You are What You Eat; The Influence of the Intestinal Microbiome on Behavior

Ishaan Gollamudi
5 min readJan 28, 2020

The importance of the stomach cannot be overstated, yet there is still so much more to the intricacies of the gut that have not been explored to their full capacity, only the mildest blemishes upon their surface. The best example of this is the intestinal microbiome: your gut bacteria, and the complex ways they influence nearly all bodily functions.

This article will focus on the gut-brain axis specifically, and how the enteric nervous system and central nervous system (ENS and CNS respectively) rely upon the intestinal microbiome to maintain homeostasis.

The primary functions of gut bacteria are to modulate gut motility and secretions, maintain normal mucosal immune function and epithelial barrier integrity, as well as monitor nutrient absorption. The ENS, of which this microbiome is a critical component, communicates with the CNS via neural, neuro-endocrinal and immune pathways, providing a veritable stream of information, including information on bacterial metabolites from the luminal epithelial chemosensors. However, information isn’t the only thing being transferred via these pathways, neurochemicals are transmitted too, providing some of the clearest evidence of inter-kingdom signaling and thus a common ancestor ever seen. The gut was often called the second brain for the sheer interconnectedness of the ENS with all parts of the body, but now we can understand just how accurate that label was, especially when you consider that, as an example, gut bacteria synthesize 95% of the body’s supply of serotonin.

Gut bacteria seem to influence the regulation of stress, depression, anxiety and cognition, with bacteria-free mice displaying deficits in non-spatial and working memory tasks, with definite increases in the stress hormones corticosterone and adrenocorticotropic hormone, as well as brain-derived neurotrophic factor, which in involved with neuronal growth and survival, possibly as a method of compensation for the lack of such a vital component of the gut-brain axis. Studies have shown that germ-free mice show greater exploration when placed in unfamiliar open-field boxes, suggesting lower levels of vigilance/caution. There is also the decreased expression of NMDA subunit 2A and serotonin receptors in the amygdala and hippocampus.

Citrobacter rodentium infections notably increased anxiety levels in mice, as well as c-FOS levels in the vagus nerve. Campylobacter jejuni had a similar effect. However, ingestion of Lactobacillus rhamnosus seemed to decreases stress-induced anxiety and depression-like behavior in mice, whilst also reversing the transcription of mRNA expression of GABAA and GABAB receptors in the hippocampus, hypothalamus, pre-frontal cortex and amygdala regions. But the most definitive proof of the integral role of bacteria in the gut-brain axis was Toxoplasma gondii, which has been well known to change the behaviour of mice so drastically that they lose all fear of naturally predatory animals, such as cats. It also removes the human fear of danger almost completely, when introduced into a human intestinal microbiome. In some cases, patients have been known to walk directly into oncoming traffic, although evidence of behavioral changes is still tentative, hindered further by the fact that up to half of the human population may be infected with T. gondii, but do not display symptoms.

The intestinal microbiome influences the human body to the extent that an individual’s sleep appears to owe some part of its architecture to neurochemicals produced by their microbiome. Bacteria, bacterial peptides to be specific, induce T-cells and intestinal macrophages to produce interleukin-1beta and tumor necrosis factor alpha (IL_1b and TNFa respectively). Bacterial cell wall components: lipopolysaccharides, induce synthesis of IL-18, which, along with IL-1b and TNFa, induce non-REM sleep (nREM). Cortisol inhibits this immune cell synthesis of cytokines, hence why stressed individuals, especially the perpetually stressed individuals of the modern world, are sleeping for far shorter times than would be ideal: 40% of Americans for around 6.8 hours per night. These cytokines do rise and fall in circadian rhythm, as an aside, peaking at midnight, but declining in the morning as cortisol levels rise. Moving to something more serious, schizophrenic patients express increased levels of gut bacteria translocation, perceived to be a responsible to inflammation, and the presence of marker CD14 tripled the risk of schizophrenia, being associated with C-reactive protein, which in turn is known to stimulate monocyte activation. This appears to suggest that some, as yet unknown, bacterial-synthesized compounds may be stimulating monocyte activation.

Luckily, science has been able to pinpoint which genuses produce which neurochemicals, Lactobacillus species producing acetylcholine and gamma-amino butyrate (GABA), Bifidobacterium species producing GABA; Escherichia producing norepinephrine, serotonin and dopamine, Streptococcus and Enterococcus produce serotonin, and Bacillus species produce norepinephrine and dopamine, potentially opening up pathways to treat mental illnesses without anti-depressants, painkillers and all the controversy around not only the medicines themselves, but those who manufacture it. I, myself, having seen their addictive and often fatal nature at close hand, one readily thinks of the deaths of Juice WRLD, Lil Peep, Prince, Michael Jackson, Heath Ledger, Whitney Houston and the near death experience of Eminem, to name but a few, would prefer to avoid such medication for anything, noting especially how it has proliferated the average household as a treatment for something as mild as a headache.

Although the recent rise in mental health awareness has increased the rate of diagnosis of disorders, although that has its own problems, it has generally been widely accepted that each future generation, most especially Generation Z, has become increasingly depressed and/or anxiety-ridden. Though there is a whole host of factors that could be influencing this meteoric rise, there may be one that has been overlooked the whole time: diet. The Western Diet of high saturated fat and sugar content has dominated the globe, playing a large part in the obesity epidemic. But one thing that has been repeatedly brought up and just as rapidly buried is the importance of fibre, elusive in today’s world of prepackaged food. The average adult eats 15 grams a day, a far cry from the 25 grams women require and the 38 grams men require on a daily basis. This fibre, broken down by these bacteria, is one of the most essential components to the human diet, and was readily available until processed, and to that extent extremely over-processed, food permeated the market.

Perhaps the secret to being happy and healthy isn’t some sort of obscure concept practiced by an obscure congregation of monks who live in such seclusion that it begs the question of how they found it in the first place. Perhaps the secret lies in the choice one makes every morning, to reach for the fruit basket and yogurt container, or the brightly emblazoned cereal box.

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