Abstract
Background/Objectives: Menopause-related issues—such as mood disturbance, hot flashes, and sleep disturbance—are thought to be influenced not only by hormonal changes but also by everyday stress and gut barrier-related host responses. Heat-killed Lactiplantibacillus plantarum L-137 (HK L-137) has shown immunomodulatory and gut barrier-related effects, but clinical evidence for its effects in menopausal women is limited. We investigated whether HK L-137 intake affects menopause-related outcomes and gut barrier-related biomarkers in women reporting daily stress. Methods: We conducted a 12-week randomized, double-blind, placebo-controlled, parallel-group trial in healthy Japanese women aged 45–69 years who self-reported daily stress (UMIN000055687). Participants were randomly assigned to receive one tablet containing 10 mg HK L-137 or placebo daily. Mood state, menopausal symptoms, and sleep quality—as menopause-related outcomes—and gut barrier-related biomarkers were assessed at baseline and week 12. Results: A total of 121 participants were included, and 119 completed the study. No significant between-group differences were observed in the questionnaire scores of mood state, menopausal symptoms, or sleep quality. Changes in serum soluble CD14 (sCD14) and lactate dehydrogenase (LDH) differed significantly between groups, favoring the HK L-137 group (p = 0.020 and p = 0.010, respectively). In the prespecified subgroup with higher baseline levels of negative mood, HK L-137 significantly improved hot flashes item and sleep maintenance score, and was associated with favorable changes in sCD14, LDH, and body mass index versus placebo. No intervention-related safety concerns were identified. Conclusions: HK L-137 favorably affected sCD14 and LDH in the overall analysis and improved selected menopause-related outcomes in women with higher baseline levels of negative mood. These findings suggest a possible role of gut barrier-related host responses associated with microbial translocation.