In a recent study published in the Clinical Nutrition Journal, researchers determined the association between the gut microbiome and diet with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection outcomes.

Study: Association of Gut microbiota and Dietary component intake with COVID-19: A Mendelian randomization study. Image Credit: ChristophBurgstedt/Shutterstock.com

Background

The coronavirus disease 2019 (COVID-19) has resulted in unusual morbidity and mortality across the globe. Given the scarcity of medications specifically designed to treat SARS-CoV-2 infections, understanding risk factors linked with COVID-19 susceptibility and severity is critical to preventing and managing COVID-19 and lowering its global burden.

Recently published observational-type studies have revealed that the intestinal microbiota of SARS-CoV-2-positive individuals is significantly altered.

Furthermore, accumulating evidence indicates optimum nutrition may help prevent and mitigate COVID-19. Nonetheless, data on the causative effect of the intestinal microbiome and diet on COVID-19 risk are limited.

About the study

The present study estimated the intestinal microbiome's and diet's causality on COVID-19 susceptibility and severity.

The team performed Mendelian randomization (MR) genetic analysis, including genomic variants as instrumental variables for the gut microbiome, dietary intake, and SARS-CoV-2 infections.

For the study, 18,340 individuals were recruited from 24 groups, mainly Europeans (132,266 individuals), with 211 taxa (131, 35, 20, 16, and nine genera, families, orders, classes, and phyla, respectively).

The researchers obtained summary statistical data for intestinal microbiome and COVID-19-associated phenotypes from previously published and publicly accessible genome-wide association studies (GWAS) organized by the international MiBioGen (microbiome genome) consortium and the SARS-CoV-2 infection Host Genetics Initiative (HGI, fifth release), respectively.

Three COVID-19-associated phenotypes were derived: SARS-CoV-2 infection (38,984 and 1,644,784 COVID-19 cases and controls, respectively); severe SARS-CoV-2 infection (5,101 and 1,383,241 COVID-19 cases and controls, respectively); and SARS-CoV-2 infection requiring hospitalization (3,159 and 7,206 covid-19 cases and controls, respectively).

Summary-level dietary information was extracted from the Medical Research Council's (MRC) Integrative Epidemiology Unit at the University of Bristol's (IEU) second analysis in the United Kingdom (UK) Biobank.

Dietary phenotypes, inclusive of the intake of alcohol, water, tea, coffee, cereals, bread, processed meat, pork, poultry, mutton, oily and non-oily fish, beef, fresh fruits, raw vegetables, cheese, salt, and the type of milk consumed, were used.

The gut microbiome was profiled by targeting three variable sites of the 16S ribosomal ribonucleic acid (rRNA) gene.

Single nucleotide polymorphisms (SNPs) related to the study exposure with genome-level significance were selected as instrumental variants (IVs).

The inverse-variance weighted (IVW) approach was used to estimate causality, and random- and fixed-effects modeling was performed for heterogeneous and homogeneous data analysis, respectively, to determine the odds ratios (ORs).

Results

Ruminococcustorques significantly lowered the risk of SARS-CoV-2 infection (odds ratio 0.5). Ruminococcaceae UCG013 potentially increased COVID-19 risk (odds ratio 1.4), whereas Ruminococcus1 potentially lowered the risk (odds ratio _FE 0.7).

In addition, Ruminococcustorques (odds ratio 0.2) and Bifidobacteriales (odds ratio 0.5] were potentially linked to a lowered severe SARS-CoV-2 infection risk.

On the contrary, Bifidobacteriaceae (odds ratio 2.1), Tyzzerella3 (odds ratio _FE 2.2), and Actinobacteria (odds ratio 2.5) were potentially related to an elevated severe SARS-CoV-2 infection risk. Bifidobacteriaceae (odds ratio _RE 2.1), Tyzzerella3 (odds ratio 2.2), and Actinobacteria (odds ratio 2.5) potentially increased the severe SARS-CoV-2 infection risk.

A suggestive link between SARS-CoV-2 infection and higher Victivallis counts (odds ratio 2.0). In addition, genetically estimated severe SARS-CoV-2 infections were significantly related to higher Turicibacter counts (odds ratio 1.1) and lower Olsenella counts (odds ratio 0.9).

Severe SARS-CoV-2 infection was potentially linked to elevated Ruminococcus1 counts (odds ratio 1.1) and reduced CandidatusSoleaferrea (odds ratio random effects 0.9) and Parasutterella counts (odds ratio 0.9).

Concerning dietary intake, processed meat consumption increased COVID-19 risk significantly (odds ratio 1.7). The findings indicated that consuming beef increased COVID-19 risk (odds ratio 2.0), whereas fresh fruit consumption (odds ratio 0.3) lowered severe SARS-CoV-2 infection risk.

Further, adding salt to foods (odds ratio 1.9) potentially elevated the severe SARS-CoV-2 infection risk. The supplementary analyses yielded similar findings without significant heterogeneities or horizontal pleiotropy in the sensitivity analyses.

Conclusions

Overall, the study findings supported the intestinal microbiome's and diet's causal effects on SARS-CoV-2 infections.

The counts of microbes belonging to genera such as Ruminococcustorques, Ruminococcaceae UCG013, Ruminococcus1, Tyzzerella3, order Bifidobacteriaceae, Bifidobacteriales, and class Actinobacteria might enhance COVID-19 susceptibility as well as severity.

In addition, consuming processed meat, beef, fresh fruits, and added salt may impact the risk and severity of SARS-CoV-2 infections. The reverse effects of SARS-CoV-2 infections on gut microbial alterations were also observed.

SARS-CoV-2 infections may alter the intestinal counts of Oscillospira, Lachnospira, Victivallis, RuminococcaceaeUCG009, Olsenella, Turicibacter, Parasutterella, CandidatusSoleaferrea, and Ruminococcus1 genera.

Journal reference:

• Zhang H & Zhou Z, (2023)., Association of Gut microbiota and Dietary component intake with COVID-19：A Mendelian randomization study., Clinical Nutrition., doi: 10.1016/ j.clnu.2023.06.017. https://www.clinicalnutritionjournal.com/article/S0261-5614(23)00203-0/fulltext