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India Currents gave me a voice in days I was very lost. Having my articles selected for publishing was very validating – Shailaja Dixit, Executive Director, Narika, Fremont
Engage! – Discussions on active involvement in personal health and global wellness
Part 1 of this article was published in India Currents in May. It highlighted the establishment and development of the human microbiome through infancy into adulthood and described the role that the environment plays in this. In this article, we explore the many facets of health that the microbiome is involved in.
Sometimes termed the second genome, the idea that microbes are involved in the regulation of our physical health including digestion, cholesterol, and chronic disease may be more intuitive than the possibility that they also play a role in modulating mood, stress response, and psychiatric conditions. While these studies include those performed in the laboratory as well as the field, they serve the practical goals of initially understanding the mechanisms by which microbes interact with human physiology, and secondly the conversion of this knowledge into human therapeutics.
Microbiome effects on gastrointestinal (GI) health are not surprising. As an example, scientists sequenced the microbiome (including bacteria-bacteriome, viruses- virome, and antibiotic-resistant bacteria- resistome) of urban and rural/tribal populations around Nagpur, India, and found distinct associations of bacterial species with individuals suffering from diarrhea and those that were normal. This included Clostridium difficile (C. diff) which can cause symptoms ranging from diarrhea to inflammation of the colon. Diarrhea was associated with a move to urban locales and with environmental changes such as antibiotic use.
Bacterial species associated with good GI health seemed to cross cultures, and the same species were also reported in studies conducted in Africa, the Americas, and Mongolia, providing impetus to use this knowledge to promote GI health and function.
As mentioned in Part 1, chronic diseases such as diabetes and obesity are associated with urban microbiome profiles. While most of these studies analyze fecal samples to study disease demographics, others have focused on vaginal health. Just as in the gut, there is an optimal microbiome in the skin at this site that serves a protective function. Dysbiosis (disruption of microbial communities) causes susceptibility to other infections including sexually transmitted diseases and AIDS.
These direct effects of the microbiome arise from the manipulation of resident populations and out-competition by unwanted organisms. Longer range effects are also seen on distant organs resulting in physiological disturbances that contribute to disease.
Fascinating studies of the soluble molecules and alkaloids that the microbes secrete are ongoing, along with their effects on local and distant cells. The so-called gut-brain axis is a prime example of this. The stress response is primal and important for survival and is mediated by a well-studied pathway involving the hypothalamus-pituitary-adrenal gland. It is also thought to be involved in stress-related diseases such as anxiety and depression. Several studies, including a pioneering Japanese study, have shown that microbiota in the gut influence this pathway in a way that affects behavior, possibly at the very basic level of regulating neurotransmitters in the brain. The link between autism and GI problems is well known, and other studies have suggested that gut microbiota may be involved in Parkinson’s disease, and even in the regulation of mood and personality.
Cancer also seems to have several potential dependencies on microbes. The best known is cervical cancer which is commonly caused by human papillomavirus infection. More recently a bacterial species have been found associated with colorectal cancer, and may be implicated in the growth and spread of these tumors, and other gut bacteria create conditions in the large intestine that are more conducive to cancer growth. About 700 species occupy the oral cavity, and some of them are thought to influence head and neck cancers, and also other GI tumors. Microbiota are known to alter the immune response to a tumor, and on the flip side, dysbiosis of the oral microbiome is seen in several GI cancers, and this could become a tool for early detection of these cancers.
The microbiome is known to change with age, and this aging microbiome could contribute to cardiac insufficiencies seen with age. The maintenance of biodiversity along with regular exercise is thought to slow the aging process. Other studies suggest that microbes influence basic physiological processes such as inflammation and immune reactions that underlie such manifestations as bone loss and allergies. In fact, these broader effects may be orchestrated by the microbiome that colonizes a human at infancy, and which plays a role in instructing the body on how to recognize ‘self’ from ‘non-self’ and react to the environment.
As one can imagine dissecting these complex interactions is very nuanced, and is a work in progress. Thus, therapeutic interventions that are currently being explored may seem unsophisticated, although they have provided relief. Fecal transplants are being explored with some success for the treatment of recurrent C. diff infections, and more experimentally for inflammatory bowel disease and immune dysregulations. The idea behind this approach is that the re-introduction of microbial diversity, when this has been compromised, restores a healthy microbiome. Here encapsulated fecal material from healthy individuals is administered orally to patients, or transplanted directly into the colon. More recently, fecal transplants have been shown to improve the efficacy of cancer immunotherapy treatments. Although donors are extensively investigated for their own microbial flora among other medical tests, and recipients closely monitored, these therapies are considered experimental and are administered when tested treatments have not produced results.
Information about the balanced existence of human microbiota including bacteria, viruses, protozoans, bacteriophages (viruses that attack bacteria), and even parasites continue to emerge. While we are still learning the complexities of this dynamic organ, we can proactively work towards maintaining it, in the same way that we try and maintain good heart health. Regulation of diet and the conscious incorporation of pre- and probiotic foods is an easy start. Prebiotics are comprised of indigestible fiber and are present in fruits, vegetables, and whole-grain, and are important for the growth and maintenance of the gut microbiome. Probiotics are fermented foods that contain beneficial microorganisms and include yogurt, kimchi, and tempeh. The incorporation of spices such as turmeric, black pepper, and ginger have the ability to modulate gut communities and gut health. Ayurveda follows a holistic approach to optimal health, and maintenance of a healthy microbiome is an integral part of this. Understanding its relevance in terms of the doshas (vata, pitha and kapha) is one approach, and so is its modulation by diet, sleep, exercise, and regular purging of the bowels.
A recent mega-study conducted across 60 cities in 6 continents over 3 years studied the ‘urban microbiome’ and identified thousands of as yet unidentified species of bacteria and viruses in mass-transit systems. While there may be several practical uses for such an atlas, it gives credence to the concept of madi that was, and probably still is, followed in orthodox South Indian families, where extreme importance is given to cleanliness in terms of both personal hygiene and the home, combined with strict observance of dietary regulations. At a personal level, the rigorous COVID-related cleanliness regimens that I am currently following are very much in line with this!
Good and bad microbes exist, and we need to nurture the ones that are necessary and be cautious of the rest. Our co-evolution with these ancient organisms has a design, and while their empirical value was recognized by ancient systems of medicine including Ayurveda, we are still unraveling the details of their complexities.
L.Iyengar has lived and worked in India and the USA. A scientist by training, she enjoys experiencing diverse cultures and ideas, and writing. Her short story will be included in an anthology showcasing a group of international women writers, to be published in 2021 by The Nasiona. She can be found on Twitter at @l_iyengar. www.liyengar.com