The microbiome: A delicate community

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    The understanding of the gut microbiome is evolving year on year and its importance is becoming more obvious. The human gut microbiota can weigh up to 2kg and contain trillions of microorganisms with a microbiome of more than three million genes combined. The scale of importance of the microbiota means that it has become classified as a new organ of the body that has been shown to have a wide variety of roles including nutrition, metabolism, pathogen resistance, and regulation of the immune response.

    However, the microbiota is a delicate community that can be affected by a range of factors like host genome, diet, age, geography, mode of birth and antibiotics. So what happens when it goes wrong?

    Changes in the gut microbiome can influence the development of diseases, ranging from gastrointestinal disorders to metabolic disease. This can be expected as it seems very reasonable that dysbiosis in the gut would affect gut health. Interestingly, the gut microbiome has been shown to have profound effects on neurological disorders. There are neurons that link the brain to the gut and monitor its composition, and therefore changes in the microbiota have been shown to influence behaviour and mental health. The microbiota can also influence disorders ranging from Alzheimer’s, autism spectrum disorder, MS, Parkinson’s, and stroke. 

    Alzheimer’s research receives a vast amount of funding, but there remains a limited understanding of how it is caused and how to treat it effectively. The effect of the gut microbiota provides a new angle for Alzheimer’s research. This disease is characterised by plaques in the cerebral cortex made from an accumulation of misfolded amyloid-β fibrils and neurofibrillary tangles. Research has shown that high-fat and high-calorie diets seem to be a risk factor for Alzheimer’s development, whilst diets high in omega 3 polyunsaturated fatty acids can lower the risk. The microbiota is involved in the absorption and metabolism of omega 3 polyunsaturated fatty acids and it has been shown that Alzheimer’s patients often have low levels of DHA, a type of omega 3, suggesting patients may have a difference in their gut microbiota. Moreover, it has been reported that drinking 3-5 cups of coffee a day can decrease the risk of Alzheimer’s by 65%, compared to drinking less than two cups per day, due to the antioxidant polyphenols found in coffee. Whilst diet clearly affects the microbiota and, therefore, the susceptibility to Alzheimer’s, the microbiota can also affect the brain directly. Changes in the microbiota can cause activation of pro-inflammatory cytokines and consequently increase intestinal permeability, allowing bacteria to breach the gut barrier. This explains why autopsies of brains of patients have been found to have Chlamydia pneumoniae. These are just a few examples of how the microbiome can affect the susceptibility to and severity of Alzheimer’s disease.

    Since the microbiome has massive implications on host health, what is being done to treat it when it goes wrong?

    The most common way to selectively modify or enhance the microbiome is through the use of probiotics, which involves introducing selected bacteria into the gut. However, sometimes these are not enough to resolve large shifts in the microbiota. In this case, faecal transplants are often used, which involves transplanting faeces from a healthy donor to another person. This treatment originated in ancient Chinese medicine more than 1700 years ago, and involved drinking a liquid suspension of the persons faeces, although this practice was (unsurprisingly) risky. Today, faecal transplants are sterile and safe, and are administered by a colonoscopy.

    This has, however, been known to go wrong. A mother obtained a severe intestinal infection and to treat it she received antibiotics that wiped out her whole gut microbiota. Consequently, she required a faecal transplant. Her daughter seemed like a fitting donor as she lived in the same house and had a similar diet; however, the mother put on an excessive amount of weight after the transplant and subsequently sued the hospital for making her fat. This occurred as a result of the faecal transplant containing bacteria that were able to extract nutrients from food very efficiently and so the lack of bacteria in her stomach meant these bacteria colonised very quickly, explaining the rapid weight gain.

    This shows how faecal transplants must be carefully matched!

     

    Photo: https://www.neurologyadvisor.com/conference-highlights/actrims-forum-2020/pediatric-onset-multiple-sclerosis-gut-microbiota-and-relapse-risk/