Gut microbiota-derived metabolites in inflammatory diseases based on targeted metabolomics

Abstract

The gut microbiota plays an important role in inflammatory diseases. Metabolites in the three metabolic pathways of tryptophan (Trp), histidine (His), and phenylalanine (Phe) can affect various inflammatory conditions, such as obesity, diabetes, arthritis, colitis, atherosclerosis, and neuroinflammation. We established an LC–MS/MS method to measure 17 metabolites—Trp, 3-indole-acetic acid (Iaa), 3-indole-lactate (Ila), 3-indole-propionic acid (Ipa), 3-indole formaldehyde (Iald), kynurenine (Kn), kynurenic acid (Kyna), 3-Hydroxyanthranilic acid (3-Haa), His, 3-methylhistidine (3-Mhis), histamine (Hist), imidazole propionic acid (Imp), 4-imidazoacetic acid (Imaa), urocanic acid (Ua), Phe, phenylethylamine (Pea), and hippuric acid (Ha)—in the three metabolic pathways. The method exhibited high sensitivity and good selectivity, linearity, accuracy, precision, stability; and recovery rate; all met the requirements of biological sample analysis. By establishing a rheumatoid arthritis (RA) model of Sprague–Dawley rats and performing 16S rRNA sequencing on their feces, it was found that there was dysbiosis, including changes in phylum level, genus level, and α biodiversity of gut bacteria. The contents of the microbiota metabolites Iaa and Ipa in the model group were significantly decreased, and those of Iald, Kn, Kyna, Ha, and Imp were significantly increased. The common therapeutic drugs Tripterygium glycosides, total glucosides of peony, and their main active ingredients were screened by in vitro incubation with gut bacteria: it was found that Tripterygium glycosides and their active ingredients could lead to a variation in metabolites in the Trp and Phe pathways. Total glucosides and active components of peony could lead to a variation in metabolites in the Phe pathway of the gut microbiota.

Mitochondria as novel mediators linking gut microbiota to atherosclerosis that is ameliorated by herbal medicine: A review

“…Small metabolites are transported into the bloodstream via transcellular or paracellular routes, whereas large metabolites disrupt the gut barrier and are released into the body ( Kirichenko et al, 2020 ). Indole derivatives, such as indoxyl sulfate, indole ethanol, and indole acrylic acid, are produced by the gut microbiota from tryptophan and induce proinflammatory activity after entering the bloodstream ( Xu H et al, 2022 ). In addition, indolepropionic acid (IPA), which is metabolized from tryptophan, is substantially reduced in patients with coronary artery disease.…”

In-vitro digestion models to examine the effects of Plant-Based Meat substitutes on Gut Microbial Metabolites

“…3-MH, as a part of the histidine metabolic pathway, may have a role in inflammation diseases. However, the association was not established in stool on a mice model 53 . An in vivo study analyzing feces has recently found lower amounts of 3-MH and anserine ( see section 3.2.2 ) in patients with irritable bowel syndrome 56 .…”

“…Higher levels of tyrosine (Fig 3, C) and tryptophan (Fig 3, D) were observed in the PP than in the rest of the groups throughout the colonic fermentation. Phenylalanine, tryptophan, and histidine metabolomic pathways are closely related to gut inflammation 53 . In the case of phenylalanine and tryptophan, no relevant derived metabolites were found through the metabolomics pipeline.…”

Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

“…Furhermore, the inflammatory and metabolic pathways are complex networks contextdependent by various factors, including genetics, diet, cell status, and environmental factors (Yang et al, 2022). The mechanism of gut microbiota involvement in the occurrence and development of inflammatory diseases is very complex, and research on how intestinal metabolites and the host interact to affect diseases is a hot topic (Xu et al, 2022a). Further studies are needed to assess the impact of intestinal dysbiosis and gut microbiota-derived metabolites rather than specific bacterial species to understand the mechanisms involved in RA pathogenesis.…”

“…Growing evidence has suggested the role of gut microbiota in the onset of arthritis. Studies in mice (Rosser et al, 2014;Liu et al, 2016;Jubair et al, 2018;Maeda and Takeda, 2019;Peng et al, 2019;Aa et al, 2020), rats (Huang et al, 2019;Peng et al, 2019;Yue et al, 2019;Xu et al, 2020;Xu et al, 2022a), and pigs (Mansson et al, 1971) consistently demonstrate that gut dysbiosis is associated with inflammatory arthritis development.…”