Abstract & Commentary
Beneficial Brain Bacteria: Fermented Milk and Your Noggin'
By David Kiefer, MD, Editor
Synopsis:In healthy women, the group receiving a fermented and probiotic-supplemented milk beverage showed baseline resting brain network changes and decreased responses to negative imagery.
Source: Tillisch K, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 2013;144:1394-1401.
There is some animal research showing a connection between the contents of the intestinal microbiota and neurological activity (including pain) and behavior, although there are limited human data exploring these relationships, an aim of this research study. In this 4-week trial, healthy women were randomized to one of three groups: 1) twice daily fermented milk product supplemented with probiotics (n = 12), 2) twice daily non-fermented milk product (n = 11), or 3) no intervention (n = 13).
The study participants were aged 18-55 years and were recruited from the community by an advertisement. Women were excluded if Bifidobacterium lactis was found in a pre-examination of their stool (representing possible effects of a non-allowed probiotic ingestion), if they had taken antibiotics or probiotics in the month before the study, or if their compliance with the study protocol was less than 75% of the doses provided.
The researchers described, in depth, the bacteria present in the fermented milk product, providing information that probably indicates the level of detail future clinical discussion on this topic will contain (see Table). The doses of the three probiotic species are also listed in the Table. The control milk product contained the same amount of lactose as the intervention milk product, but without the probiotic strains. Approximately one-half cup (125 g) of each of these milk products was given to study participants twice daily.
Table:Probiotic Strains Present in the Fermented Milk Product
Study participants had their stool analyzed for bacterial content before and after the intervention. In addition, functional magnetic resonance imaging (fMRI) was taken of each study participant as they were presented with either emotional faces attention tasks using negative affect (fear and anger) or control tasks with geometric forms. Comparisons were made between different brain regions and their respective activities. In addition, an estimate of resting brain activity was made using a complicated series of computer calculations from the MRI images (" resting scan correlation maps were calculated in Statistical Parametric Mapping using the peak voxel from 3 clusters of interest in the Partial Least Squares Analysis as seeds.") The original article describes this complex process in more detail should readers be interested.
There were some dropouts in this study, including two people who took antibiotics, six with B. lactis positive stool at baseline or in the control groups, and one in the probiotic milk group who did not have B. lactis in ther stool and was presumed non-compliant. Of the subjects analyzed, the researchers found that study participants ingesting the probiotic milk product had a lessened response to emotional tasks in areas of the brain containing affective, viscerosensory, and somatosensory cortices when compared to the control tasks (P = 0.004). A series of fMRI brain images accompanied this paper, demonstrating these changes graphically. In addition, the treatment group showed changes in intrinsic activity of the resting brain, more specifically in midbrain connectivity, which the authors postulate could explain the observed decreased responses to the emotional tasks in the probiotic milk product group. The authors make an analogy between the resting brain state and a template, in that the brain can respond quickly to the environment from the baseline template that has been created.
Interestingly, the researchers failed to find differences between groups in microbiota content of the stool after the intervention period.
The implications of these results, if replicated and expanded to other demographics, could be far-reaching. Imagine a day when we treat pain or mental health conditions with fermented foods or probiotics as adjuvant therapies to allopathic approaches, or maybe even the first-line treatments themselves. The researchers here extend animal trials to the human realm, finding what the authors claim are "widespread" changes in how the brain responds to a negative context. A fermented milk product seems to change brain activity; "Got Milk?" advertisers are going to have a field day with this.
There are mechanisms that could explain these findings, including numerous animal research references offered in the article for changes in afferent vagal signaling or systemic amino acid and polysaccharide metabolism from probiotic supplementation. As this experiment was not designed to specifically test the mechanisms of action, the authors hedge their bets by offering several competing hypotheses and metabolic pathways by which gut flora could account for the changes seen. For example, the authors allude to "monoaminergic modulation of multiple brain areas," mediated by the vagus nerve, referencing studies that show a vagal effect on the nucleus tractus solitarius, a key connector to many other areas of the brain. They also hypothesize that some cerebral effects from probiotics may occur from systemic metabolic changes.
It is a methodological flaw that the dropouts were not included in the statistical analyses as intention-to-treat. Furthermore, no discussion was offered to explain the lack of stool colonization changes in the fermented milk product group as compared to the other group. If the probiotic supplementation were successful in delivering live bacteria to the colon to the point where it was causing the posited metabolic and vagus-mediated shifts in brain activity, some change in stool microbiota should be seen. It definitely leads to confusion as far as the mechanisms behind the results. On that note, a control population is useful for some of the statistical analyses, but doesn't control for a placebo effect, which could be at play here.
My prediction is that the floodgates have opened on this intriguing topic: the whole body effects of the gut microflora. Perhaps this study wasn't perfectly designed or executed, but there is a growing body of evidence in animal and human research for probiotic effects on many organs, even the brain. Future research will surely help us understand this better. It seems early to offer a definitive clinical guideline from this study as there are too many details needing corroboration. That said, provided safety can be assured (and most probiotic supplementation studies demonstrate a good safety profile), we should now start to wonder about the probiotic dose and species necessary for tangible brain effects, and encourage our research colleagues to explore this.