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D-Tryptophan suppresses enteric pathogen and pathobionts and prevents colitis by modulating microbial tryptophan metabolism

ABSTRACT: Summary D-Amino acids (D-AAs) have various functions in mammals and microbes. D-AAs are produced by gut microbiota and can act as potent bactericidal molecules. Thus, D-AAs regulate the ecological niche of the intestine; however, the actual impacts of D-AAs in the gut remain unknown. In this study, we show that D-Tryptophan (D-Trp) inhibits the growth of enteric pathogen and colitogenic pathobionts. The growth of Citrobacter rodentium in vitro is strongly inhibited by D-Trp treatment. Moreover, D-Trp protects mice from lethal C. rodentium infection via reduction of the pathogen. Additionally, D-Trp prevents the development of experimental colitis by the depletion of specific microbes in the intestine. D-Trp increases the intracellular level of indole acrylic acid (IA), a key molecule that determines the susceptibility of enteric microbes to D-Trp. Treatment with IA improves the survival of mice infected with C. rodentium. Hence, D-Trp could act as a gut environmental modulator that regulates intestinal homeostasis. Graphical abstract Highlights • D-Trp inhibits the growth of Citrobacter rodentium in vitro and in vivo• D-Trp suppresses experimental colitis by the depletion of specific gut microbes• IA is the metabolite that determines the susceptibility of enteric microbes to D-Trp Cell biology; Cellular physiology; Microbiology; Microbiome

SUBMITTER: Seki N

PROVIDER: S-EPMC9391578 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Project description:As decentralized water reuse continues to gain popularity, risk-based treatment guidance is increasingly sought for the protection of public health. However, effort s to evaluate pathogen risks and log-reduction requirements have been hindered by an incomplete understanding of pathogen occurrence and densities in locally-collected wastewaters (i.e., from decentralized collection systems). Of particular interest is the potentially high enteric pathogen concentration in small systems with an active infected excreter, but generally lower frequency of pathogen occurrences in smaller systems compared to those with several hundred contributors. Such variability, coupled with low concentrations in many source streams (e.g., sink, shower/bath, and laundry waters), has limited direct measurement of pathogens. This study presents an approach to modeling pathogen concentrations in variously sized greywater and combined wastewater collection systems based on epidemiological pathogen incidence rates, user population size, and fecal loadings to various residential wastewater sources. Pathogen infections were modeled within various population sizes (5-, 100-, and 1,000-person) for seven reference pathogens (viruses: adenoviruses, Norovirus, and Rotavirus; bacteria: Campylobacter and Salmonella spp.; and protozoa: Cryptosporidium and Giardia spp.) on each day of 10,000 possible years, accounting for intermittent infection and overlap of infection periods within the population. Fecal contamination of fresh greywaters from bathroom sinks, showers/baths, and laundry, as well as combined greywater and local combined wastewater (i.e., including toilets), was modeled based on reported fecal indicators in the various sources. Simulated daily infections and models of fecal contamination were coupled with pathogen shedding characteristics to generate distributions of pathogen densities in the various waters. The predicted frequency of pathogen occurrences in local wastewaters was generally low due to low infection incidence within small cohort groups, but increased with collection scale (population size) and infection incidence rate (e.g., Norovirus). When pathogens did occur, a decrease in concentrations from 5- to 100- and from 100- to 1,000-person systems was observed; nonetheless, overall mean concentrations (i.e., including non-occurrences) remained the same due to the increased number of occurrences. This highlights value of the model for characterizing scaling effects over averaging methods, which overestimate the frequency of pathogen occurrence in small systems while underestimating concentration peaks that likely drive risk periods. Results of this work will inform development of risk-based pathogen reduction requirements for decentralized water reuse.

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D-Tryptophan suppresses enteric pathogen and pathobionts and prevents colitis by modulating microbial tryptophan metabolism

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