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Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.

ABSTRACT: Tryptophan modulates disease activity and the composition of microbiota in the B6.Sle1.Sle2.Sle3 (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intestinal inflammation. A bloom of Ruminococcus gnavus (Rg), a bacterium associated with disease flares in lupus patients, only emerged in the recipients of TC microbiota fed with high tryptophan. Rg depletion in TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, TC mice colonized with Rg showed higher autoimmune activation. Overall, these results suggest that the interplay of genetic and tryptophan can influence the pathogenesis of lupus through the gut microbiota.

SUBMITTER: Ma L

PROVIDER: S-EPMC10827173 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.

Ma Longhuan L Ge Yong Y Brown Josephine J Choi Seung-Chul SC Elshikha Ahmed A Kanda Nathalie N Terrell Morgan M Six Natalie N Garcia Abigail A Mohamadzadeh Mansour M Silverman Gregg G Morel Laurence L

bioRxiv : the preprint server for biology 20240119

Tryptophan modulates disease activity and the composition of microbiota in the B6.<i>Sle1.Sle2.Sle3</i> (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intes ...[more]

PMID: 38293097

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Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.

Publications

Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.

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