Within our bodies, trillions of cells originating from a single-celled zygote work in harmony to create and sustain us. However, residing in our guts is a vast and complex microbiome that, despite its integral role, remains largely unexplored. “The current estimate is that humans have 10 trillion human cells and about 100 trillion bacterial cells,” says Dr. Martin J. Blaser at the New York University School of Medicine. These microbes play an essential role in supporting healthy digestion, offering infection prevention, and even preserving reproductive health, as well as linking the gastrointestinal tract to the enteric nervous system. Scientifically, the 'gut-brain axis' refers to the bidirectional interaction between gut microbiota and the brain, mediated through neural, endocrine, immune, and humoral pathways. This interaction has been extensively demonstrated to influence brain activity.
The gut-brain axis involves complex communication between the central nervous system (CNS), the autonomic nervous system (ANS), the enteric nervous system (ENS), and the hypothalamic-pituitary-adrenal (HPA) axis. The ANS, including the sympathetic and parasympathetic systems, transmits signals between the gut and the brain. For example, in response to stress, pro-inflammatory cytokines like IL-1β can prompt the adrenal glands to release cortisol, a major stress hormone. Beyond neural pathways, the gut-brain axis also operates through the immune system, where gut microbiota plays a crucial role in regulating immune responses, such as cytokine production and T cell development. Key gut bacteria, including Helicobacter, Bacteroides, Clostridia, and segmented filamentous bacteria, help balance pro-inflammatory and anti-inflammatory signals. For instance, when the intestinal barrier is compromised, gut microbes can trigger immune cells to release pro-inflammatory cytokines like IL-1β, IL-6, and TNFα into the bloodstream, potentially leading to systemic inflammation.
"Humans are estimated to have 10 trillion human cells and about 100 trillion bacterial cells"
These interconnected systems—neural, immune, and endocrine—profoundly affect the brain and mental health. Research has shown that several neurological conditions, including Alzheimer's disease (AD), Parkinson's disease, anxiety, depression, and Autism Spectrum Disorder, are influenced by the so-called 'dysbiosis' of the gut microbiota.
One of the most well-documented examples of gut dysbiosis associated with a neurological condition is the overgrowth of Helicobacter pylori in the intestines of Parkinson's disease patients. H. pylori infection has been shown to reduce dopaminergic transmission in neurons located in the substantia nigra, a brain region critical for motor control. This reduction in dopamine transmission may correlate with the progressive motor dysfunction, gastrointestinal issues, and cognitive impairment seen in Parkinson's disease. Additionally, studies have found an increase in bacteria from the families Lactobacillaceae, Enterococcaceae, and Barnesiellaceae in Parkinson’s patients, which may further contribute to disease progression. Meanwhile, a decrease in Prevotellaceae has been linked to reduced production of the hormone ghrelin, which is essential for proper dopaminergic transmission.
Gut dysbiosis is also a significant factor in the context of AD. A study analysing stool samples from patients measured the abundance of six bacterial taxa, revealing an increase in pro-inflammatory species and a decrease in anti-inflammatory ones. This imbalance included a reduced population of Firmicutes and a potential increase in Bacteroidetes. While the amyloid hypothesis remains a central explanation for AD, there is limited information related to how gut dysbiosis and the tau hypothesis might also contribute to disease progression.
"Studies have found an increase in bacteria from the families Lactobacillaceae, Enterococcaceae, and Barnesiellaceae in Parkinson’s patients (...)"
Given the emerging links between gut dysbiosis and these neurological conditions, several treatments aimed at restoring a healthy microbiome are being explored. In Parkinson's disease, microbial replacement therapy, which includes the transfer of liquid fecal matter from a healthy donor (fecal microbiota transplantation), has shown promise. Additionally, probiotics containing strains of Lactobacillus and Bifidobacterium have been effective in alleviating some gastrointestinal symptoms in patients when administered over a period of 1-3 months.
Similarly, early studies in Alzheimer's patients have shown that treatments such as fecal microbiota transplantation and probiotics could be beneficial. Although these studies have been conducted on small groups, they offer promising results that warrant further investigation. Nonetheless, research into restoring gut microbiota is still in its infancy and demands more intensive study to gain conclusive results.
This article was written by Shriya Singh and edited by Julia Dabrowska, with graphics produced by Lilly Green. If you enjoyed this article, be the first to be notified about new posts by signing up to become a WiNUK member (top right of this page)! Interested in writing for WiNUK yourself? Contact us through the blog page and the editors will be in touch.
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