“Laughter is brightest in the place where the food is.”
– Irish Proverb
Or to phrase it more simply:
“Good food, good mood.”
But is it really just about the food, or is there a deeper connection? Is there something that dwells deep inside all of us that responds to the food we eat with a primal joy? And if so, does the converse hold, that is, do poor food choices lead to sadness and more serious and lengthy conditions like depression?
Recent research suggests the answer is, “Yes,” and our individual gut microbiome maybe that central connection.
Clinical depression is characterized by persistent negative mood, diminished interest, cognitive impairment, and sleep disturbances. According to data from the World Health Organization (WHO) in 2021, the number of people suffering from depression exceeded 280 million worldwide. Even more worrisome is its increasing prevalence amongst younger generations, with current estimates placing it at about 15% among adolescents. Depression affects outcomes in those with chronic diseases and delivers a negative economic impact through impairing occupational factors. It also carries a negative social impact, as well. Depression is currently the second leading cause of years lived with disability (YLD) worldwide.
Pharmacotherapy and psychotherapy are the current dominant treatment modalities. However, pharmacological treatments can induce untoward and adverse effects, while psychotherapies typically require substantial time and resource investments. As noted in past columns here, there is increasing data regarding the role of gut microbiome in modulating emotional and behavioral responses. Accumulating evidence supports the involvement of the microbiome-gut-brain (MGB-Axis) as a critical player in the cause of depressive symptoms.
A common finding across various studies is that the gut microbiome is altered in those with depression compared to healthy controls. The gut microbiome shifts towards a of pro-inflammatory composition with noticeable reductions in anti-inflammatory microbiota populations. But is more than just the presence of certain bacterial characters that impacts our mental health, gut microbiota influence emotional and behavioral states through bioactive metabolites, including short-chain fatty acids (SCFAs), neurotransmitter-related molecules, and trimethylamine N-oxide (TMAO). These microbial-derived metabolites are a massive part of the ongoing bidirectional communication between our gut and our brain.
This week’s Study Spotlight focuses on a recent meta-analysis that looked at treatment modalities aimed at correcting the microbiome pathologies, specifically using fecal microbiota transfer, or FMT.
- In this meta-analysis 12 trials consisting of 681 participants was analyzed.
- FMT statistically significantly reduced depressive symptoms.
- Both oral capsule and direct gastrointestinal administration (endoscopic or enema routes) were effective, with greater effects seen in direct gastrointestinal delivery.
- Improvements were most notable in the short- to mid-term; effects diminished by 6 months.
- Subgroup analysis showed more potent effects in patients with irritable bowel syndrome (IBS) than in those with neurological/psychiatric-related conditions.
The Caveat:
Disorders of gut-brain interaction (DGBIs), particularly irritable bowel syndrome (IBS), are characterized by chronic gastrointestinal symptoms such as pain, motility disturbances, dysbiosis, and immune activation in the absence of structural abnormalities. IBS exhibits one of the highest rates of psychiatric comorbidity among gastrointestinal disorders. This study suggests that targeting gut microbiota represents a promising therapeutic strategy for depression, with potential mechanisms including modulation of inflammatory pathways, microbial metabolite production, and gut-brain signaling.
Although the earliest documented use of FMT can be traced back to 4th century China when the physician Ge Hong described giving a “yellow-soup” fecal slurry to treat severe diarrhea and food poisoning, it was not used in Western modern medicine until 1958, where it was used to treat patients with severe pseudomembranous colitis. Fecal microbiome transplantation (FMT) restores gut microbial homeostasis by transferring microbial communities from healthy donors into the recipient’s gastrointestinal tract. This treatment now also appears as a possible treatment for depressive symptoms.
This meta-analysis suggests that FMT may offer short- to mid-term improvements in depressive symptoms across various clinical populations, with a potentially greater benefit observed in patients with disorders of gut-brain interaction such as irritable bowel syndrome. Although not examined in the trial, a possible factor affecting the durability of results could be related to the recipients diet. Since diet is involved in the ultimate composition and character of the gut microbiota, reverting to a preintervention diet following FMT could be causal in reducing long-term efficacy by providing an environment conducive to a pre-intervention microbiome.
However, the certainty of this evidence is constrained by the need for high-quality, adequately powered randomized controlled trials employing standardized methodologies, consistent depression outcome measures, comprehensive microbiota analyses, and systematic reporting of confounding factors. In addition, future studies need to account for dietary input, regimens, and changes.
What this study does emphasize is that the bidirectional regulation of the gut-brain axis is critical. As the authors observed, “FMT can modulate the gut microbiome composition or function, reduce systemic inflammation, and promote neurotransmitter synthesis, thereby concurrently improving gastrointestinal dysfunction and mood symptoms. Moreover, individuals with IBS often exhibit compromised gut barrier function and dysbiosis. These pathological conditions can exacerbate depressive symptoms by activating vagal nerve pathways and immune-inflammatory responses). FMT’s targeted restoration of the gut microenvironment in such cases may lead to more pronounced benefits for this subgroup.”
The take-home message is the increasing importance of the MGB-Axis in mental illness and the role of our diet in both physical and mental well-being.
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