Gut microbiota and Covid-19- possible link and implications

Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. Role of the gut microbiota in influencing lung diseases has been well articulated. It is also known that respiratory virus infection causes perturbations in the gut microbiota. Diet, environmental factors and genetics play an important role in shaping gut microbiota which can influence immunity. Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies.

For more on this please read my review published in the peer reviewed journal - Virus Research

https://www.sciencedirect.com/science/article/pii/S0168170220304603

The lost war or is it? – Infections vs Antibiotics

Antibiotics, once hailed as magic bullets for battling infection are now facing serious challenge from their adversaries, the bacteria, which are hitting back with renewed vengeance. A recent case of a patient in New Zealand dying of bacterial infection (Klebsiella pneumonia) which was resistant to all known antibiotics points to an ‘apocalypse’ scenario in the future if corrective measures are not taken. 

So where is the problem? First, the tendency to overprescribe antibiotics for even slightest of infection is a big worry. Alexander Fleming, the father of antibiotics had warned of dangers of antibiotic resistance. In fact, Penicillin-resistant bacteria arrived while the drug was still being given to only a few patients. Another breeding ground for antibiotic resistant bacteria is in their rampant use in farm animals. Unfortunately, for the pharma companies research interest into antibiotics have slowly waned as there are far more profitable drugs to throw money at, since antibiotics are usually single-serve drugs for humans, not long-term treatments. Drugs for chronic conditions tend to be more profitable. And with drug resistance quickly evolving, rendering older antibiotics ineffective, pharma companies have even less incentive to invest in these drugs. However, recent trends suggest that big pharma companies might be reviewing their strategy as Roche has re-entered the arena through a $550 million tie-up with privately held Polyphor, a Swiss company, to develop and commercialize an experimental antibiotic against hospital superbugs. 

The key is to collaborate with Universities and small drug discovery companies that focus on infections as Roche did. Smaller companies are looking at next-generation drugs or in some cases alternative therapies. Some companies for example are looking at bacteriophage therapy. But despite technical successes, these companies face an uphill battle in developing a consistent, approvable product and haven't yet found much commercial validation or attracted much investment. This is where the experience and backing of big pharma companies would help. Another alternate and a newer area of interest is the human microbiome, which can lead to potential commercial therapeutics. Microbiome companies like Seres Health, Vedanta Biosciences and Second Genome are a good bet as far as making the next cut for coming out with a new approach to treating infections are concerned!

Gut Microbiome – Type 2 diabetes association; outcome and possibilities

The phrase ‘my gut feeling’ has got another scientific validation with some new metagenomics studies published recently. After all, it seems that the gut can dictate the potential well being of an individual. A case in point is the latest paper in Nature journal in which the researchers conducted a gut metagenomic study on Chinese patients suffering from type 2 diabetes (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11450.html). Gut microbiome has been in the forefront of research especially after the advent of the Next Generation Sequencing technology. Today, the advancement in the field of development of sequencers and sequencing technology is even challenging the Moore’s law.

Gut microbiome also being called as the “other genome” or human’s “second genome” is implicated in many of the chronic diseases/disorders like obesity, inflammatory bowel disease and even depression so it is natural that with the latest technology in hand the scientists would focus on this in a much more refined manner. The present study finds some interesting facts about the commensals in the gut of Chinese patients suffering from type 2 diabetes. Functional characterization showed that there was a decrease in the level of bacterial chemotaxis, flagellar assembly, butyrate biosynthesis and metabolism of cofactors and vitamins in the gut bacteria of these patients. The researchers also found markers that indicated that the gut environment of a T2Dpatient is one that stimulates bacterial defence mechanisms against oxidative stress. This might be interesting as previous studies have implicated high oxidative stress levels to pre-disposition to type 2 diabetes. Strikingly, the researchers found orthologue markers that suggest that these diabetic patients might have a hostile gut environment. The researchers also found that there is moderate gut bacteria dysbiosis and an increase in several opportunistic pathogens.

The above mentioned salient outcomes of the study raise many exciting questions and possibilities. Does the change in gut microbiome composition a cause or an effect of the disease? Scientists would be addressing this part next with some studies in animals. Can in the future the gut microbiome sequencing be used as a predictive tool? Can modulating the gut microbiome cure such diseases? Can effective research in pro-biotics now fill in the space and fulfill what modern medicines could not achieve so far?

This is a perfect example of how a 21^st century technology has ignited a fresh look at the association of the microbiome with the human health

Human microbiome – the new frontier in medicine?

‘Antibiotics heal but they also cause damage’- this adage is well known and now probably better understood. With the advent of Next Generation Sequencing (NGS), exploring the world of the micro organisms has become easier. And as they say, ‘truth is stranger than fiction’; the results of such studies are giving some startling facts about the bacteria that co-inhabit our bodies. Like each individual has a unique DNA or fingerprint, it is now being realized that we might have unique microbiome signature!!!!

The microbiota in our body is known to influence our good health. Recent evidence has linked the microbiome with different diseases. In fact, at least one parasitic protozoa - Toxoplasmosis gondii - has been shown to affect behaviour in rats. The protozoa reproduces only in cats, and studies have shown that when mice or rats are infected with it, the protozoan makes them less afraid of cats, and they are, therefore, more likely to be eaten by them.

Understanding microbiome and their interaction not only with their host but also between themselves are giving lot of food for thought in channelling our views of manipulating this micro-ecosystem in our body for desirable results. A case in point here is the role  and benefit of probiotics and as Prof David Relman (one of the pioneers in the field of microbiome research) puts it “The hesitation right now is there aren't a lot of good data. Most clinicians will say, 'I don't personally think it's doing much, but it can't hurt so if you feel better, why not.' I think there may be some real benefits, but I also think we have imprecise probiotic options now. So we're giving these somewhat irrelevant microorganisms to people, and yet they do seem to have some beneficial effects”(source -http://www.sfgate.com/health/article/Sequencing-of-human-microbiome-fills-knowledge-gap-3683156.php)

Therefore now is the right time to make maximum use of the data we derive from studying our microbiota and look at these organisms in a different perspective rather than thinking about them as our “enemies”. Also, I sincerely hope that pharma/biotech and nutraceutical companies collaborate to find better solutions to the diseases that we face today!