The study, conducted by researchers in China, investigated K56’s effects on chronic stress and mental health outcomes among 120 volunteers (18–35 years) recruited from various universities, aiming to offer stress management strategies.
Results found positive effects associated with the intake of the probiotic strain, which the researchers suggest could be attributed to K56-induced changes in microbial composition and butanoate metabolism.
“Our study demonstrates that a two-week intervention with L. paracasei K56 may potentially alleviate stress and significantly ameliorate associated symptoms,” the researchers wrote in the journal Frontiers in Nutrition.
“These findings offer valuable insights into the potential application of short-term psychobiological interventions for stress management in specific populations.”
Probiotics and mental health
In recent years, mental health issues among master’s and doctoral students have reportedly worsened, with one meta-analysis revealing that about 17% of doctoral students experience anxiety, and 24% suffer from depression.
Another global survey of 6,300 graduate students found that 36% of doctoral students sought help for anxiety or depression linked to academic pressures, with thesis writing and defense being major stressors.
The gut microbiota is now known to significantly influence mental health and cognitive function through the gut-brain axis.
Probiotics have been found to enhance gut, brain and mental health by modulating gut microbiota and regulating the gut-brain axis.
L. paracasei K56, a novel probiotic strain from the gastrointestinal tract of healthy infants in China, has previously shown promise in modulating gut microbiota and reducing inflammation in animal studies.
The researchers on the new study hypothesized that K56 may alleviate stress by regulating the gut-brain axis and improving inflammatory immune responses.
L. paracasei K56 may reduce stress, anxiety and insomnia
The randomized, double-blind, placebo-controlled clinical trial with two parallel arms involved a two-week run-in period where participants avoided probiotics and prebiotics, followed by a two-week intervention phase. They received either a daily fermented milk beverage containing L. paracasei K56 (6 × 10^10 CFU live cells per 100 mL) or a placebo.
Participants submitted fecal samples before the study and at weeks one and two and completed weekly online questionnaires assessing stress, anxiety, depression, sleep quality, fatigue and gastrointestinal symptoms.
Results showed that compared to the placebo group, K56 intervention reduced perceived stress scores (DASS), alleviated anxiety and insomnia symptoms, and significantly increased serum 5-HT levels.
The researchers suggest that the effects may stem from modulating beneficial gut bacteria and specific metabolites like butyric acid.
They noted that probiotics offer a promising approach to improving mood and well-being, however, probiotic effects are strain-specific.
While K56 reduced DASS stress scores, it had no significant impact on perceived stress scores (PSS) scores, aligning with similar studies and reflecting differences between assessment tools. The intervention also improved anxiety and insomnia symptoms, though it did not affect depression.
Metagenomic sequencing and metabolite profiling of fecal samples showed the intervention group to have significantly altered fecal metabolites, with the researchers identifying purine metabolism and butanoate metabolism as the most affected pathways. Butyric acid abundance was considerably higher, which the authors said may have contributed to stress relief by enhancing serotonin (5-HT) production.
The intervention was also found to boost beneficial bacteria like Lacticaseibacillus and reduce potentially harmful bacteria like Shigella and E. Coli.
However, no significant changes in inflammatory markers IL-1β and TNF-α were observed, which the researchers suggest could be perhaps due to the short intervention period.
The study concluded that although K56 showed promise for stress relief in this population, limitations include a geographically restricted sample and lack of strict dietary controls.
It noted that “to comprehensively elucidate its therapeutic efficacy and underlying mechanisms, future investigations should encompass large-scale, long-term randomized controlled trials.”
Journal: Frontiers in Nutrition. Source: Volume 12 - 2025. doi: 10.3389/fnut.2025.1544713. “Effects of Lacticaseibacillus paracasei K56 on perceived stress among pregraduate students: a double-blind, randomized, placebo-controlled trial”. Authors: Guan, Y. et al.