cancer risk. Methods and results A randomized-controlled pilot clinical trial investigated the effects of eating heat-stabilized rice bran (30g/day) or cooked navy bean powder (35g/day) on gut microbiota and metabolites (NCT01929122). Twenty-nine overweight/obese volunteers with a prior history of colorectal cancer consumed a study-provided meal and snack daily for 28 days. Volunteers receiving rice bran or bean powder showed increased gut bacterial diversity and altered gut microbial composition at 28 days compared to baseline. Supplementation with rice bran or bean powder increased total dietary fiber intake similarly, yet only rice bran intake led to a decreased Firmicutes:Bacteroidetes ratio and increased short chain fatty acids (propionate and acetate) in stool after 14 days but not at 28 days. Conclusion These findings support modulation of gut microbiota and fermentation by-products by heat-stabilized rice bran and suggest that foods with similar ability to increase dietary fiber intake may not have equal effects on gut microbiota and microbial metabolism.

Interactions between the microbiota and distal gut are important for the maintenance of a healthy intestinal barrier; dysbiosis of intestinal microbial communities has emerged as a likely contributor to diseases that arise at the level of the mucosa. Intraepithelial lymphocytes (IELs) are positioned within the epithelial barrier, and in the small intestine, function to maintain epithelial homeostasis. We hypothesized that colonic IELs promote epithelial barrier function through the expression of cytokines in response to interactions with commensal bacteria. 16S rRNA profiling revealed that candidate bacteria in the order Bacteroidales are sufficient to promote IEL presence in the colon, which in turn, produce IL-6 in a MyD88-dependent fashion. IEL-derived IL-6 is functionally important in the maintenance of the epithelial barrier as IL-6−/− mice were noted to have increased paracellular permeability, decreased claudin-1 expression, and a thinner mucus-gel layer, all of which were reversed by transfer of IL-6+/+ IELs, leading to protection of mice in response to Citrobacter rodentium infection. Therefore, we conclude that microbiota provide a homeostatic role for epithelial barrier function through regulation of IEL-derived IL-6.

BackgroundPrevious studies have highlighted the antimicrobial activity of caffeine, both individually and in combination with other compounds. A proposed mechanism for caffeine’s antimicrobial effects is inhibition of bacterial DNA repair pathways. The current study examines the influence of sub-lethal caffeine levels on the growth and morphology of SOS response pathway mutants of Escherichia coli.MethodsGrowth inhibition after treatment with caffeine and methyl methane sulfonate (MMS), a mutagenic agent, was determined for E. coli mutants lacking key genes in the SOS response pathway. The persistence of caffeine’s effects was explored by examining growth and morphology of caffeine and MMS-treated bacterial isolates in the absence of selective pressure.ResultsCaffeine significantly reduced growth of E. coli recA- and uvrA-mutants treated with MMS. However, there was no significant difference in growth between umuC-isolates treated with MMS alone and MMS in combination with caffeine after 48 h of incubation. When recA-isolates from each treatment group were grown in untreated medium, bacterial isolates that had been exposed to MMS or MMS with caffeine showed increased growth relative to controls and caffeine-treated isolates. Morphologically, recA-isolates that had been treated with caffeine and both caffeine and MMS together had begun to display filamentous growth.ConclusionsCaffeine treatment further reduced growth of recA- and uvrA-mutants treated with MMS, despite a non-functional SOS response pathway. However, addition of caffeine had very little effect on MMS inhibition of umuC-mutants. Thus, growth inhibition of E. coli with caffeine treatment may be driven by caffeine interaction with UmuC, but also appears to induce damage by additional mechanisms as evidenced by the additive effects of caffeine in recA- and uvrA-mutants.

Interactions between the microbiota and distal gut are important for the maintenance of a healthy immune system. Dysbiosis of colon bacteria has emerged as a likely contributor to diseases that arise at the level of the mucosa. Intraepithelial lymphocytes (IELs) are positioned within the epithelial barrier, and in the small intestine, function to maintain epithelial homeostasis. We hypothesized that IELs of the colon modulate epithelial barrier function through the liberation of cytokines stimulated by interactions with resident bacteria. Our data demonstrate that IL-6 is a major cytokine secreted by colonic IELs in a microbe-dependent fashion. We identify Alistipes species of the phylum Bacteroidetes as candidates to recruit IELs and stimulate their IL-6 secretion. IEL-derived IL-6 is functionally important in the maintenance of the epithelial barrier as IL-6−/− and antibiotic-treated mice were noted to have increased paracellular permeability and closer interaction with luminal bacteria. IL-6 was found to signal in colonic epithelial cells and resulted in increased epithelial barrier integrity and claudin1 expression in model epithelia. Therefore, we conclude that the host microbiota provides a homeostatic role for epithelial barrier function through regulation of IEL derived IL-6.