Hong Kong scientists point to a series of changes in the gut microbiome of patients with post-acute COVID-19 syndrome (PACS) that are linked to respiratory and neuropsychiatric symptoms characteristic of the condition.
Conversely, the presence of butyrate-producing bacteria implies the potential beneficial roles of these microorganisms in reducing systemic complications after the acute infection.
Commenting on the findings, Dr David Strain, Chair of BMA Board of Science and Clinical senior lecturer and honorary consultant at the University of Exeter Medical School, says: “If confirmed in a European/UK population it does offer a very promising area of study.
“The modification of the gut microbiome is feasible with dietary modification with supplements, indeed there have been attempts to treat other conditions (with varying degrees of success) through these methods.”
Amitava Banerjee, Professor of Clinical Data Science at University College London, who was not involved in the study adds: “In this novel study of 106 people with Long Covid in Hong Kong, three-quarters had persistent symptoms at six months.
“The authors found that alterations in the gut microbiome were clearly associated with Long Covid.
“There are important implications for future research regarding the mechanisms of disease underlying Long Covid which have tended to ignore the gastrointestinal system, and also for trials of potential therapies and diagnostic approaches.”
The team from The Chinese University of Hong Kong, conducted a prospective study of 106 patients with a spectrum of COVID-19 severity These patients were followed up from admission to six months and 68 non-COVID-19 controls.
They then analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing and correlated the results with persistent symptoms at six months.
Findings revealed at six months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss.
Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls.
Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii.
Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii.
Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at six months.
“F. prausnitzii depleted in patients with PACS is known to have immunomodulatory properties and can contribute to host defence, including downregulating inflammatory responses,” the study states.
“Different Firmicutes bacteria have diverse roles in upregulating or downregulating ACE2 expression in the murine gut and F. prausnitzii-derived molecule correlated with the capacity to induce anti-inflammatory proteins.”
“Loss of several symbionts, including the genera Bifidobacteria, Roseburia and Faecalibacteria known to have immunomodulatory functions, were especially associated with persistent symptoms among recovered patients with COVID-19.
According to the team, the last two bacteria are important several short-chain fatty acid producers and major players in maintenance of immune homeostasis.
Dr Strain adds: “This finding is consistent with hypotheses that Long Covid may be associated with a small quantity of residual virus in the immuno-privileged tissue (i.e the regions of the body such as the gut, that the protection of our antibodies doesn’t reach).
“It is important to clarify that there are some substantial potential confounders in this study. Notably that this is in a Hong Kong population that have a significantly different diet to the UK population and are have been demonstrated to have substantial differences in their dominant gut species. Further these are observational data.
“We know that in the setting of fatigue, brain fog and the other non-specific symptoms of long COVID, diet changes with an (often inappropriate) shift towards higher energy food in the hope that it will help tackle the debilitating symptoms.
“These dietary changes also come with a change in the dominant components of the microbiome, therefore it is possible that this simply represents the reactive changes to post-acute Covid syndrome.”
Published online: doi.org/10.1136/gutjnl-2021-325989
“Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome”
Authors: Qin Liu et al.