SUMMARY Dietary soluble fibers are fermented by gut bacteria into short-chain fatty acids (SCFA), which are considered broadly health-promoting. Accordingly, consumption of such fibers ameliorates metabolic syndrome. However, incorporating soluble fiber inulin, but not insoluble fiber, into a compositionally defined diet, induced icteric hepatocellular carcinoma (HCC). Such HCC was microbiota-dependent and observed in multiple strains of dysbiotic mice but not in germ-free nor antibiotics-treated mice. Furthermore, consumption of an inulin-enriched high-fat diet induced both dysbiosis and HCC in wild-type (WT) mice. Inulin-induced HCC progressed via early onset of cholestasis, hepatocyte death, followed by neutrophilic inflammation in liver. Pharmacologic inhibition of fermentation or depletion of fermenting bacteria markedly reduced intestinal SCFA and prevented HCC. Intervening with cholestyramine to prevent reabsorption of bile acids also conferred protection against such HCC. Thus, its benefits notwithstanding, enrichment of foods with fermentable fiber should be approached with great caution as it may increase risk of HCC.

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After a brief history of ergot alkaloids and ergotism, this review focuses on the metabolism and mechanisms of action of the ergot alkaloids. The authors provide models of how these alkaloids afflict grazing livestock under complex animal-plant/endophyte-environmental interactions. Alkaloid chemistry is presented to orient the reader to the structure-function relationships that are known to exist. Where appropriate, the medical literature is used to aid interpretation of livestock research and to provide insight into potential modes of action and alkaloid metabolism where these are not known for livestock. In closing the paper, we discuss management of ergot alkaloid intoxication in livestock and future research needs for this field of study.

ObjectiveDiets rich in fermentable fibres provide an array of health benefits; however, many patients with IBD report poor tolerance to fermentable fibre-rich foods. Intervention studies with dietary fibres in murine models of colonic inflammation have yielded conflicting results on whether fibres ameliorate or exacerbate IBD. Herein, we examined how replacing the insoluble fibre, cellulose, with the fermentable fibres, inulin or pectin, impacted murine colitis resulting from immune dysregulation via inhibition of interleukin (IL)-10 signalling and/or innate immune deficiency (Tlr5KO).DesignMice were fed with diet containing either cellulose, inulin or pectin and subjected to weekly injections of an IL-10 receptor (αIL-10R) neutralising antibody. Colitis development was examined by serological, biochemical, histological and immunological parameters.ResultsInulin potentiated the severity of αIL10R-induced colitis, while pectin ameliorated the disease. Such exacerbation of colitis following inulin feeding was associated with enrichment of butyrate-producing bacteria and elevated levels of caecal butyrate. Blockade of butyrate production by either metronidazole or hops β-acids ameliorated colitis severity in inulin-fed mice, whereas augmenting caecal butyrate via tributyrin increased colitis severity in cellulose containing diet-fed mice. Elevated butyrate levels were associated with increased IL-1β activity, while inhibition of the NOD-like receptor protein 3 by genetic, pharmacologic or dietary means markedly reduced colitis.ConclusionThese results not only support the notion that fermentable fibres have the potential to ameliorate colitis but also caution that, in some contexts, prebiotic fibres can lead to gut dysbiosis and surfeit colonic butyrate that might exacerbate IBD.

Ruminal proteolysis and subsequent amino acid degradation represent considerable economic loss in ruminant production. The hyper ammonia-producing bacteria (HAB) are largely responsible for amino acid deamination in the rumen. HAB can be controlled with ionophores, but they are also susceptible to antimicrobial plant secondary metabolites. Red clover (Trifolium pratense) is rich in soluble phenolics, and it is also more resistant to proteolysis than other legumes. The goal of this study was to identify phenolic compounds from Trifolium pratense cultivar Kenland, and determine if any of the compounds possessed antimicrobial activity against the bovine HAB, Clostridium sticklandii SR. HPLC analysis revealed that clover tissues were rich in the isoflavonoids formononetin and biochanin A, particularly in plants left to wilt for 24 h. Biochanin A inhibited C. sticklandii in bioassays that employed thin-layer chromatography (TLC). Both clover extracts and biochanin A inhibited the growth of C. sticklandii in broth culture, but formononetin had no effect. These results indicate that clover phenolic compounds may have a role in preventing amino acid fermentation.