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It is difficult to overstate the importance and complexity of the gut microbiome. It does so much more than just impact the gastrointestinal system and intestine. Humans live in symbiosis with hundreds (and possibly thousands) of species of bacteria (1). Additionally, archaea, fungi, viruses, and protozoa are also present in our gut. In fact, only about 10% of the cells within our bodies are “ours” and contain human DNA. The remaining 90% of cells we carry with us are microbial. The exact makeup of the gut microbiome varies greatly from individual to individual and is influenced by variables that include diet, exercise, medication use, sleep, stress, hormonal changes, aging, and disease. Associations have been found between the composition of the microbiome and obesity, diabetes, hypertension, heart disease, autoimmune disorders, allergies, mood disorders, and more.
The gut bacteria participate in the digestion, absorption, and metabolism of proteins and carbohydrates and in the breakdown of endogenous intestinal mucus. They also synthesize vitamin K2 and various B group vitamins, and they influence the development of gut-associated lymphoid tissues and the development of cells of the immune system (2) and serve to limit the colonization of pathogenic bacteria. The majority of these bacteria are anaerobic. Common genera of this microbiota include Escherichia, Bifidobacterium, Lactobacillus, and Enterococcus.
A recent study examined the connection between the gut microbiome and COVID-19. Investigators found that patients hospitalized for COVID-19 had an increase in certain bacterial species and a decrease in others when compared to a control group, even after antibiotic use was accounted for (19). They found a negative correlation between disease severity and concentrations of Faecalibacterium prausnitzii and Eubacterium rectale. Patients were monitored for 30 days post-recovery, and the observed changes persisted. They postulated that these changes may contribute to the persistence of symptoms and multi-system inflammation that is sometimes seen with patients who have recovered from COVID-19.
In recent years, many studies have examined associations between the gut microbiome and obesity. When germ-free mice are colonized with gut bacteria from obese ones, they gain weight; but when they are colonized with gut bacteria from lean ones, they do not gain weight (3). They also gain weight when they are colonized with bacteria from severely overweight humans. In a discordant twin study, colonization from obese twins caused them to gain weight while colonization from their lean siblings did not (4). Some believe the ratio of Bacteroidetes bacteria to Firmicutes bacteria may play a significant role as well. One study found that as severely overweight individuals lose weight, the concentration of Bacteroidetes bacteria increases (5). Furthermore, genetically obese mice contain a higher proportion of Firmicutes bacteria than thin ones consuming the same diet, and thin mice contain more Bacteroidetes bacteria than overweight ones consuming the same diet (6). When investigators employed machine learning to study this topic, they concluded that the association between the Bacteroidetes / Firmicutes ratio and obesity is relatively weak and that existing studies lack significant sample sizes (7). The science is far from settled.
Studies have also investigated the link between the gut microbiome and diabetes. Some speculate that in individuals who are genetically susceptible to type 1 diabetes, it is ultimately a shift in the gut microbiome that triggers the onset (8). The gut microbiome of children with type 1 diabetes has been found to be less diverse than that of children without the disease (9). A recent review of 42 studies that examined the gut microbiome and type 2 diabetes found Bifidobacterium bacteria, Bacteroides bacteria, Faecalibacterium bacteria, Akkermansia bacteria, and Roseburia bacteria to be negatively associated with type 2 diabetes; and Ruminococcus bacteria, Fusobacterium bacteria, and Blautia bacteria to be positively associated (10). Other work has shown that when individuals with metabolic syndrome were given fecal transplants from healthy donors, insulin resistance improved (11).
The ratio of Bacteroidetes to Firmicutes bacteria in the microbiome has also been implicated in hypertension. Consuming milk fermented with Lactobacilli bacteria can lower blood pressure in some cases, and Lactobacilli produce peptides that can inhibit ACE1 (12). The same bacterial species found within the atherosclerotic lesions of individuals with cardiovascular disease are found in their gut (13). Additionally, Akkermansia muciniphila bacteria may have a cardioprotective effect. Investigators observed that when mice were fed a Western diet, they experienced a decrease in Akkermansia muciniphila and an increase in atherosclerotic lesions. When these same mice were recolonized with Akkermansia muciniphila, a reversal in atherosclerotic lesions was observed (14).
Components of the gut microbiome may be involved in eliciting or quelling immune responses that lead to the development of autoimmune disorders and allergies. Antibodies directed against a yeast species, Saccharomyces cerevisiae, have been found in patients with rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and Crohn’s Disease (15). Individuals with these conditions show an increase in the numbers of certain bacterial species and a decrease in other species – as do individuals with multiple sclerosis, Sjögren’s syndrome, and celiac disease. The ratio of Clostridium difficile bacteria to Bifidobacterium bacteria in infants has been associated with food and aero-allergies, and high levels of fecal Escherichia coli bacteria in infants are associated with IgE-mediated eczema (16).
The central nervous system and enteric nervous system (together known as the gut-brain axis) are both influenced by the gut microbiome. Bacteria in the gut can directly secrete neurotransmitters, including serotonin, dopamine, norepinephrine, GABA, and histamine. This is especially interesting since there are a lot of receptors for these neurotransmitters throughout the gastrointestinal system and intestine. Several studies have shown that patients with bipolar and major depressive disorder have an increase in Actinobacteria bacteria and Enterobacteriaceae bacteria, and a decrease in Faecalibacterium (17). Mice treated with Lactobacillus rhamnosus bacteria have reduced anxiety/depression-like behavior and altered expression of GABA receptors (18). Differences in microbiome composition have also been noted in patients with schizophrenia, Parkinson’s disease, and an autism spectrum disorder.
Fecal microbiota transplantation (FMT) is currently being used as a treatment for Clostridium difficile colitis. In fact, FMT is more effective than vancomycin in treating recurrent Clostridium difficile colitis. Most commonly, FMT is performed via colonoscopy. Nasoduodenal tubes, nasogastric tubes, and enemas can also be used. FMT made headlines in 2019 when a transplant recipient died, and several others became seriously ill, after becoming colonized with multi-drug resistant Escherichia coli bacteria. This led the FDA to recommend new safety measures for FMTs, including screening donors for risk factors associated with carrying multi-drug-resistant organisms and testing all donor stools for such organisms.
In many regards, studying the microbiome and gut bacteria within often leads to more questions than answers. When a change in bacterial levels is observed in a disease state, it is sometimes difficult to know whether that change contributed to the disease state or merely resulted from it. Anyone who seeks to convince you that they know the perfect solution to optimizing gut health is misleading you. While a host of food products and health supplements are touted to enhance the gut microbiome, in most cases the details of this “enhancement” are not defined. As additional studies are conducted, we will gain a better understanding of this vast topic and will likely see an increase in the utilization of fecal transplants in treating various diseases. After all, the healthy human microbiome is a critical part of staying healthy.
GIDEON is one of the most well-known and comprehensive global databases for infectious diseases. Data is refreshed daily, and the GIDEON API allows medical professionals and researchers access to a continuous stream of data. Whether your research involves quantifying data, learning about specific microbes, or testing out differential diagnosis tools– GIDEON has you covered with a program that has met standards for accessibility excellence.
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