COVID-19 infection affects faecal microbiota, may persist long after recovery

COVID-19 infection is associated with faecal microbiota dysbiosis*, especially those that cause more severe disease, says a prominent researcher. However, there is ambiguity as to whether it is a meaningful association or an epiphenomenon**.

Speaking at the recent Malaysian Society of Gastroenterology and Hepatology Annual Scientific Meeting (GUT) 2022, Professor Dr Uday C Ghoshal, head of Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, said that SARS-CoV-2 is a respiratory virus with severe infectivity, and hospitalization is often accompanied by treatment with a broad range of drugs that include antibiotics and steroids.

Therefore, the cause of this dysbiosis may not be entirely related to the disease, but rather an epiphenomenon—caused by factors such as hospitalization, antibiotic use, loss of control over comorbidities (eg, diabetes), change in diet and route of administration (ie, nasogastric feeding), and alteration in gut mobility.

As there are so many confounders that affect gut microbiota, the jury is currently still out as to whether faecal microbiota dysbiosis is a direct consequence of COVID-19 infection or an epiphenomenon. Faecal microbiota dysbiosis may also persist long after recovery from COVID-19.

One method to improve gut microbiota dysbiosis is by dietary interventions, either consumption of probiotics or prebiotics. [J Funct Foods 2021;87:104850] Gut microbiota diversity is important as high diversity has been linked to better health while lower gut microbiota diversity is associated with poor health. Dysbiosis skews the body towards colonization by opportunistic pathogens and proinflammatory state. Conversely, a balanced microbiota reduces inflammation of the gut, improving the gut barrier and reduces translocation of bacteria and toxins into the blood. [Gastroenterology 2022;162(1):9–16]

Uday brought up the possibility of targeting the gut microbiota to correct gut microbiota dysbiosis as one of the means of attenuating COVID-19 infection or enhancing vaccination efficacy. While research is ongoing, existing studies point to this possibility. A gut-microbiota derived symbiotic formula produced by the Chinese University of Hong Kong has demonstrated in a pilot study, that the product effectively “hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalized COVID-19 patients.” [J Gastroenterol Hepatol 2022;37:823–831]

Could the hygiene hypothesis explain why some countries were less affected by COVID-19?
Uday put forward the idea that some countries such as India, traditionally considered as a “less hygienic” place, suffered less serious adverse events as their microbiome were more diverse. [Clin Transl Gastroenterol 2020;11(12):e00259] In fact, while media reported increased casualties due to COVID-19 infection, the increase in risk of rhino-orbito-cerebral mucormycosis was due largely to hyperglycaemia and steroid overuse and not due to the viral infection itself. [PLoS One 2022;17(8):e0272042]

Bacteria found in stools do not represent the full spectrum of gut microbiome, said Uday. “Bacteria in stools only represent those found in the colonic region. We keep doing studies on stool because it is the easiest to obtain.” Furthermore, many bacteria found in the gut are difficult, almost impossible to culture effectively outside of the body. However, the advent of next generation sequencing (NGS)^# has allowed better understanding and elucidation of the microbiome.

* Dysbiosis - any condition where gut microorganisms are abnormal in number or altered in quality or location.

**epiphenomenon —a secondary symptom, occurring simultaneously with a disease but not necessarily related to it.

^# NGS - is a genetic sequencing technology used to determine the order of nucleotides in entire genomes or targeted regions of DNA or RNA.