“This study confirms the gut–sleep–brain axis’s role in sleep disorder and depression, demonstrating that circadian misalignment drives gut dysbiosis, impairing sleep architecture and exacerbating depression and anxiety,” wrote researchers from West Bengal State University and other institutions in India and Saudi Arabia.
The researchers observed that depressive symptoms were linked to lower levels of short-chain fatty acids (SCFAs). They also confirmed the predictive value of microbial metabolites as markers of mental health outcomes, observing that higher levels of tryptophan derivatives such as kynurenine were linked to anxiety.
“Microbial byproducts, such as short-chain fatty acids and tryptophan metabolites, are now seen as key messengers in this gut–sleep–brain dialogue, influencing everything from mood to stress resilience,” they wrote, noting the potential for probiotic applications in the treatment of mental illness.
“What is particularly interesting is that this relationship goes both ways: not only does the biological clock influence gut health, but the gut microbiota also appears to impact the body’s internal timing and cognitive functions.”
Study details
The randomized controlled trial involved 99 adults with sleep problems and depression and anxiety symptoms who consumed a daily probiotic containing Lactobacillus rhamnosus GG (10B CFU) and Bifidobacterium longum (5B CFU) or placebo for 12 weeks. The researchers instructed the participants to take the capsules between 7 a.m. and 9 a.m. “to coincide with the body’s natural circadian rhythms—specifically, when gut microbial activity tends to peak.”
Participants also limited their dietary sugar intake to 20 g per day, and a nutritionist monitored compliance.
Researchers tracked the participants’ sleep using overnight studies and wearable devices, assessed depressive symptoms with questionnaires and used stool samples to analyze gut bacteria and their metabolites.
They employed “advanced statistics and machine learning” to pinpoint key microbial factors linked to sleep and mental health.
Analysis determined that participants with depressive symptoms and disrupted sleep had “fewer beneficial gut bacteria like Bifidobacterium and Lactobacillus, more inflammation-related microbes and lower levels of helpful short-chain fatty acids” at the start of the study.
After 12 weeks, the researchers reported a statistically significant increase in beneficial bacteria, improved sleep and greater reductions in depression and anxiety scores in the probiotic group compared to the placebo group.
Pathway analysis showed that “circadian misalignment predicted gut dysbiosis,” which was linked to sleep disorders and mental health problems. Probiotics treatment enhanced microbial balance and circadian alignment.
“Increases in SCFA-producing bacteria most strongly predicted improvements,” the researchers wrote.
Additionally, the machine learning used assess the predictive value of microbial metabolites as markers of depression and anxiety revealed that butyrate and kynurenine serve as reliable biomarkers, making them potentially useful in precision psychiatry.
The researchers called for further studies to explore “circadian-aligned dietary interventions, alongside probiotics, in larger, more diverse populations.”
Source: Brain Sciences. 2025, 15(7), 761. doi: 10.3390/brainsci15070761. “Effects of Probiotic Supplementation on Depressive Symptoms, Sleep Quality, and Modulation of Gut Microbiota and Inflammatory Biomarkers: A Randomized Controlled Trial.” Authors: S. Rehan Ahmad et al.