Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases

Nikolaus, Susanna; Schulte, B; Al-Massad, Natalie; Thieme, Florian; Schulte, Dominik M; Bethge, Johannes; Rehman, Ateequr; Tran, Florian; Aden, Konrad; Häsler, Robert; Moll, Natalie; Schütze, Gregor; Schwarz, Markus J.; Waetzig, Georg H.; Rosenstiel, Philip; Krawczak, Michael; Szymczak, Silke; Schreiber, Stefan

doi:10.1053/j.gastro.2017.08.028

Cited by 428 publications

(355 citation statements)

References 35 publications

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“…Studies have also shown an association between serum tryptophan concentrations and disease activity in humans with IBD . Although our study did not document an association between CCEAI or outcome and serum tryptophan concentrations in PLE dogs, there was a significant correlation with serum albumin concentrations.…”

Section: Discussioncontrasting

confidence: 90%

“…Humans with ulcerative colitis, a type of IBD, have decreased serum concentrations of glutamic acid, glutamine, methionine, tryptophan and histidine compared with healthy controls . Similarly, other studies have confirmed low serum tryptophan concentrations in humans with IBD . There is an anti‐inflammatory effect of dietary intervention with tryptophan or tryptophan metabolites in experimental models of colitis, with supplementation ameliorating clinical signs, improving weight gain and histological scores and decreasing gut permeability and expression of pro‐inflammatory cytokines .…”

Section: Introductionmentioning

confidence: 72%

“…There are altered serum amino acid concentrations in humans and animal models of IBD . After 7 days of dextran sodium sulfate (DSS) induced colitis, mice had decreased concentrations of tryptophan, glutamic acid and aspartic acid .…”

Section: Introductionmentioning

confidence: 99%

“…8 Similarly, other studies have confirmed low serum tryptophan concentrations in humans with IBD. 5,9,10 There is an anti-inflammatory effect of dietary intervention with tryptophan or tryptophan metabolites in experimental models of colitis, with supplementation ameliorating clinical signs, improving weight gain and histological scores and decreasing gut permeability and expression of proinflammatory cytokines. 11,12 Similarly, supplementation with glutamine, arginine, N-acetylcysteine, and glycine in animal models of IBD has beneficial effects such as reduced intestinal permeability and decreased production of proinflammatory cytokines.…”

mentioning

confidence: 99%

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Alterations in serum amino acid concentrations in dogs with protein‐losing enteropathy

Kathrani

Allenspach

Fascetti

et al. 2018

Veterinary Internal Medicne

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BackgroundCertain amino acids are decreased in humans with inflammatory bowel disease (IBD) and supplementation with the same amino acids has shown beneficial effects in animal models of IBD. Currently, the amino acid status of dogs with protein‐losing enteropathy (PLE) is unknown.Hypothesis/ObjectiveTo determine if serum amino acid concentrations are abnormal in dogs with PLE and correlated with clinical and laboratory variables and outcome.AnimalsThirty client‐owned dogs diagnosed with PLE and 12 apparently healthy dogs seen at Bristol Veterinary School.MethodsRetrospective study using stored residual serum from fasted dogs with PLE, collected at the time of diagnostic investigation and from apparently healthy dogs. Serum was analyzed for 30 amino acids using an automated high‐performance liquid chromatography amino acid analyzer.ResultsSerum tryptophan concentrations were significantly decreased in dogs with PLE (median, 22 nmol/mL; range, 1–80 nmol/mL) compared with apparently healthy control dogs (median, 77.5 nmol/mL; range, 42–135 nmol/mL, P < .001). There were no significant differences in the remaining 29 serum amino acids between dogs with PLE and apparently healthy. Serum tryptophan concentrations were also significantly correlated with serum albumin concentrations in dogs with PLE (P = .001, R 2 = 0.506).Conclusions and Clinical ImportanceDecreased serum tryptophan concentration might play a role in the pathogenesis of canine PLE or be a consequence of the disease.

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Section: Discussioncontrasting

confidence: 90%

Section: Introductionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Alterations in serum amino acid concentrations in dogs with protein‐losing enteropathy

Kathrani

Allenspach

Fascetti

et al. 2018

Veterinary Internal Medicne

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“…Diet has a profound impact on the microbial profile 34 , 35 . The impact on short chain fatty acid production may be particularly important in shaping disease expression.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

The gut microbiota: cause and cure of gut diseases

White

Bogaerde

Kamm

2018

Medical Journal of Australia

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Summary The gastrointestinal microbiota is emerging as a central factor in the pathogenesis of a range of gastrointestinal and hepatic disorders. Epidemiological studies, and experimental studies in animals and humans, have highlighted a likely causative role of this microbial community in the modern global epidemics of inflammatory bowel disease, non‐alcoholic fatty liver disease, non‐alcoholic steato‐hepatitis, obesity and metabolic syndrome. New techniques for microbial culture and gene sequencing are enabling the identification of specific pathogens and protective organisms in these conditions. Factors that change the microbiota are being defined: dietary pattern, specific foods, food additives in processed food and drinks, such as emulsifiers and non‐sugar sweeteners, and antibiotics. Microbiota changes in early life appear critical to the later development of a range of inflammatory disorders. For many of these conditions, the treatment paradigm will change, at least in part, from immune suppression and drug therapy to treatments that reshape the microbiota or restore its integrity. These treatments include dietary changes, specific microbial manipulation and faecal microbiota transplantation. A dialogue is needed regarding population strategies that target disease prevention. This will include how food is produced, what additives it contains, and how it is processed. Widespread use of antibiotics, from agricultural and veterinary to medicinal settings, needs more attention. At the individual level, microbial profiles may be able to predict who is at risk of disease when subjected to particular environmental influences, and what microbial restoration is needed to minimise risk.

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Categorization of the effects of E. coliLF82 and mutants lacking the chuT and shuU genes on survival, the transcriptome, and metabolome in germ‐free honeybee

Feng,

Zhang,

et al. 2024

FEBS Open Bio

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The precise etiology of inflammatory bowel diseases (IBDs) remains elusive. The Escherichia coli strain LF82 (LF82) is known to be associated with IBD, and we hypothesized that this association may be related to the chuT and shuU genes. Here we constructed a germ‐free (GF) honeybee model to investigate the effects of LF82 chuT and shuU genes on the honeybee intestine and their mechanisms. The chuT and shuU gene deletion strains LF82∆chuT and LF82∆shuU were generated by CRISPR‐Cas9. These strains, together with nonpathogenic E. coli MG1655 (MG1655) and wildtype LF82, were allowed to colonize the guts of GF honeybees to establish single bacterial colonization models. Intestinal permeability was assessed following the administration of a sterile Brilliant Blue (FCF) solution. Comprehensive transcriptomic and metabolomic analyses of intestinal samples indicated that MG1655 had few disadvantageous effects on honeybees. Conversely, colonization with LF82 and its gene‐deletion mutants provoked pronounced activation of genes associated with innate immune pathways, stimulated defensive responses, and induced expression of genes associated with inflammation, oxidative stress, and glycosaminoglycan degradation. Crucially, the LF82∆chuT and LF82∆shuU strains perturbed host heme and iron regulation, as well as tryptophan metabolism. These findings suggest that the deletion of chuT and shuU genes in E. coli LF82 may alleviate intestinal inflammation by partially modulating tryptophan catabolism. Our study proposes that targeting iron uptake mechanisms could be a potential strategy to mitigate the virulence of IBD‐associated bacteria.

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Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases

Cited by 428 publications

References 35 publications

Alterations in serum amino acid concentrations in dogs with protein‐losing enteropathy

Alterations in serum amino acid concentrations in dogs with protein‐losing enteropathy

The gut microbiota: cause and cure of gut diseases

Categorization of the effects of E. coliLF82 and mutants lacking the chuT and shuU genes on survival, the transcriptome, and metabolome in germ‐free honeybee

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