COVID-19- Correlation with Indian Diet and Gut Microbiome

Interdependence between the host and gut microbiota has been found to be indispensable (2) . The impact of gut microflora can broadly be classified into structural, metabolic, and protective functions. It helps to strengthen the gut barrier by enhancing expression of tight junction proteins and simultaneously inducing Immunoglobulin (IgA) production. The prominent bacteria that aid in this activity include Bacteroides spp., F. prausnitzii, Akkermansia, muciniphila, Roseburia spp, etc. and

probiotic strains including Bifidobacterium and Lactobacillus spp. (3) . The metabolic functions form their ability to produce essential vitamins and simultaneously metabolize iron, along with fermentation of non-digestible carbohydrates. The indigenous microflora also protects the host by preventing the establishment of gut pathogens due to enhanced competitive binding by competing for nutrients, space, and host cell receptors along with the production of various anti-microbial factors, in turn resulting in pathogen displacement (4) .

The fermentation of dietary fiber by gut microbes results in formation of short-chain fatty acids, which have been further known to regulate immune responses via various receptors and pathways involving molecules such as G-protein coupled receptors (GPCRs). GPCRs such as GPCR43 and GPCR120 have been reported to regulate anti-inflammatory pathways (5)

Plant-based rich fiber diet, which happens to be consumed by a majority of the Indian population, appears to be advantageous. It helps to replenish the host gut microbiota with beneficial microbes thereby leading to a symbiotic association conferring various health benefits to the host including enhanced immunity. Besides, chronic gut inflammation has been suggested to result from specific aberrations in gut microbiome constitution, the latter holds the opportunity to be regulated by diet.

Indian Government announced the lockdown on March 25, 2020, further followed by three more lockdowns. Lockdown implementation proved to be a reasonably effective strategy, as by the end of the 4 th lockdown on 31 st May 2020, the total number of reported infection cases in India were 182,143 with 5164 deceased. (6) This implies, on average, only 12 infected cases per lakh people were seen during the lockdown period. Here, it may be inferred that plant-based, home-cooked, rich fiber diet consumed by the Indian population during lockdown, could be one of the plausible reasons that might have resulted in generation of symbiotic microflora, thereby eliciting anti-inflammatory responses.

Further during the lockdown period, several of the daily wagers including migrant workers faced adversity and underwent phases of forced starvation. This situation is comparable to intermittent fasting (IF) conditions. In this context, it can be speculated that it might have given then the advantage to this subset of the population by enriching their beneficial gut microbiota, thus, assisting the microbiome immune axis. It may be noted that perhaps, deaths that occurred amongst migrants were due to road accidents or starvation but not due to SARS-CoV-2 infection.

On the other hand, quarantine had been reported to induce stress which leads to 'stress eating' wherein individuals tend to increasingly consume food containing high fat and sugar, thus leading to obesity. Obese individuals are reported to possess a decreased immune function demonstrated by a deficit in CD8+ T cells responses used to combat viral infections. This could have possibly influenced higher mortality outcomes due to increased viral load, coupled with pulmonary pathology (7)

Indian diet is rich in whole grains – a key source of dietary fiber, carbohydrates, resistant starch, and oligosaccharides. These nutrients are fermented in the colon after digestion in the small intestine and result in the production of short-chain fatty acids (SCFAs). These act as an energy reservoir for colonocytes, lower the colonic pH, eliciting a healthy immune response beyond the gut (8).

The state-wise data distribution within India presented that in the states where millet is the staple food, less prevalence of COVID-19 infections was observed along with a higher recovery rate, and lower fatality rate.

It is noteworthy that despite having many cases, India was spared from a high incidence of fatality caused by SARS-CoV-2 as compared to other western countries. USA and Brazil have maximum number of cases followed by European countries. Both these regions consume meat-rich diet and saturated fatty acids in their diet. Pro-inflammatory responses triggered due to such a diet may lead to fatal complications in patients infected with COVID-19, where lung epithelial cell inflammation might have detrimental consequences.

It seems rational that detrimental outcomes in COVID-19 could be possibly mitigated if a person is accustomed to a healthy diet or diet supplemented with healthy microbes such as probiotics (9) .

The implementation of lockdown which had proven to be a promising non-pharmacological measure seems to have resulted in the consumption of a home-cooked healthy diet, thereby enriching the beneficial microflora in the gut, which might have resulted in better prognosis of COVID-19 patients in India in comparison to that observed in the western countries. (1)

Probiotics are effective in improving mucosal immunity and could help to enhance intestinal and lung barrier and homeostasis, by increasing the activity of regulatory T cells, ameliorating anti-viral defenses, reducing pro-inflammatory cytokines in respiratory and systemic infections. (10)

While the recommendations regarding the strain, dose, and duration of probiotic remain to be well- defined; the large experience of clinical usage and evidence for beneficial effects in various clinical settings suggest that Lactobacillus and Bifidobacterium can safely be considered (11)

Adapted from

1 Rishi P, Thakur K, Vij S, Rishi L, Singh A, Kaur IP, Patel SKS, Lee JK, Kalia VC. Diet, Gut Microbiota and COVID-19. Indian J Microbiol. 2020 Sep 28;60(4):1-10. doi: 10.1007/s12088-020-00908-0. Epub ahead of print. PMID:33012868; PMCID: PMC7521193.

2 Gaur M, Vasudeva A, Singh A, Sharma V, Khurana H, Negi RK, Lee J-K, Kalia VC, Misra R, Singh Y (2019) Comparison of DNA extraction methods for optimal recovery of metagenomic DNA from human and environmental samples. Indian J Microbiol 59:482–489. https://doi.org/10.1007/s12088-019-00832-y

3 Wells JM, Brummer RJ, Derrien M, MacDonald TT, Troost F, Cani PD, Theodorou V, Dekker J, Me´heust A, De Vos WM, Mercenier A (2017) Homeostasis of the gut barrier and potential biomarkers. Am J Physiol Gastrointest Liver Physiol 312:G171– G193. https://doi.org/10.1152/ajpgi.00048.2015

4 Kedia S, Rampal R, Paul J, Ahuja V (2016) Gut microbiome diversity in acute infective and chronic inflammatory gastrointestinal diseases in North India. J Gastroenterol 51:660–671.https://doi.org/10.1007/s00535-016-1193-1

5 Maslowski KM, Mackay CR (2011) Diet, gut microbiota and immune responses. Nat Immunol 12:5–9.https://doi.org/10.1038/ni0111-5

6 World Health Organization (2020) Coronavirus disease (COVID-19) situation report—132, vol 31 – 5

7 Mattioli AV, Sciomer S, Cocchi C, Maffei S, Gallina S (2020) Quarantine during COVID-19 outbreak: changes in diet and physical activity increase the risk of cardiovascular disease. Nutr Metab Cardiovasc Dis.https://doi.org/10.1016/j.numecd.2020.05.020

8 Den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54:2325–2340. https://doi.org/10.1194/jlr.R036012

9 Kumar R, Sood U, Gupta V, Singh M, Scaria J, Lal R (2020a) Recent advancements in the development of modern probiotics for restoring human gut microbiome dysbiosis. Indian J Microbiol 60:12–25.https://doi.org/10.1007/s12088-019-00808-y

10 Benedetta Bottari , Vincenzo Castellone & Erasmo Neviani (2020): Probiotics and Covid-19, International Journal of Food Sciences and Nutrition, DOI:10.1080/09637486.2020.1807475

11 Angurana SK, Bansal A. Probiotics and COVID-19: Think about the link. Br J Nutr. 2020 Sep 14:1-26. doi:10.1017/S000711452000361X. Epub ahead of print. PMID: 32921328