Hormonal
Inhibition of the host enzyme indoleamine 2,3-dioxygenase 1 (IDO1) improves metabolic health by shifting tryptophan metabolism toward gut microbiota-derived indole metabolites, which restore intestinal barrier integrity and reduce systemic inflammation.
To support metabolic health, prioritize dietary patterns that foster a diverse gut microbiome capable of converting dietary tryptophan into protective indole metabolites. This involves consuming sufficient fiber and diverse plant sources. Emerging research suggests that inhibiting the host enzyme IDO1 (which is upregulated in obesity) allows the microbiota to produce more of these beneficial indoles, thereby improving insulin sensitivity and reducing inflammation. While direct IDO1 inhibitors are not yet standard care, supporting the microbiome's ability to perform this conversion is a key mechanistic target.
We recently showed that IDO1 deletion or inhibition in the context of MetS improved insulin sensitivity, decreased endotoxemia, and chronic inflammation, and positively regulated lipid metabolism in liver, and adipose tissues. We found that these beneficial effects were due to rewiring of Trp metabolism toward a microbiota-dependent production of IL-22...
Why this rating
The paper is a mini-review summarizing multiple studies, including mouse models and human observational data, but lacks a single large-scale randomized controlled trial for the specific intervention of IDO inhibition in humans.
Source
Tryptophan Dietary Impacts Gut Barrier and Metabolic Diseases
Soraya Taleb · Frontiers in Immunology · 2019
DOI 10.3389/fimmu.2019.02113
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