We are pleased to announce that Prof. Yoshikazu Nakaoka from National Cerebral and Cardiovascular Center Research Institute, Japan will join Second Conjoint RIKEN – ISM 2026 as a speaker and give a presentation entitled “Gut Microbes, Tryptophan Metabolism, and Pulmonary Hypertension: A Targetable Gut–Lung Axis“.

Dietary tryptophan is an essential host nutrient and a substrate for intestinal microbes. Host epithelial absorption limits microbial access, whereas microbial metabolism generates indole derivatives (indoles) that can activate the aryl hydrocarbon receptor (AHR), a regulator of barrier and immune function. Whether disruption of this nutrient partitioning leads to excess pathogenic metabolites and drives disease beyond the gut is unknown. We investigated this question in pulmonary arterial hypertension (PAH), a fatal vascular disease in which AHR activation promotes inflammation and remodeling (Masaki et al., PNAS 2021; Asano et al., under revision). Here we show that PAH is sustained by a self-amplifying intestinal circuit linking gut dysbiosis, impaired tryptophan absorption, and excess production of AHR-activating indoles. In a patient cohort enriched for PAH, ectopic oral bacteria and expansion of bacteria A were associated with increased fecal indoles, intestinal AHR activity, and poor outcomes. Gnotobiotic, pharmacological, and genetic studies have shown that microbiota-derived indoles exacerbate pulmonary vascular remodeling via AHR signaling. Therapeutically, the intestinal adsorbent substance-X interrupted this circuit and attenuated disease. These findings identify intestinal nutrient partitioning as a targetable gut-lung mechanism that converts dysbiosis into distal vascular pathology, namely PAH.

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The 2^nd RIKEN-ISM Conjoint Meeting
Tokyo Microbiota 2026
September 24-25, 2026 – The University of Tokyo, Japan
tokyo.microbiota-ism.com