Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system

Ala, Moein

doi:10.1080/08830185.2021.1954638

Cited by 64 publications

(52 citation statements)

References 172 publications

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“…Although it has been already shown in humans as well as in dogs that intestinal dysbiosis is related to reductions in tryptophan–indole pathways [ 6 , 82 ], our study found that age had an effect on faeces content of indole, which resulted to be higher in animals as old as 5 years (mean age of dogs completing the study: 5.1 ± 1.8 years; 3–8). This finding is not unprecedented: a human study described an inverse relationship between faecal indole synthesis and ageing, as a consequence of a progressive reduction in the expression of two gut microbial enzymes involved in tryptophan-to-indole metabolism (i.e., tryptophanase and tryptophan synthase) [ 83 ].…”

Section: Discussioncontrasting

confidence: 69%

The Use of Ascophyllum nodosum and Bacillus subtilis C-3102 in the Management of Canine Chronic Inflammatory Enteropathy: A Pilot Study

Isidori

Rueca

Massacci

et al. 2021

Animals

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The aim was to assess the effects of Ascophyllum nodosum (AN) with/without Bacillus subtilis C-3102 as alternative treatments for Chronic Inflammatory Enteropathy (CIE) of dogs. Fourteen CIE patients, which had received the same control (CTR) diet, were enrolled to serially receive three diets: (1) hydrolysed protein (HP) diet; (2) 4.0% AN supplemented HP (HPA) food, (3) HPA diet fortified with 125 billion B. subtilis C-3102 spores/10 kg body weight (HPAB diet). Clinical outcome was assessed by Canine Inflammatory Bowel Disease Activity Index (CIBDAI), whereas gut microbiota compositional variations were investigated via 16S rRNA gene analysis, and faecal fermentation end-products by liquid chromatography. Higher abundances of the Ruminococcaceae and Rikenellaceae families were shown in HPA relative to CTR treatment, with Bacillus genus being differentially abundant on HPAB diet. Concentrations of acetate were higher (p < 0.05) in dogs fed HPA compared to CTR diet, and amounts of isovalerate and isobutyrate were greater (p < 0.05) in HPA compared to HP food. A tendency for higher amounts of faecal butyrate was found for the HPAB treatment (p = 0.06). Comprehensively, while displaying potentially positive effects on faecal fermentations, the tested substances failed to improve CIBDAI scores and microbial richness in CIE dogs.

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Section: Discussioncontrasting

confidence: 69%

The Use of Ascophyllum nodosum and Bacillus subtilis C-3102 in the Management of Canine Chronic Inflammatory Enteropathy: A Pilot Study

Isidori

Rueca

Massacci

et al. 2021

Animals

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show abstract

“…Its activity affects several physiological and pathological processes, including carcinogenesis [32]. It is widely accepted that AHR is involved in IBD, and this idea is consistently presented in topical reviews on the subject [33][34][35][36][37]. In the intestine, an anti-inflammatory and regenerative outcome of AHR activation was reported.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets

Wnorowski

Wnorowska

Kurzepa

et al. 2021

IJMS

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A meta-analysis of publicly available transcriptomic datasets was performed to identify metabolic pathways profoundly implicated in the progression and treatment of inflammatory bowel disease (IBD). The analysis revealed that genes involved in tryptophan (Trp) metabolism are upregulated in Crohn’s disease (CD) and ulcerative colitis (UC) and return to baseline after successful treatment with infliximab. Microarray and mRNAseq profiles from multiple experiments confirmed that enzymes responsible for Trp degradation via the kynurenine pathway (IDO1, KYNU, IL4I1, KMO, and TDO2), receptor of Trp metabolites (HCAR3), and enzymes catalyzing NAD+ turnover (NAMPT, NNMT, PARP9, CD38) were synchronously coregulated in IBD, but not in intestinal malignancies. The modeling of Trp metabolite fluxes in IBD indicated that changes in gene expression shifted intestinal Trp metabolism from the synthesis of 5-hydroxytryptamine (5HT, serotonin) towards the kynurenine pathway. Based on pathway modeling, this manifested in a decline in mucosal Trp and elevated kynurenine (Kyn) levels, and fueled the production of downstream metabolites, including quinolinate, a substrate for de novo NAD+ synthesis. Interestingly, IBD-dependent alterations in Trp metabolites were normalized in infliximab responders, but not in non-responders. Transcriptomic reconstruction of the NAD+ pathway revealed an increased salvage biosynthesis and utilization of NAD+ in IBD, which normalized in patients successfully treated with infliximab. Treatment-related changes in NAD+ levels correlated with shifts in nicotinamide N-methyltransferase (NNMT) expression. This enzyme helps to maintain a high level of NAD+-dependent proinflammatory signaling by removing excess inhibitory nicotinamide (Nam) from the system. Our analysis highlights the prevalent deregulation of kynurenine and NAD+ biosynthetic pathways in IBD and gives new impetus for conducting an in-depth examination of uncovered phenomena in clinical studies.

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“…Trp can be directly utilized by E. coli, Firmicutes Clostridium sporogenes, Ruminococcus gnavus, Lactobacillus, Clostridium, Bacteroides, and others to produce indole, indican, tryptamine, and skatole as well as indole acid derivatives (118). Increased Trp metabolism has been linked to the occurrence of CRC and inflammatory bowel disease (119,120). Previous research has found a decreased indole to Trp ratio in CRC patients when compared to healthy controls (121).…”

Section: Tryptophan (Trp) Metabolitesmentioning

confidence: 99%

“…This change in the indolic pathway may result in an increased inflammatory response in colon carcinogenesis, impacting aryl hydrocarbon receptor (AhR) signaling (118). The AhR activated by bacterial Trp metabolites releasing the secretion of cytokines like IL-22, IL-6, IL10, PTGS2, VEGFA, CYP1A1 and reducing pro-inflammatory cytokines like IL-17 could regulate the release of mucus proteins such as Mucin 2 and antimicrobial peptides in intestinal epithelial cells so that maintain gut immune, inflammation and barrier functions (118,119,(121)(122)(123)(124). Furthermore, bacterial Trp metabolites are also ligands for PXR.…”

Section: Tryptophan (Trp) Metabolitesmentioning

confidence: 99%

Alterations in the Gut Microbiota and Their Metabolites in Colorectal Cancer: Recent Progress and Future Prospects

Zhang

et al. 2022

Front. Oncol.

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Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The etiology and pathogenesis of CRC remain unclear. A growing body of evidence suggests dysbiosis of gut bacteria can contribute to the occurrence and development of CRC by generating harmful metabolites and changing host physiological processes. Metabolomics, a systems biology method, will systematically study the changes in metabolites in the physiological processes of the body, eventually playing a significant role in the detection of metabolic biomarkers and improving disease diagnosis and treatment. Metabolomics, in particular, has been highly beneficial in tracking microbially derived metabolites, which has substantially advanced our comprehension of host-microbiota metabolic interactions in CRC. This paper has briefly compiled recent research progress of the alterations of intestinal flora and its metabolites associated with CRC and the application of association analysis of metabolomics and gut microbiome in the diagnosis, prevention, and treatment of CRC; furthermore, we discuss the prospects for the problems and development direction of this association analysis in the study of CRC. Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.

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Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system

Cited by 64 publications

References 172 publications

The Use of Ascophyllum nodosum and Bacillus subtilis C-3102 in the Management of Canine Chronic Inflammatory Enteropathy: A Pilot Study

The Use of Ascophyllum nodosum and Bacillus subtilis C-3102 in the Management of Canine Chronic Inflammatory Enteropathy: A Pilot Study

Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets

Alterations in the Gut Microbiota and Their Metabolites in Colorectal Cancer: Recent Progress and Future Prospects

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