MARKED CHANGES ARE SEEN IN THE SMALL BOWEL MICROBIOME AS A RESULT OF THE COVID-19 PANDEMIC

ABSTRACT

SARS-CoV-2 has had a profound impact on the human population in the last 24 months. This includes dramatic changes in lifestyle, hygiene, and altered food sources/consumption patterns, which could directly impact the small bowel microbiome on an individual and perhaps even at a population level. To date, this has not been examined. Here, we compare small bowel microbial profiles in subjects before SARS-CoV-2 and intra-pandemic. Methods: The REIMAGINE study is a large-scale study using validated methods for duodenal aspirate collection and microbiome sequencing in subjects undergoing upper endoscopy. Subjects were divided into 2 groups pre-pandemic, from February 2019 to March 2020;and intrapandemic, from April 2021 to September 2021. Groups were matched for gender, age, and BMI. Duodenal aspirates were collected, and microbial DNA was isolated using the MagAttract PowerSoilDNA Kit. V3 and V4 libraries were sequenced on a MiSeq. Reference-based Operational Taxonomic Unit clustering was performed using SILVA v132 database. Taxonomic analysis was performed with CLC Microbial Genomics Module v.2.5 and MicrobiomeAnalyst, and duodenal microbial alpha- and beta-diversity indices were calculated. Significance was determined by Wilcox test. Results: In total 94 subjects were included in the analysis. The overall duodenal microbiome profile (beta-diversity) of intra-pandemic subjects (n=38, mean age= 51 ± 18, mean BMI =23.9 ± 4.7) was significantly different from pre-pandemic subjects (n=56, mean age= 51 ± 15, mean BMI = 25.24 ± 4.9)(p<0.002, Fig1A), with no significant changes in duodenal microbial alpha diversity between groups (Fig1B). Significant duodenal microbial taxonomic differences were identified between groups, including changes in the relative abundance (RA) of 2 phyla, 3 classes, 6 orders, 4 families and 23 genera (Fig2A). At the phylum level, Actinobacteria RA was significantly decreased in the intra vs. the pre group (FC=-1.99, P=9.83E-8, Fig2B). Additionally, at the genus level, RA of Rothia (P= 6.85E-7), Pseudomonas (P=0.0376), and Escherichia (P=0.0092) were significantly decreased in the intra group (Fig2A). Of note, the phylum Deinococcus (P=0.0016) was increased in the intra vs. the pre group (Fig2B). Conclusion: In this first study examining the effect of the COVID-19 pandemic on the small bowel microbiome, we show substantial changes in microbial profiles intra-pandemic as compared to pre-pandemic. The duodenal microbiome of intra-pandemic subjects was associated with less disrupter bacteria (Escherichia and Pseudomonas), commonly associated with GI disorders. In contrast, Deinococcus phylum was increased intra-pandemic. This phylum includes organisms resistant to sanitation and increased in the nasal passage of people during the pandemic. The short and long term impact of these changes on human health require further study.(Figure Presented)