Disruptions

Any unbalance, also called dysbiosis, in the microbiome is associated with the onset and progression of a range of chronic conditions such as irritable bowel syndrome, inflammatory bowel disease, obesity, immune-mediated diseases, metabolic disorders, cancer, infections and even psychological disorders. Hence, in recent years, interest in the role of the intestinal microbiota in health and disease has gained momentum.

Dysbiosis can come about as a consequence of our environment, nutrition, illness, and certain drugs.

Research is advancing our understanding of the environment as a major driver of variability in the microbiome. The orodigestive tract and the respiratory system are major entry pathways for the external environment to impact the human microbiome. Both macroenvironmental factors such as toxins and chemicals, climate change and extreme heat can lead to physiological changes that may favour certain environmental microbiota. The bacterial and fungal communities in the building environment where we inhabit may also be implicated in changes to the microbiota. Socioeconomic factors are considered to impact the microbiome due to limited access to medical and dental care and decreased healthy eating and exercise practices.
In addition, our contributions to our microenvironment, such as smoking, alcohol, diet, and personal hygiene, may all push the balance of the microbiome into a more healthy or less healthy state.

‘Healthy bacteria’ such as Bifidobacteria and Lactobacillus are often less abundant in individuals over 60 years of age and those with chronic conditions such as diabetes, obesity and heart disease. This dysbiosis may leave the gut more susceptible to infections, inflammation, and autoimmune illnesses such as Crohn’s disease and ulcerative colitis.

The frailty of older adults, reduced exercise, chronic conditions, and prescription medications, particularly psychoactive and antihypertensive drugs, heavily influence the gut microbiome. Any dysbiosis can have an impact on the gut-brain axis, a two-way biochemical signalling pathway between the intestinal tract and the central nervous system. Unsurprisingly, there is often a state of dysbiosis in the intestines of patients with Alzheimer’s disease.

The effect of the microbiota on the gut-brain axis is also known to influence mood disorders. It has been observed that individuals with intestinal disorders have a high co-morbidity of depression and anxiety.
Stress is commonly followed by depression and anxiety. However, not all individuals who have experienced stress have subsequent negative emotional consequences and are considered stress-resilient. There is growing evidence that this stress resilience is linked to a favourable balance in the gut microbiota.

Broad-spectrum antibiotics reduce the diversity of the gut microbiota, destroying the pathogen of concern but also the commensal microorganisms. This reshaping of the microbiota in the gut affects immune regulation and metabolic activities, resulting in increased susceptibility to infections with pathogens such as C. difficile. In addition, the overuse of antibiotics has led to a global crisis in antibiotic resistance.

Certain medications affect the gut microbiome, which can metabolise drugs by transforming them into various metabolites. This bidirectional relationship can go some way towards explaining the different responses seen between different individuals to the same drug. This interaction between gut microbes and commonly used non-antibiotic drugs has also gained considerable interest. Drugs such as non-steroidal anti-inflammatories, statins, antipsychotics and painkillers can all alter the gut microbiome. It is thought that up to 25 per cent of all non-antibiotic drugs suppress the growth of at least one bacterium.
Certain drugs, such as metformin, for the treatment of type II diabetes, show an enhanced efficacy when given orally but not when given intravenously, suggesting a critical therapeutic role of the gastrointestinal tract. The side effects of many medications include gastrointestinal symptoms. As such, many clinical trials are underway to investigate the role of drugs in regulating the gut microbiome and improving the efficacy of drugs and biologics.

• Ahn J, Hayes RB. Environmental Influences on the Human Microbiome and Implications for Noncommunicable Disease. Annu Rev Public Health. 2021 Apr 1;42:277-292. doi: 10.1146/annurev-publhealth-012420-105020. PMID: 33798404
• Wan Y, Zuo T. Interplays between drugs and the gut microbiome. Gastroenterol Rep (Oxf). 2022 Apr 8;10:goac009. doi: 10.1093/gastro/goac009. PMID: 35401987
• Patangia DV, Anthony Ryan C, Dempsey E, Paul Ross R, Stanton C. Impact of antibiotics on the human microbiome and consequences for host health. Microbiologyopen. 2022 Feb;11(1):e1260. doi: 10.1002/mbo3.1260. PMID: 35212478