196 Mucosal lactic acid-producing bacteria positively correlate with nutrient uptake and solute transport In the first significant pair of correlated components (component pair 1, P=5.72x10-14, FDR<0.05), the bacterial component is represented by bacteria from order Lactobacillales, family Streptococcaceae, class Bacilli and genus Streptococcus and, to a lesser extent, genus Veillonella, family Christensenallaceae and the Lachnospiraceae NK4A136 group (Supplementary Tables S7-S8). This bacterial component is mainly represented by lactic acid-producing bacteria (LABs, including Lactobacillales, Bacilli, Streptococcaceae, Streptococcus) that actively participate in physiological food digestion, particularly carbohydrate fermentation, with lactic acid being their main metabolic product. Many of these bacterial groups are associated with genes involved in pathways related to solute transport and liver metabolism, including SLC-mediated transmembrane transport of bile salts, organic acids, metal ions and amine compounds; amino acid transport; biological oxidation; cytochrome P450 enzymes and the ephrin signaling pathway (involved in the migration of intestinal epithelial cells along the crypt-villus axis). LABs are widely present in commercially available probiotics, and their beneficial effects on intestinal epithelial health are well-recognized.23 SLC transporters mediate the bidirectional passage of nutrients such as sugars, amino acids, vitamins, electrolytes and drugs across the intestinal epithelium.24 Although SLC transporters are often found to be dysregulated in patients with IBD (particularly CD), their expression may be stimulated and subsequently restored by commensal probiotic bacteria.25-27 Taken together, however, we foresee that this host–microbe interaction component might not be IBD-specific as the genes and bacteria involved have important physiological functions in nutrient digestion and absorption. Mucosa-residing Bifidobacterium species show significant interplay with host fatty acid metabolism and bile acid transport pathways The secondpair of significantly associated components (component pair 3, P=1.89x10-8, FDR<0.05) is predominantly represented by bifidobacteria (Supplementary Tables S9-S10). The top associated pathways are represented by genes involved in fatty acid metabolism, including fatty acid biosynthesis (e.g. ACOT4 and ACSF2), arachidonic acid metabolism (e.g. CYP2J2 and EPHX2) and genes involved in peroxisomal protein import and fatty acid synthesis (e.g. PEX5 and ACOT4), and these genes are all inversely associated with the bacterial component. In contrast, the genes AHR (encoding for the aryl hydrocarbon receptor) and ABCC1 (encoding multidrug resistance protein 1) are positively correlated with the bacterial component. The inverse associations between bifidobacteria and the expression of genes involved in adipogenesis are consistent with findings from animal and small-scale human studies that investigated the effects of treatment with Bifidobacterium species on fatty acid metabolism.28-32 Our findings may reflect the antiinflammatory and anti-lipogenic role of bifidobacteria, which has previously been demonstrated in experimental settings, and may support the therapeutic potential of microbiome-directed interventions in attenuating or preventing colitis.31,32 Chapter 6
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