Research show how probiotic strains modulate brain processing and connectivity
The interconnection between the gut microbiome and brain interactions for neurotransmitter expression, neurodevelopment, and behavior is a relatively new area of science. Rodent studies abound, which supports the basic level of knowledge that multi-strain probiotics can influence this connectivity, however human studies are limited. This study elevates the foundation of knowledge by lending greater understanding to whole-brain functionality and structural connectivity of the gut-brain axis.
This research points to the therapeutic potential of specific probiotic strains capable of modulating pain sensitivity, stress responsiveness, mood, anxiety and depressive symptoms in a beneficial manner.
The researchers investigated the influence of a 4-week multi-strain probiotic regimen on whole-brain functional connectivity in healthy volunteers. They hypothesized that ingestion of multi-strain probiotics would serve to manipulate the gut influence functional connectivity in the resting-state networks (RSNs) and mediates emotional and higher-order cognitive functions. As such, they suspected that the salience network, executive network and default mode network would play relevant roles.
Study Methods
The study included forty-five right-handed healthy participants (mean age (years) = 26.24, SD = 4.76; 23 female; age group 20–40 years). The study participants were divided equally into three groups:
- Probiotics (PRP) group (received probiotics),
- Placebo (PLP) group (received placebo),
- Control (CON) group (received nothing).
During this period, all participants were instructed to fill in a daily diary about their gastrointestinal symptoms and details of probiotic/placebo intake [time of intake, method of intake (with milk/water/juice)]. Further, participants were instructed to maintain their usual diet and lifestyle habits during the 4-week period with any deviation recorded for later assessment.
The probiotic formulation used for this study is available on the US market as OmniBiotic® Stress Release. The product (7.5 × 106 CFU/g) is composed of nine bacterial strains, namely Lactobacillus casei W56, Lactobacillus acidophilus W22, Lactobacillus paracasei W20, Bifidobacterium lactis W51, Lactobacillus salivarius W24, Lactococcus lactis W19, Bifidobacterium lactis W52, Lactobacillus plantarum W62 and Bifidobacterium bifidum W23.
To test these hypotheses, the researchers performed resting-state fMRI and diffusion MRI scanning at two time points: at baseline (time point 1) and after 4 weeks (time point 2).
Ten independent components (ICs) were identified as resting-state networks (RSNs) from group MELODIC output, including: salience network (SN), auditory network (AUN), default mode network (DMN), left fronto-parietal network (LFPN), right fronto-parietal network (RFPN), middle and superior frontal gyrus network (MFGN), task-positive network (TPN), visual network (VIN), left temporo-parietal–frontal network (LTPF) and cortico-cerebellar network (CCN)
Study Results on Probiotic Strains and Brain Processing
The probiotic group showed a significant increase in salience network activity (associated with increased attention, perception, cognition) and significant decrease in default mode network and MFGN activity (associated with reduced distraction and improved reasoning, decision-making, learning, and creativity). The researchers noted that evidence from the vast literature on resting-state fMRI studies shows that efficient behavior involves the coordinated activity of large-scale networks and interactions between the networks control and shape our behavior.
More specifically:
- The PRP group exhibited increased functional connectivity (FC).
- Significant changes in FC were observed in PRP group as compared to PLP and CON groups, within the SN, DMN, VIN and MFGN resting-state networks.
- No corresponding structural differences were observed between the three groups.
- A significantly decreased FC was observed in the DMN in PRP group as compared to PLP group in frontal pole, superior frontal gyrus (SFG) and paracingulate gyrus.
- Decreased FC in the MFGN in the PRP group as compared to the CON group was also observed.
Previous research shows that the salience network plays an important role in mediating the function of other networks, particularly when a rapid change in behavior is required. “The SN dynamically controls functional connectivity the changes between the DMN, which is related to self-referential cognition, and the central executive network (CEN), which is related to external-oriented tasks,” the researchers write.
The cingulate cortex is a key structure of SN and together with the insula, plays an important role in initiating network switching between the DMN and attentional networks.
- FC changes in this region reflect the influence of probiotic administration on modulating behavior and a shift towards efficient attention control in the control group.
- FC changes in cingulate cortex were also reflected as changes in BOLD response emotional decision-making in a task-based fMRI study.
The study also showed coupled deactivation of DMN brain regions, which further reflects a shift towards efficient behavioral performance in PRP group. Studies show that a failure to deactivate the DMN is associated with attentional deficits. Another significant observation was a change in MFGN functional connectivity, which plays a key role in spatial attention, orientation, decision-making and cognitive control.
What are the Mechanisms and Clinical Applications?
There are several plausible molecular mechanisms that may explain the probiotic influence on behavior, including:
- The bidirectional gut-brain vagal connections signals mood modulating molecules, including serotonin precursors and GABA.
- Short chain fatty acid production serves to strengthen epithelian barrier function and integrity.
- Probiotic byproducts, such as chemicals, cytokines, hormones help regulate inflammatory response.
The scientists say that irrespective of the pathways, the results support the notion that communication between gut microbiota and brain is a dynamic process. It can be modulated by a targeted intervention, which leads to changes in behavior and brain function.
“Although the efficacy of probiotics in the treatment of gastrointestinal diseases is well documented, preclinical studies have shown that probiotic intervention has the potential to modulate pain sensitivity, stress responsiveness, mood, anxiety and depressive symptoms in a beneficial manner,” they write.
The Omni-Biotic scientific team wrote this response to the study: “Our dedication to developing deeply characterized, clinically relevant, and indication targeted probiotics has long been rewarded through inspirational stories and individual outcomes. But it is independent, controlled trials that truly elucidate a quantitative value. This study clearly demonstrates the influence of the Omni-Biotic Stress Release formulation to strengthen cognitive function and efficient decision making as measured by salience network activity, while reducing inattention and rumination as measured by default network activity. Taken together and in combination with the totality of the reported findings, we agree with the investigators that this work supports the role of targeted probiotics in the effective management of stress and mood disorders.”
Conclusion/ “The results of the current study are relevant in guiding future clinical studies to address the question whether probiotic intervention might be of use as an alternative or adjunct strategy to treat depression and mood disorders. Neuroimaging techniques, specifically MRI, stand out as potential candidates for studying the effects of probiotic intervention in humans non-invasively using multi-modalities, ranging from functional MRI, magnetic resonance spectroscopy to diffusion tensor imaging.”
