Improvement of sleep quality and sub-health conditions through pasteurized fermented milk consumption: A human intervention study

• There is no additional benefit of adding prebiotics to pasteurized probiotic fermented milk. • Drinking pasteurized probiotic fermented milk can improve sleep quality and alleviated sub-health symptoms. • The improvement of sub-health symptoms is associated with specific changes in gut microbiota and serum and fecal metabolites. The sub-health state refers to a transitional condition between optimal health and disease, impacting physical, psychological, and social well-being. In this 42-day human intervention trial, we investigated the effects of two pasteurized fermented milks on sub-health symptoms. These pasteurized fermented milks shared the same starter culture and probiotic strains ( Lacticaseibacillus paracasei PC-01, Lactiplantibacillus plantarun Lp-6, Lactobacillus helveticus H9, and Bifidobacterium animalis subsp. lactis Probio-M8), differing only in the presence of inulin. Qualified subjects were randomly assigned to the probiotic group (received milk without inulin; n = 49 or synbiotic group (received milk with inulin; n = 51). Outcome measures included Sub-Health Measurement Scale (SHMS) and Pittsburgh Sleep Quality Index (PSQI) scores, fecal metagenomes, metabolomes, and short-chain fatty acids, and serum neurotransmitter levels at baseline, after a 4-week intervention (day 28), and a 2-week-follow-up period (day 42). Our results showed that both pasteurized fermented milks improved sleep quality and alleviated sub-health symptoms, with no significant added benefit from inulin. Fecal metagenome analysis revealed post-interventional changes in gut microbial composition, including increased Bifidobacterium longum and decreased potentially pro-inflammatory bacteria ( Blautia sp. and Dorea sp.). Changes in Blautia sp. and B. longum correlated significantly with SHMS and PSQI scores, respectively. Fecal and serum metabolite analysis showed post-interventional modulation of fecal short-chain fatty acids, anti-inflammatory bioactive metabolites, and serum neurotransmitters such as gamma-aminobutyric and serotonin hydrochloride. In conclusion, pasteurized fermented milk intake alleviated sub-health symptoms, affected the gut microbiome, metabolome, and serum metabolites. These findings highlight the potential of pasteurized fermented milk for mitigating sub-health conditions.