The gut microbiota at the intersection of diet and human health

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Abstract

Diet affects multiple facets of human health and is inextricably linked to chronic metabolic conditions such as obesity, type 2 diabetes, and cardiovascular disease. Dietary nutrients are essential not only for human health but also for the health and survival of the trillions of microbes that reside within the human intestines. Diet is a key component of the relationship between humans and their microbial residents; gut microbes use ingested nutrients for fundamental biological processes, and the metabolic outputs of those processes may have important impacts on human physiology. Studies in humans and animal models are beginning to unravel the underpinnings of this relationship, and increasing evidence suggests that it may underlie some of the broader effects of diet on human health and disease.

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Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids

Patricia Ojeda, Mark W. Musch, Saskia Urlass … (2018)

The gut microbiota play important roles in lipid metabolism and absorption. However, the contribution of the small bowel microbiota of mammals to these diet-microbe interactions remains unclear. We determine that germ-free (GF) mice are resistant to diet-induced obesity and malabsorb fat with specifically impaired lipid digestion and absorption within the small intestine. Small bowel microbes are essential for host adaptation to dietary lipid changes by regulating gut epithelial processes involved in their digestion and absorption. Additionally, GF mice conventionalized with high-fat diet-induced jejunal microbiota, exhibit increased lipid absorption even when fed a low-fat diet. Conditioned media from specific bacterial strains directly upregulates lipid absorption genes in murine proximal small intestinal epithelial organoids. These findings indicate that proximal gut microbiota play key roles in host adaptability to dietary lipid variations through mechanisms involving both the digestive and absorptive phases and that these functions may contribute to conditions of over- and undernutrition. Martinez-Guryn et al. demonstrate that small intestinal microbiota are critical transducers of dietary signals that allow the host to adapt to variations in lipid digestion and absorption. High fat diet-induced jejunal microbiota directly promote mucosal lipid absorption, and are potentially a factor contributing to conditions of over- and undernutrition.

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Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon.

Markus Waldecker, Tanja Kautenburger, Heike Daumann … (2008)

Colorectal cancer is the most abundant cause of cancer mortality in the Western world. Nutrition and the microbial flora are considered to have a marked influence on the risk of colorectal cancer, the formation of butyrate and other short-chain fatty acids (SCFAs) possibly playing a major role as chemopreventive products of microbial fermentation in the colon. In this study, we investigated the effects of butyrate, other SCFAs, and of a number of phenolic SCFA and trans-cinnamic acid derivatives formed during the intestinal degradation of polyphenolic constituents of fruits and vegetables on global histone deacetylase (HDAC) activity in nuclear extracts from colon carcinoma cell cultures using tert-butoxycarbonyl-lysine (acetylated)-4-amino-7-methylcoumarin (Boc-Lys(Ac)-AMC) as substrate. Inhibition of HDAC activity, e.g., by butyrate, is related to a suppression of malignant transformation and a stimulation of apoptosis of precancerous colonic cells. In nuclear extracts from HT-29 human colon carcinoma cells, butyrate was found to be the most potent HDAC inhibitor (IC50=0.09 mM), while other SCFAs such as propionate were less potent. In the same assay, p-coumaric acid (IC50=0.19 mM), 3-(4-OH-phenyl)-propionate (IC50=0.62 mM) and caffeic acid (IC50=0.85 mM) were the most potent HDAC inhibitors among the polyphenol metabolites tested. Interestingly, butyrate was also the most potent HDAC inhibitor in a whole-cell HeLa Mad 38-based reporter gene assay, while all polyphenol metabolites and all other SCFAs tested were much less potent; some were completely inactive. The findings suggest that butyrate plays an outstanding role as endogenous HDAC inhibitor in the colon, and that other SCFAs and HDAC-inhibitory polyphenol metabolites present in the colon seem to play a much smaller role, probably because of their limited levels, their marked cytotoxicity and/or their limited intracellular availability.

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Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages

Smitha Krishnan, Yufang Ding, Nima Saedi … (2018)

SUMMARY The gut microbiota plays a significant role in the progression of fatty liver disease; however, the mediators and their mechanisms remain to be elucidated. Comparing metabolite profile differences between germ-free and conventionally raised mice against differences between mice fed a low- and high-fat diet (HFD), we identified tryptamine and indole-3-acetate (I3A) as metabolites that depend on the microbiota and are depleted under a HFD. Both metabolites reduced fatty-acid- and LPS-stimulated production of pro-inflammatory cytokines in macrophages and inhibited the migration of cells toward a chemokine, with I3A exhibiting greater potency. In hepatocytes, I3A attenuated inflammatory responses under lipid loading and reduced the expression of fatty acid synthase and sterol regulatory element-binding protein-1c. These effects were abrogated in the presence of an aryl-hydrocarbon receptor (AhR) antagonist, indicating that the effects are AhR dependent. Our results suggest that gut microbiota could influence inflammatory responses in the liver through metabolites engaging host receptors.

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Journal

Title: Science

Abbreviated Title: Science

Publisher: American Association for the Advancement of Science (AAAS)

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date Created: November 15 2018

Publication date Created: November 16 2018

Publication date (Electronic): November 15 2018

Publication date (Print): November 16 2018

Volume: 362

Issue: 6416

Pages: 776-780

Article

DOI: 10.1126/science.aau5812

PubMed ID: 30442802

SO-VID: 55e31005-1fa6-45d5-90f2-898f365ff7ba

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The gut microbiota at the intersection of diet and human health

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Most cited references 32

Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids

Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon.

Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages

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Cited by 387

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