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Lactobacillus reuteri tryptophan metabolism promotes host susceptibility to CNS autoimmunity, 2022, Theresa L. Montgomery et al

Discussion in 'Other health news and research' started by Mij, Nov 25, 2022.

  1. Mij

    Mij Senior Member (Voting Rights)

    Messages:
    8,314
    Abstract
    Background
    Dysregulation of gut microbiota-associated tryptophan metabolism has been observed in patients with multiple sclerosis. However, defining direct mechanistic links between this apparent metabolic rewiring and individual constituents of the gut microbiota remains challenging. We and others have previously shown that colonization with the gut commensal and putative probiotic species, Lactobacillus reuteri, unexpectedly enhances host susceptibility to experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. To identify underlying mechanisms, we characterized the genome of commensal L. reuteri isolates, coupled with in vitro and in vivo metabolomic profiling, modulation of dietary substrates, and gut microbiota manipulation.

    Results
    The enzymes necessary to metabolize dietary tryptophan into immunomodulatory indole derivatives were enriched in the L. reuteri genomes, including araT, fldH, and amiE. Moreover, metabolite profiling of L. reuteri monocultures and serum of L. reuteri-colonized mice revealed a depletion of kynurenines and production of a wide array of known and novel tryptophan-derived aryl hydrocarbon receptor (AhR) agonists and antagonists, including indole acetate, indole-3-glyoxylic acid, tryptamine, p-cresol, and diverse imidazole derivatives. Functionally, dietary tryptophan was required for L. reuteri-dependent EAE exacerbation, while depletion of dietary tryptophan suppressed disease activity and inflammatory T cell responses in the CNS. Mechanistically, L. reuteri tryptophan-derived metabolites activated the AhR and enhanced T cell production of IL-17.

    Conclusions
    Our data suggests that tryptophan metabolism by gut commensals, such as the putative probiotic species L. reuteri, can unexpectedly enhance autoimmunity, inducing broad shifts in the metabolome and immunological repertoire.

    https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01408-7
     
    AnneM, Amw66, Peter Trewhitt and 2 others like this.
  2. Samuel

    Samuel Senior Member (Voting Rights)

    Messages:
    626
    l reuteri is in at least one supplement. there is an mepedia page.
     
    Peter Trewhitt likes this.
  3. BrightCandle

    BrightCandle Senior Member (Voting Rights)

    Messages:
    338
    BioGaia is the name of the company that does a human variant of this bacteria. Its quite expensive so if you want to try introducing it I suggest making yoghurt from it, it processes lactose and 42C is about optimal for this bacteria.

    Its quite an interesting bacteria in general because it was found in all indigenous people around the world and yet only about 2% of urban humans have it. It actually sits higher up in the small intestine mostly and excretes an anti bacterial and anti fungal that keeps the small intestine clear. As far as I know there hasn't been much good to say on whether taking in the probiotic is beneficial and recolonises the gut. I have taken it and I have taken it in yoghurt format and it was a complete non event for me (the yoghurt is fairly OK). It looks like its a very important species its one of the stand outs of what modern medicine seems to have accidentally killed off with antibiotics or the polluted environment or something else.

    PS If anyone wants some instructions on how to convert these probiotics into a yoghurt do let me know and I'll make a post about it.
     
    Last edited: Nov 26, 2022
    Peter Trewhitt and Trish like this.

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