Microbiota present in the gastrointestinal tract influence brain functions through various mechanisms. Dysbiosis, caused by multiple factors including different pharmaceutical drugs and aging, is associated with health disorders involving the brain such as anxiety, mild to moderate depression, chronic pain, Parkinson’s disease, cognitive decline and Alzheimer’s disease. Therapies used to treat dysbiosis such as dietary therapy, probiotics, prebiotics, and oral or fecal bacteriotherapy alleviate signs and symptoms of disease. Using probiotics to treat an altered gut-brain axis is supported in various animal models as well as a few clinical trials. Additional robust clinical trials demonstrating the efficacy of probiotics in treating mental health disorders are needed, particularly in elderly populations.
In this randomized, double-blind, placebo-controlled, multicenter clinical trial, healthy community-dwelling older adults (>65 years of age) (n=63) consumed either placeboi or probioticsii containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. Blood and stool samples were collected, and a compliance check was performed, at the onset of the study and then at monthly intervals. Self-reports of intestinal health, including any changes in bowel habits, as well as anthropomorphic measurements, such as height, weight, and body mass index, also were collected at each visit.
Blood samples were tested for the presence of brain-derived neurotrophic factor (BDNF) using enzyme-linked immunosorbent assay (ELIZA). Stool samples were analyzed for changes in numbers and types of bacteria using 16sRNA technology and bioinformatics. Neuropsychological tests to assess brain function, namely Consortium to Establish a Registry for Alzheimer’s disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule were conducted at the onset of the study as well as week 4 and week 12.
Compared to placebo, probiotics significantly increased serum levels of BDNF, reduced numbers of inflammation-causing bacteria and significantly improved mental flexibility and stress scores. Probiotics also significantly improved scores in frequency of gas passage and abdominal distension; although, no other improvements in bowel habits reached clinical significance compared to placebo. No clinically relevant adverse events were reported during the study. The authors concluded that probiotics caused positive changes in gut microbiota, promoted mental flexibility and alleviated stress in healthy older adults.
The strengths of this study include: 1) rigorous inclusion and exclusion criteria, 2) relatively frequent visits by participants to take blood and stool samples and monitor adherence, 3) measuring BDNF; a pivotal link in the brain-gut axis and a well-known biomarker for brain function including learning, memory function and stress, 4) using multiple validated questionnaires to assess brain function, and 5) using older adults that lived in the community rather than in an institution. No restrictions were placed on the participants diet or health-related activities and therefore, finding significant positive results, regardless of the many potential confounders of independent living, strengthens the treatment effect delivered by probiotics. Moreover, using community-dwelling adults is more applicable as generalized health strategy to a larger population group of elderly individuals.
The potential weaknesses of this study are: 1) the use of questionnaires which rely on personal recall and therefore, include bias, 2) measuring only serum BDNF; including other blood biomarkers may have provided further insight into possible modes of action, 3) the use of stool samples and 16sRNA technology to determine changes in microbiota; current scientific evidence suggests there is limited correlation between bacteria detected in stool and microbial changes in the intestine, and 4) the use of soybean oil in the probiotic as well as placebo. Soybean oil is not inert and will influence the activity and growth of both probiotic and gut bacteria.
This study is one of an increasing number of studies indicating that supplementation with specific strains of probiotics positively influences brain functions through a brain-gut axis. The evidence from this well-designed clinical trial supports using probiotics to restore and/or maintain cognitive function and mental health, especially in older adults.
Kim CS, Cha L, Sim M, Jung S, Chun WY, Baik HW, Shin DM. Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. J Gerontol A Biol Sci Med Sci. 2021 Jan 1;76(1):32-40
i Placebo contained 500 mg capsule of soybean oil
ii Probiotic was consumed as 2 capsules containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI in soybean oil after the morning and evening meal to a total of 1X109 cfu/day