It is estimated that 100 trillion microorganisms representing more than 500 different species inhabit the normal, healthy gastrointestinal tract of a human.1 These microorganisms do not always exist in a symbiotic state, promoting optimal health and wellness. Sometimes they become imbalanced, due to a variety of causes, and gastrointestinal distress and other symptoms ensue. Scientists are learning about the the multitude of health benefits associated with consuming the right type and levels of microbes, known as probiotics, to equilibrate the gastrointestinal tract and promote optimal health. Research has suggested that probiotics improve digestive function, help with the side effects of antibiotic therapy, and enhance immune function. 2
In this review article (an article reviewing a larger number of previously published scientific articles), the authors reviewed both human and animal studies over the past 66 years.3 When evaluating the whole body of data regarding probiotics and central nervous system function, probiotics appear to have a positive effect on central nervous system function. Most of the studies used Bifidobacterium and Lactobacillus preparations, and most of them were effective in improving central nervous system functions. An intake of probiotics for 2 weeks in animals and 4 weeks in humans was sufficient to result in measurable effects.
The authors of this article reviewed both human and animal studies in articles published from 1950 to April 2016 that included the phrasing “probiotic or gut microbiota” and “behavioral or central nervous system”. After review of the related abstracts, the authors further evaluated those that involved an intervention with probiotics and that tested central nervous system function.
The outcomes of each study were described and a qualitative synthesis was created to determine which probiotic interventions at which specific dose and duration were most effective with regard to certain central nervous system functions. In total 38 studies were evaluated, with 13 involving only humans, 23 involving only animals, and 2 involving both human and animal research.
All of the animal studies conducted were on rodents (mice or rats). Of the 25 animal studies, 18 involved the evaluation of only a single strain of probiotics. Seven of the studies used Bifidobacterium, 11 used Lactobacillus, and one used Clostridium (one used both Bifidobacterium and Lactobacillus).
Twelve of the studies tested anxiety-like behavior in the animals. Multiple studies showed less anxious behavior in the rodents when treated with a single strain of probiotic, including Bifidobacterium longum (n=3), Lactobacillus helveticus (n=2), Lactobacillus plantarum (n=2), Bifidobacterium breve (n=1), Lactobacillus fermentum (n=1), and Lactobacillus rhamnosus (n=2, but only 1 showed reduced anxiety behaviors). Finally, two studies using a multi-strain therapeutic approach, ((L. rhamnosus and L. helveticus) and (B. Longum and L. Helveticus)) also found reduced anxious behavior in the rodents with treatment.
Nine animal studies focused on depression. B. longum, B, breve, L. rhamnosus, L. helveticus, and B. infantis were each used as a single therapy in separate studies with positive results. B. infantis was used in a second study that did not result show reduced depression-like behavior. Two studies evaluated L. plantarum, but the probiotic only had an effect in the mice that had an early-life stress of maternal separation. One study using combination therapy with B. longum and L. helveticus also showed positive effects associated with reduced depression-like behavior.
Eleven of the animal studies evaluated cognitive function, and they all showed the probiotics to be beneficial for memory performance. Spatial memory ability, the part of memory responsible for recording information about one’s environment and its spatial orientation, was improved by L. fermentum and Clostridium. When used singularly, B. Longum, B. breve, and L. helveticus were all effective on spatial and non-spatial memory. Combination therapy with L. rhamnosus and L. helveticus was effective in improving non-spatial memory, as was B. longum used in concert with L. helveticus. Also, combination therapy of Lactobacillus acidophilus, B. Lactis, and L. fermentum improved spatial memory, as did the combination treatment of L. plantarum and Lactobacillus curvatus.
Bifidobacterium fragilis improved behaviors related to autism spectrum disorder, including communicative behavior, anxiety-like behavior, and sensory gating. Social interaction behavior was not improved though.
Of the 15 studies that involved human subjects, 8 used a single strain probiotic (L. casei, L. casei. subsp. rhamnosus, L. casei. Shirota, L. plantarum, and B. infantis), with two of the probiotics containing milk. The other seven studies used multi-strain probiotic interventions. In the human studies, doses of the effective interventions ranged from 107 to 3.63 × 1010, and the duration of the treatments ranged from 20 days to 8 weeks. Doses around 109 (n=5 of 8) and 1010 (n=3 of 8) were used most often. Treatment durations were most commonly 4 (6/15) and 8 (4/15) weeks.
Fifteen studies tested healthy participants on anxiety, depression, distress levels, mood state and behavior problems. One study compared a probiotic capsule (Lactobacillus casei, L. acidophilus, L. rhamnosus, Lactobacillus bulgaricus, B. breve, B. longum, and Streptococcus thermophilus) and a probiotic yogurt ( B. lactis and L. acidophilus) with the combination of conventional yogurt and a placebo capsule. The results indicated the probiotic capsule and probiotic yogurt were more effective in alleviating distress, anxiety, and depression in petrochemical workers. Another study using multi-strain probiotics found improvement in a measure of depression. Two studies found probiotic formulations of B. longum and L. helveticus could improve anxiety and depression in all participants. A study of chronic fatigue patients that used L. Casei Shirota found decreased anxiety levels after treatment, and another study using the same probiotic strain (but containing milk) showed an improvement in mood in only the bottom 1/3 of the depressed distribution at baseline. However, studies in various populations, including patients with irritable bowel syndrome treated with L. casei singularly and L. paracasei with L. acidophilus in concert, schizophrenics treated with L. rhamnosus, rheumatoid arthritis patients treated with L. casei, smokers treated with L. casei, and children with ASD treated with L. plantarum, showed no significant effect on outcomes measured. A study using L. casei Shirota that looked at different memory and cognitive abilities found decreased memory abilities in all participants when compared to the placebo, and had no effect on verbal or eating-associated behavior.
There were two studies that found reduced cortisol levels in saliva and urine after probiotic interventions with L. casei Shirota and multi-strain L. helveticus + B. longum. The immune system could be improved by the probiotic L. casei. The human study that investigated metabolites of the tryptophan pathway did not find any significant change by probiotics. Many of the human studies looked at bowel function, and found reduced difficulties in bowel movement, irritable bowel syndrome severity, and symptoms in patients. Fecal microbiota was altered, with Lactobacillus was increased and Clostridium decreased by L. plantarum, and Bifidobacteria and Lactobacillus were increased by L. casei Shirota.
B. longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei were most effective in improving central nervous system function, memory abilities, anxiety, depression, mood, stress response. The researchers concluded that the results of this analysis will hopefully lead to further study on the potential effects of probiotics used singularly and in combination to improve various central nervous system functions, including memory.
- Harvard Medical School. Health benefits of taking probiotics. http://www.health.harvard.edu/vitamins-and-supplements/health-benefits-of-taking-probiotics. Accessed September 12, 206.
- California Dairy Research Foundation. USProbiotics Home. http://cdrf.org/home/checkoff-investments/usprobiotics/ Accessed September 12, 2016.
- Wang H, Lee IS, Braun C, Enck P. Effect of probiotics on central nervous system functions in animals and humans – a systematic review. Journal of Neurogastroenterology and Motility. 2016;Epub ahead of print.