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Gut Microbiota & Short Chain Fatty Acids

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Gut Microbiota & Short Chain Fatty Acids GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM GUT MICROBIOTA & SHORT CHAIN FATTY ACIDS A selection of content from the Gut Microbiota for Health 2016 March 2017 www.gutmicrobiotaforhealth.com TABLE OF CONTENT EDITORIAL 3 SELECTED CONTENT FROM GUTMICROBIOTAFORHEALTH.COM • Dietary fibre/short-chain fatty acids and vitamin A may protect mice against peanut allergy via gut microbiota 6 • Fitness may predict a diverse gut microbiota in healthy people 8 • An update on the link between short-chain fatty acids, diet, and human health 10 • The role of gut microbiota composition and microbial metabolites in fat partitioning and carbohydrate metabolism in youth 12 • The role of short-chain fatty acids in driving obesity: Should we blame acetate? 14 • Conserving and restoring the human gut microbiome by increasing consumption of dietary fibre 16 • Mice study shows low-fibre diet may decimate gut bacteria diversity over generations 18 GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM 2 EDITORIAL In searching for the molecular SCFAs (in particular, butyrate) mechanisms connecting dietary regulate the AP-1 signaling path- fibre to positive gastrointestinal way (Nepelska et al., 2012). and metabolic effects and lower body weight (Slavin, 2013), Butyrate indeed stands out as an research in the past several important SCFA for regulating decades has centred around a gene expression in the intestine. group of molecules called short- Our group previously found that chain fatty acids (SCFAs), which MUC gene expression and mucin are produced by bacteria when secretion were regulated by they ferment non-digestible carbo- butyrate: its effects on different hydrates. As a young cell biologist MUC genes could influence the recruited to the French National characteristics of mucus gel and, Institute for Agriculture and Food thus, its protective ability. Further, Research (INRA) in the early nine- we discovered that this upregula- ties to study how dietary fibre tion of colonic mucins was impacts human health, I rapidly enhanced when butyrate was the focused my research on these major energy source of the colono- SCFAs, especially on butyrate. The cytes (Gaudier et al., 2004). study of these molecules has revealed local, intermediary, and SCFAs have further effects in the peripheral effects on host tissues, intestine: they also appear to showing how they may influence influence gastrointestinal motility different aspects of host health (Cherbut et al., 1997) in a com- through complex mechanisms. plex manner that has been noted in humans and investigated in Effects in gastrointestinal tract many animal models. The main role of SCFAs is as an Effects on energy metabolism energy source for host colono- cytes through β-oxidation. SCFAs SCFAs provide around 10% of regulate cell proliferation through daily energy for a human host but the release of growth factors or their role in metabolism is not fully gastrointestinal peptides (e.g. understood. These molecules gastrin), or through modulation of appear to have beneficial effects mucosal blood flow (Blottiere et on host energy metabolism, al., 2003). SCFAs are also known to including a role in reducing influence genes that regulate cell plasma concentrations of free proliferation and cell cycle fatty acids (Ge et al., 2008) and (Siavoshian et al., 2000). For cholesterol (Fushimi et al., 2006), example, the transcription factor and/or decreasing plasma glucose AP-1 (activator protein-1) is impli- levels (Sakakibara et al., 2006). cated in cellular proliferation, Work from our laboratory in transformation and death—and in collaboration with the Karolinska 2012 our group demonstrated that Institute in Stockholm had to do GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM 3 EDITORIAL with ANGPTL4 (angiopoietin-like regulatory T cells has been perhaps by altering the intestinal 4), a metabolism-altering protein revealed (Furusawa et al., 2015). environment or by modulating the produced by human intestinal Through their known activation of local immune system in a way that epithelial cells. In an experiment G protein-coupled receptors and reduces cancer risk (Keku et al., with germ-free mice, we found that their influences on the activity of 2015). In the years ahead, more butyrate induced intestinal particular enzymes (namely research is needed on dietary fibre ANGPTL4 gene expression; this lysine/histone deacetylase) and and SCFAs as they relate to CRC occurred with direct oral adminis- transcription factors, SCFAs influ- risk. tration of butyrate, or with coloni- ence the development, survival, zation with the SCFA-producing and function of intestinal epithelial Conclusions bacteria Clostridium tyrobutyricum cells and leukocytes (Corrêa- (Korecka et al., 2013). The molecu- Oliveira et al., 2016). Very recent SCFAs are emerging as important lar mechanisms of how SCFAs work showed that dietary fibre and molecules for host health. SCFA regulate metabolism, however, are SCFAs induced expression of the production is influenced by food not fully understood, and despite RALDH1 enzyme (a vitamin A intake and diet-induced changes in the observation that SCFAs may converting enzyme) in intestinal the gut microbiota (Ríos-Covián et ultimately protect against obesity, epithelial cells, and that the al., 2016), leading some to hypoth- they also provide calories that RALDH1 expression levels in small esize that SCFAs constitute a key could contribute to obesity intestinal epithelial cells correlated link between diet, microbiome, and (Morrison & Preston, 2016). with a number of immune cell health. There is still much to learn changes: altered dendritic cell about the extent of SCFAs’ effects Effects on immune system activity, increased regulatory T on the human body, and probably cells, and higher luminal IgA even the brain. By combining In the late nineties, we and others production (Goverse et al., 2017). mechanistic research with well- reported that SCFAs, especially designed clinical studies we will butyrate, display anti- Effects on cancer advance knowledge of human inflammatory effects with poten- SCFA production, uptake, and tial applications to inflammatory Several links exist between SCFAs excretion, and the pathways by bowel disease (Segain et al., and cancer—in particular, colorec- which these affect overall health. 2000). More recently, their role in tal cancer (CRC). SCFAs may play the generation of differentiation of a role in protection against CRC, Dr. Hervé M. Blottière Dr. Hervé M. Blottière is Director of Research at MICALIS Institute, in the French National Institute for Agricultural Research (INRA). He is also Scientific Director at MetagenoPolis. A tumor immunologist by training, his activities include a broad range of research projects related to digestive tract physiology. He developed, together with Joël Doré, a functional metagenomics approach for studying host-microbiota cross-talk, and also set up the robotic platform METAFUN for high throughput screenings. GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM 4 EDITORIAL References Blottiere, H.M. et al., 2003. Molecular Ge, H. et al., 2008. Activation of G AP-1 Response in Human Intestinal analysis of the effect of short-chain Protein-Coupled Receptor 43 in Epithelial Cells F. Blachier, ed. PLoS fatty acids on intestinal cell Adipocytes Leads to Inhibition of ONE, 7(12), p.e52869. Available at: proliferation. Proceedings of the Lipolysis and Suppression of Plasma http://www.ncbi.nlm.nih.gov/pubmed/ Nutrition Society, 62(1), pp.101–106. Free Fatty Acids. Endocrinology, 23300800 [Accessed February 9, Available at: 149(9), pp.4519–4526. Available at: 2017]. http://www.journals.cambridge.org/abs http://www.ncbi.nlm.nih.gov/pubmed/1 tract_S002966510300017X [Accessed 8499755 [Accessed February 13, 2017]. Ríos-Covián, D. et al., 2016. Intestinal February 10, 2017]. Short Chain Fatty Acids and their Link Goverse, G. et al., 2017. Diet-Derived with Diet and Human Health. Frontiers Cherbut, C. et al., 1997. Effects of Short Chain Fatty Acids Stimulate in microbiology, 7, p.185. Available at: Short-Chain Fatty Acids on Intestinal Epithelial Cells To Induce http://www.ncbi.nlm.nih.gov/pubmed/ Gastrointestinal Motility. Scandinavian Mucosal Tolerogenic Dendritic Cells. 26925050 [Accessed February 12, Journal of Gastroenterology, The Journal of Immunology. 2017]. 32(sup222), pp.58–61. Available at: http://www.ncbi.nlm.nih.gov/pubmed/ Keku, T.O. et al., 2015. The Sakakibara, S. et al., 2006. Acetic acid 9145449 [Accessed February 12, 2017]. gastrointestinal microbiota and activates hepatic AMPK and reduces colorectal cancer. American journal of hyperglycemia in diabetic KK-A(y) Corrêa-Oliveira, R. et al., 2016. physiology. Gastrointestinal and liver mice. Biochemical and Biophysical Regulation of immune cell function by physiology, 308(5), pp.G351-63. Research Communications, 344(2), short-chain fatty acids. Clinical & Available at: pp.597–604. translational immunology, 5(4), p.e73. http://www.ncbi.nlm.nih.gov/pubmed/ Available at: 25540232 [Accessed February 13, Segain JP, et al., 2000. Butyrate http://www.ncbi.nlm.nih.gov/pubmed/2 2017]. inhibits inflammatory responses 7195116 [Accessed February 10, 2017]. through NF-κB inhibition: implications Korecka, A. et al., 2013. ANGPTL4 for Crohn’s disease. Gut, 47:397-403. Furusawa Y, Obata Y, Hase K. (2015). expression induced by butyrate and Commensal microbiota regulates T rosiglitazone in human intestinal Siavoshian S, et al., 2000. Butyrate cell fate decision in the gut. Semin epithelial cells utilizes independent
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