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New Findings What is the central question of this study?Is there a link between gut microbial fermentation and ventilatory responsiveness to hypoxia in humans? What is the main finding and its importance?Increased gut microbial fermentation is associated with augmented ventilatory (but not haemodynamic) responses to transient hypoxia. These findings imply a capacity for gut microbiota to modulate the peripheral chemoreflex response to hypoxia in humans. Abstract Recent animal data indicate the presence of a bidirectional link between gut microbial activity and respiratory control. Nevertheless, the presence of a similar association between gut microbiota and peripheral chemoreceptor responsiveness to hypoxia in humans has not been reported to date. Therefore, we performed a within subject, placebo‐controlled study in a group of 16 healthy individuals (eight men; mean ± SD age 25.9 ± 5.2 years). Participants underwent two tests (in a random order), receiving lactulose, which stimulates gut fermentation, or placebo. Ventilatory and haemodynamic responses to transient hypoxia were evaluated before and 2 h after the test meal. The magnitude of these responses was related to the net hydrogen content in the exhaled air, reflecting gut fermentation intensity. A lactulose meal, compared to placebo, caused an increase in the minute ventilation (Hyp‐VI; l/min/SnormalpO2) and breathing rate (Hyp‐BR; breaths/min/SnormalpO2) responses to hypoxia (for Hyp‐VI, mean ± SD −0.03 ± 0.059 in placebo test vs. 0.05 ± 0.116 in lactulose test, P = 0.03; for Hyp‐BR, −0.015 ± 0.046 vs. 0.034 ± 0.054, P = 0.01). The magnitude of these responses was positively correlated with the lactulose‐induced hydrogen excretion (for Hyp‐VI, r = 0.62, P = 0.01; for Hyp‐BR, r = 0.73, P = 0.001). Changes in the resting parameters during normoxia did not differ significantly between the tests. Our results demonstrate that the increased gut microbial fermentation is associated with augmented ventilatory (but not haemodynamic) responses to the transient hypoxia, which implies a capacity for gut microbiota to modulate the peripheral chemoreflex in humans.