Gut microbiota-derived metabolites as key actors in inflammatory bowel disease

Abstract

A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.

Ethanolamine improves colonic barrier functions and inflammatory immunoreactions via shifting microbiome dysbiosis

“…Significant variations between the control group and the low EA treated group were identified, and Oxidative phosphorylation, Lipopolysaccharide biosynthesis, Arginine and proline metabolism, Folate biosynthesis and Biotin metabolism were more abundant in the low EA treated group. These metabolic changes are coincident with studies that reported beneficial impacts of dietary fiber intervention in IBD 3,34 . These results may indicate that EA could shift the composition and metabolic functions of colonic microbiota to restore microbial dysbiosis.…”

“…Nutrient signals, microbiome dysbiosis, and host immunoreactions have a pivotal role in the development of inflammatory bowel diseases (IBD) and colorectal cancer [1][2][3][4] . The gastrointestinal tract not only acts as the primary site of food digestion and nutrition absorption but also provides an essential interface for the interactions of gut microbiota and immune systems 5 .…”

“…The gastrointestinal tract not only acts as the primary site of food digestion and nutrition absorption but also provides an essential interface for the interactions of gut microbiota and immune systems 5 . Dramatic alterations in the composition of gut microbiota and intestinal barrier dysfunction have been found in IBD Patients 3,6 .Nutrient signals including gut microbial-derived metabolites, aromatic amino acids, short-chain fatty acids and activate compounds can directly impact the establishment of the tumor-associated microenvironment and contribute to host-microbial interactions in the progress of the colorectal cancer [3][4] . Extensive works have demonstrated the roles of L-arginine 7 and tryptophan 8 , and short-chain fatty acids like butyrate 9 and acetate 10 in altering host-microbial interactions to restore gut homeostasis and alleviate intestinal inflammation through diverse mechanisms 3 .…”

“…A recent study highlighted that EA could promote the mesenchymal-to-epithelial transitions via a CDP-EA-Pebp1 dependent manner that ultimately leads to NF-κB inhibition 11 . Ethanolamine has been associated with the pathogenesis of eut pathogens such as Salmonella 16 and enterohemorrhagic Escherichia coli (EHEC) 17 that have been reported to promote colorectal carcinogenesis and tumor formation [2][3] . For instance, several studies have demonstrated that S. Typhimurium can sidestep nutritional competition with commensal bacteria by utilizing EA in inflamed gut 16,[19][20] .…”

A unique and reliable fecal DNA extraction method for 16S rRNA gene and shotgun metagenomic sequencing in the analysis of the human gut microbiome

“…In recent years, advances in next-generation sequencing (NGS) have revolutionized the analysis of complex microbial ecosystems including the gut microbiota, leading to advanced understanding of its role in health and disease [1][2][3][4][5][6]. Alterations in the composition and diversity of the gut microbiota communities have been correlated with a large number of diseases, such as in ammatory bowel disease [7][8][9][10][11], irritable bowel syndrome [12,13], metabolic disorders (e.g, type 2 diabetes (T2D), obesity and nonalcoholic fatty liver disease (NALFD)) [14][15][16][17][18][19], and more recently, cancer [20][21][22][23][24][25][26][27][28][29][30].…”