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ABSTRACT Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting. To address this knowledge gap, we longitudinally sampled 14 SARS-CoV-2-positive subjects who remained outpatient and 4 household controls. SARS-CoV-2 cases exhibited a significantly less stable gut microbiota relative to controls. These results were confirmed and extended in the K18-humanized angiotensin-converting enzyme 2 mouse model, which is susceptible to SARS-CoV-2 infection. All of the tested SARS-CoV-2 variants significantly disrupted the mouse gut microbiota, including USA-WA1/2020 (the original variant detected in the USA), Delta, and Omicron. Surprisingly, despite the fact that the Omicron variant caused the least severe symptoms in mice, it destabilized the gut microbiota and led to a significant depletion in Akkermansia muciniphila. Furthermore, exposure of wild-type C57BL/6J mice to SARS-CoV-2 disrupted the gut microbiota in the absence of severe lung pathology. IMPORTANCE Taken together, our results demonstrate that even mild cases of SARS-CoV-2 can disrupt gut microbial ecology. Our findings in non-hospitalized individuals are consistent with studies of hospitalized patients, in that reproducible shifts in gut microbial taxonomic abundance in response to SARS-CoV-2 have been difficult to identify. Instead, we report a long-lasting instability in the gut microbiota. Surprisingly, our mouse experiments revealed an impact of the Omicron variant, despite producing the least severe symptoms in genetically susceptible mice, suggesting that despite the continued evolution of SARS-CoV-2, it has retained its ability to perturb the intestinal mucosa. These results will hopefully renew efforts to study the mechanisms through which Omicron and future SARS-CoV-2 variants alter gastrointestinal physiology, while also considering the potentially broad consequences of SARS-CoV-2-induced microbiota instability for host health and disease.

ABSTRACT Exposure to environmental toxins is a 21st century global health problem that is often the result of dietary intake. Although efforts are made to reduce dietary toxin levels, they are often unsuccessful, warranting research into novel methods to reduce host exposure. Food-grade microbes that can be delivered to the gastrointestinal tract and that are capable of sequestering toxins present a safe and cost-effective intervention. We sought to investigate the potential for probiotic-supplemented yogurt to lower heavy metal levels in at-risk populations of pregnant women and in children in Mwanza, Tanzania, and to examine the microbiome in relation to toxin levels. Two populations suspected to have high toxic metal exposures were studied. A group of 44 school-aged children was followed over 25 days, and 60 pregnant women were followed over their last two trimesters until birth. A yogurt containing 1010 CFU Lactobacillus rhamnosus GR-1 per 250 g was administered, while control groups received either whole milk or no intervention. Changes in blood metal levels were assessed, and the gut microbiomes of the children were profiled by analyzing 16S rRNA sequencing via the Ion Torrent platform. The children and pregnant women in the study were found to have elevated blood levels of lead and mercury compared to age- and sex-matched Canadians. Consumption of probiotic yogurt had a protective effect against further increases in mercury (3.2 nmol/liter; P = 0.035) and arsenic (2.3 nmol/liter; P = 0.011) blood levels in the pregnant women, but this trend was not statistically significant in the children. Elevated blood lead was associated with increases in Succinivibrionaceae and Gammaproteobacteria relative abundance levels in stool. IMPORTANCE Probiotic food produced locally represents a nutritious and affordable means for people in some developing countries to counter exposures to toxic metals. Further research and field trials are warranted to explore this approach in countries where communities are located near mining sites and agricultural areas, two types of areas where toxins are likely to be elevated.