General Precision Point Diagnostics January 26, 2024

We’ve written many times over the years about the gut-brain connection and how the microbiome specifically influences not only the physical health of the gut but also the physical health of the brain. Inflammation in the gut can be triggered by food allergies, a lack of fiber in the diet, and courses of antibiotics among other things. Each of these things can cause a leaky gut- a loosening of the tight cellular junctions in the intestinal wall- that can permit inflammatory markers to spread in the bloodstream, causing inflammation elsewhere in the body. In addition to this mechanism for bodywide inflammation, the gut communicates directly with the brain through the vagus nerve. Inflammation in the gut, and even changes in the composition of the microbiome, can trigger or suppress specific chemicals in the brain. Some of these reactions in the brain can decrease dopamine, serotonin, or other modulators of mood and energy and create states of depression, boredom, anxiety, lassitude, or other mental states and conditions. The opposite is true as well- a balanced, healthy microbiome- with the right mix of good bacteria, can result in healthy and happy mental states. It’s important to realize that your microbiome is almost a separate (group) entity that evolved symbiotically with us. A healthy microbiome means a healthy, happy brain, because evolutionarily if the microbiome was in distress it would signal the brain to have the body withdraw from the crowd, recover, and reset- something that’s not always possible in the modern world.

There have been many animal studies that have demonstrated these connections, and some human studies that examined specific mechanisms, including those that demonstrated the communication means of the microbiome to the brain via the vagus nerve. There have also been studies that specifically linked depression to the microbiome in animals- for example, a study with rats that seeded their gut with bacteria from the gut of humans who had been diagnosed with major depression (Kelly, et al, 2016). The rats so seeded showed signs of depression by losing interest in pleasurable activities and showing altered levels of tryptophans (a compound associated with depression). The study concluded that “We demonstrate that depression is associated with decreased gut microbiota richness and diversity.” and that “the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.”. Although an animal study, it was still a pretty convincing bit of science and fit with many other studies that had outlined how the gut biota communicates with and affects the brain.

Now a new study, published in December 2022 in the journal Nature Communications, focuses on human subjects and the specific bacterial populations in the microbiomes of people diagnosed with depression. The study is noteworthy not only for attempting to nail down specific populations of gut bacteria and how they relate to depression but also for how large the study is. The authors, (Radjabzadeh, et al, 2022, linked above), utilized the Rotterdam Study- a large-scale analysis over the course of decades that attempted to take a comprehensive snapshot of the health of a large representative population of that city numbering in the thousands. Part of that study collected both questionnaires on depression and fecal samples from more than 1,000 individuals. The study added to this data by further collecting the same set of data from a second equally sized group of Dutch people and integrated and compared the data. The study authors noted how difficult it is to find a pathology for depression, how impactful that condition is, and therefore how urgent it is to find some sort of link that might offer a biochemical point of intervention. The study identified 13 gut bacteria that were known to be associated with the symptoms of depression and also were known to be involved in the synthesis of key neurotransmitters associated with mood regulation and depression (GABA, glutamate, butyrate, and serotonin). Not only does that make the selected bacteria relevant to depression, but also a demonstration of the gut-brain connection directly. The conclusions of the study were: 

“In this large study of 2593 individuals profiled for depressive symptoms and fecal microbiome, we identified 12 genera and 1 microbial family associated with depressive symptoms. These include genera Sellimonas, Eggerthella, Ruminococcaceae (UCG002, UCG003, UCG005), Lachnoclostridium, Hungatella, Coprococcus, LachnospiraceaeUCG001, Ruminococcusgauvreauiigroup, Eubacterium ventriosum, Subdoligranulum and family Ruminococcaceae. Sellimonas, Eggerthella, Lachnoclostridium, and Hungatella were more abundant in individuals with higher depressive symptoms. All other taxa were depleted in depression. Alpha diversity was significantly associated with depressive symptoms in both discovery and replication cohorts.” 

This is a great start in demonstrating a correlation between specific gut bacteria that are implicated in depression, including showing depletion and addition. Specifically, “Eggerthella has been consistently found to be increased in depression and anxiety cases in 8 studies25,26,28, which is in line with the findings of our study. MR analysis suggests a causal link between MDD and Eggerthella, which requires further investigation.” This is interesting because at least one Eggerthella (Eggerthella lenta) has been found to be associated with worsening colitis and was present with diet- particularly one low in Arginine (Alexander, et al, 2020– not yet peer-reviewed). Arginine is found in protein-rich foods and whole grains. Omega-3 fatty acid depletion is associated with Subdoligranulum, and since omega-3 depletion has also been linked with depression, that could suggest a mechanism for that as well. “Our study suggests that the gut microbiome composition may play a key role in depression.” is also a key takeaway from this study. While the authors go into detail about how each of these bacteria may specifically contribute to or be implicated in depression, the larger question is what to do about it. How can this knowledge be utilized for the common person?

One obvious starting point is to have a patient suffering from depression take a comprehensive stool test to assess the composition of microbes in that patient’s microbiome and then craft a gut treatment from there. Physical support for the gut might really move the needle psychologically for some patients.

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