Biology subjects

Cowley, E. S.

Publications and source records attributed to Cowley, E. S..

4 recordsLinked to original sources

bioRxiv2023

Determinants of Gastrointestinal Group B Streptococcus Carriage in Adults

BackgroundStreptococcus agalactiae (Group B Streptococcus, GBS) is a commensal Gram-positive bacterium found in the human gastrointestinal and urogenital tracts. Much of what is known about GBS relates to the diseases it causes in pregnant people and neonates. However, GBS is a common cause of disease in the general population with 90% of GBS mortality occurring in non-pregnant people. There are limited data about the predisposing factors for GBS and the reservoirs in the body. To gain an understanding of the determinants of gastrointestinal GBS carriage, we used stool samples and associated metadata to determine the prevalence and abundance of GBS in the gut microbiome of adults and find risk factors for GBS status. MethodsWe used 754 stool samples collected from adults in Wisconsin from 2016-2017 to test for the prevalence and abundance of GBS using a Taqman probe-based qPCR assay targeting two GBS-specific genes: cfp and sip. We compared the microbiome compositions of the stool samples by GBS status using 16S rRNA analysis. We compared associations with GBS status and 557 survey variables collected during sample acquisition (demographics, diet, overall health, and reproductive health) using univariate and multivariate analyses. ResultsWe found 137/754 (18%) of participants had detectable GBS in their stool samples with a median abundance of 104 copies per nanogram of starting DNA. There was no difference in GBS status or abundance based on gender. Beta-diversity, Bray-Curtis and Unweighted UniFrac, was significantly different based on carrier status of the participant. Prior to p-value correction, 59/557 (10.6%) survey variables were significantly associated with GBS carrier status and 11/547 (2.0%) variables were significantly associated with abundance (p-value<0.05). After p-value correction, 2/547 (0.4%) variables were associated with GBS abundance: an increased abundance of GBS was associated with a decreased frequency since last dental checkup (p<0.001) and last dental cleaning (p<0.001). Increased GBS abundance was significantly associated with increased frequency of iron consumption (p=0.007) after p-value correction in multivariate models. ConclusionsGBS is found in stool samples from adults in Wisconsin at similar frequencies as pregnant individuals screened with rectovaginal swabs. We did not find associations between risk factors historically associated with GBS in pregnant people, suggesting that risk factors for GBS carriage in pregnancy may differ from those in the general population. We found that frequency of iron consumption and dental hygiene are risk factors for GBS carriage in Wisconsin adults. Given that these variables were not assayed in previous GBS surveys, it is possible they also influence carriage in pregnant people. Taken together, this work serves as a foundation for future work in developing approaches to decrease GBS abundance in carriers.

microbiology↗

bioRxiv2022

Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes

The gut microbiome of vertebrates is capable of numerous biotransformations of bile acids, which are responsible for intestinal lipid digestion and function as key nutrient-signaling molecules. The human liver produces bile acids from cholesterol predominantly in the A/B-trans orientation in which the sterol rings are "kinked", as well as small quantities of A/B-cis oriented "flat" stereoisomers known as "primary allo-bile acids". While the complex multi-step bile acid 7-dehydroxylation pathway has been well-studied for conversion of "kinked" primary bile acids such as cholic acid (CA) and chenodeoxycholic acid (CDCA) to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively, the enzymatic basis for the formation of "flat" stereoisomers allo-deoxycholic acid (allo-DCA) and allo-lithocholic acid (allo-LCA) by Firmicutes has remained unsolved for three decades. Here, we present a novel mechanism by which Firmicutes generate the "flat" bile acids allo-DCA and allo-LCA. The BaiA1 was shown to catalyze the final reduction from 3-oxo-allo-DCA to allo-DCA and 3-oxo-allo-LCA to allo-LCA. Phylogenetic and metagenomic analyses of human stool samples indicate that BaiP and BaiJ are encoded only in Firmicutes and differ from membrane-associated bile acid 5-reductases recently reported in Bacteroidetes that indirectly generate allo-LCA from 3-oxo-{Delta}4-LCA. We further map the distribution of baiP and baiJ among Firmicutes in human metagenomes, demonstrating an increased abundance of the two genes in colorectal cancer (CRC) patients relative to healthy individuals. SIGNIFICANCE STATEMENTBile acid synthesis by vertebrates is central to digestion and nutrient signaling. Gut bacteria have evolved enzymes capable of converting primary bile acids to hundreds of secondary bile acids. While bile acid microbiology has been focused on the metabolism of ring hydroxyl groups and the carboxylated side-chain, very little is known about how bacteria alter the shape of the steroid ring system. Here, we describe enzymes expressed by Firmicutes that convert the "kinked" primary bile acid into "flat" secondary bile acids. Decades of research indicate that increased levels of secondary bile acids are risk factors for colorectal cancer. Hidden Markov Models developed from the BaiP and BaiJ enzyme sequences revealed significant enrichment in metagenomes of subjects with colorectal cancer.

biochemistry↗

bioRxiv2021

Diversity and distribution of sulfur metabolism in the human gut microbiome and its association with colorectal cancer

Microbial sulfidogenesis produces genotoxic hydrogen sulfide (H2S) in the human gut using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates, however the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr). Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut. Here we show that microbial sulfur metabolism is more abundant and diverse than previously studied and is statistically associated with CRC. Using ~17,000 bacterial genomes from publicly available stool metagenomes, we studied the diversity of sulfur metabolic genes in 667 participants across different health statuses: healthy, adenoma, and carcinoma. Sulfidogenic genes were harbored by 142 bacterial genera and both organic and inorganic sulfidogenic genes were associated with carcinoma. Significantly, anaerobic sulfite reductases were twice as abundant as dsr. We identified twelve potential pathways for reductive taurine metabolism including novel pathways, and prevalence of organic sulfur metabolic genes indicate these substrates may be the most abundant source of microbially derived H2S. Our findings significantly expand knowledge of microbial sulfur metabolism in the human gut, and highlight key gaps that limit understanding of its potential contributions to the pathogenesis of CRC.

microbiology↗

bioRxiv2019

Microbial community dynamics and coexistence in a sulfide-driven phototrophic bloom

Phototrophic microbial mats commonly contain multiple phototrophic lineages that coexist based on their light, oxygen and nutrient preferences. Here we show that similar coexistence patterns and ecological niches can occur in suspended phototrophic blooms of an organic-rich estuary. The water column showed steep gradients of oxygen, pH, sulfate, sulfide, and salinity. The upper part of the bloom was dominated by aerobic phototrophic Cyanobacteria, the middle and lower parts were dominated by anoxygenic purple sulfur bacteria (Chromatiales) and green sulfur bacteria (Chlorobiales), respectively. We found multiple uncultured phototrophic lineages and present metagenome-assembled genomes of two uncultured organisms within the Chlorobiales. Apparently, those Chlorobiales populations were affected by Microviridae viruses. We suggest a sulfur cycle within the bloom in which elemental sulfur produced by phototrophs is reduced to sulfide by Desulfuromonas sp. These findings improve our understanding of the ecology and ecophysiology of phototrophic blooms and their impact on biogeochemical cycles.

microbiology↗