Biology subjects

Theriot, C. M.

Publications and source records attributed to Theriot, C. M..

22 records · Page 2Linked to original sources

bioRxiv2019

Characterization of C. difficile strains isolated from companion animals and the associated changes in the host fecal microbiota

BackgroundClostridioides difficile is an enteric pathogen historically known to cause hospital associated (HA)-infections in humans. A major risk factor for CDI in humans is antibiotic usage as it alters the gut microbiota and there is a loss of colonization resistance against C. difficile. In recent years there has been an increase in community associated (CA)-C. difficile infection that does not have the same risk factors as HA-CDI. Potential sources of CA-CDI have been proposed and include animals, food, water, and the environment, however these sources remain poorly investigated. Here, we define the prevalence of C. difficile strains found in different companion animals (canines, felines, and equines) to investigate a potential zoonotic link. C. difficile strains were identified by toxin gene profiling, fluorescent PCR ribotyping, and antimicrobial susceptibility testing. 16s rRNA gene sequencing was done on animal feces to investigate the relationship between the presence of C. difficile and the gut microbiota in different hosts.\n\nResultsHere, we show that C. difficile was recovered from 20.9% of samples (42/201), which included 33 canines, 2 felines, and 7 equines. Over 69% (29/42) of the isolates were toxigenic and belonged to 14 different ribotypes, with overlap between HA- and CA-CDI cases in humans. The presence of C. difficile results in a shift in the fecal microbial community structure in both canines and equines. Commensal Clostridia C. hiranonis was negatively associated with C. difficile in canines. Further experimentation showed a clear antagonistic relationship between the two strains in vitro, suggesting that commensal Clostridia might play a role in colonization resistance against C. difficile in different hosts.\n\nConclusionsIn this study we investigated a potentially important source of C. difficile transmission: the companion animal population. C. difficile carriage was common in dogs, cats, and horses. C. difficile isolates from companion animals included many of the same ribotypes known to cause HA- and CA-CDI in humans, and had similar antimicrobial resistance profiles as those isolated from human populations. These data contribute to our understanding of non-hospital exposure to C. difficile in the human population and suggest new avenues for reducing C. difficile prevalence in companion animals and, perhaps, thereby reducing CA-CDI in humans.

microbiology↗

bioRxiv2019

Secondary bile acid ursodeoxycholic acid (UDCA) alters weight, the gut microbiota, and the bile acid pool in conventional mice

Ursodeoxycholic acid (commercially available as Ursodiol) is a naturally occurring bile acid that is used to treat a variety of hepatic and gastrointestinal diseases. Ursodiol can modulate bile acid pools, which have the potential to alter the gut microbiota community structure. In turn, the gut microbial community can modulate bile acid pools, thus highlighting the interconnectedness of the gut microbiota-bile acid-host axis. Despite these interactions, it remains unclear if and how exogenously administered ursodiol shapes the gut microbial community structure and bile acid pool. This study aims to characterize how ursodiol alters the gastrointestinal ecosystem in conventional mice. C57BL/6J wildtype mice were given one of three doses of ursodiol (50, 150, or 450 mg/kg/day) by oral gavage for 21 days. Alterations in the gut microbiota and bile acids were examined including stool, ileal, and cecal content. Bile acids were also measured in serum. Significant weight loss was seen in mice treated with the low and high dose of ursodiol. Alterations in the microbial community structure and bile acid pool were seen in ileal and cecal content compared to pretreatment, and longitudinally in feces following the 21-day ursodiol treatment. In both ileal and cecal content, members of the Lachnospiraceae family significantly contributed to the changes observed. This study is the first to provide a comprehensive view of how exogenously administered ursodiol shapes the gastrointestinal ecosystem. Further studies to investigate how these changes in turn modify the host physiologic response are important.\n\nImportanceUrsodeoxycholic acid (commercially available as ursodiol) is used to treat a variety of hepatic and gastrointestinal diseases. Despite its widespread use, how ursodiol impacts the gut microbial community structure and bile acid pool remains unknown. This study is the first to provide a comprehensive view of how exogenously administered ursodiol shapes the gastrointestinal ecosystem. Ursodiol administration in conventional mice resulted in significant alterations in the gut microbial community structure and bile acid pool, indicating that ursodiol has direct impacts on the gut microbiota-bile acid-host axis which should be considered when this medication is administered.\n\nBile Acid AbbreviationsMCA - -Muricholic acid; {beta}MCA -{beta}-Muricholic acid; {omega}MCA -{omega}-Muricholic acid; CA - Cholic acid; CDCA - Chenodeoxycholic acid; DCA - Deoxycholic acid; GCDCA - Glycochenodeoxycholic acid; GDCA - Glycodeoxycholic acid; GLCA - Glycolithocholic acid; GUDCA - Glycoursodeoxycholic acid; HCA - Hyodeoxycholic acid; iDCA - Isodeoxycholic acid; iLCA - Isolithocholic acid; LCA - Lithocholic acid; TCA - Taurocholic acid; TCDCA - Taurochenodeoxycholic acid; TDCA - Taurodeoxycholic acid; THCA - Taurohyodeoxycholic acid; TUDCA - Tauroursodeoxycholic acid; T{beta}MCA - Tauro-{beta}-muricholic acid; T{omega}MCA -Tauro {omega}-muricholic acid; UDCA - Ursodeoxycholic acid.

microbiology↗

bioRxiv2018

High-throughput amplicon sequencing of the full-length 16S rRNA gene with single-nucleotide resolution

Targeted PCR amplification and high-throughput sequencing (amplicon sequencing) of 16S rRNA gene fragments is widely used to profile microbial communities. New long-read sequencing technologies can sequence the entire 16S rRNA gene, but higher error rates have limited their attractiveness when accuracy is important. Here we present a high-throughput amplicon sequencing methodology based on PacBio circular consensus sequencing and the DADA2 sample inference method that measures the full-length 16S rRNA gene with single-nucleotide resolution and a near-zero error rate.\n\nIn two artificial communities of known composition, our method recovered the full complement of full-length 16S sequence variants from expected community members without residual errors. The measured abundances of intra-genomic sequence variants were in the integral ratios expected from the genuine allelic variants within a genome. The full-length 16S gene sequences recovered by our approach allowed E. coli strains to be correctly classified to the O157:H7 and K12 sub-species clades. In human fecal samples, our method showed strong technical replication and was able to recover the full complement of 16S rRNA alleles in several E. coli strains.\n\nThere are likely many applications beyond microbial profiling for which high-throughput amplicon sequencing of complete genes with single-nucleotide resolution will be of use.

microbiology↗

bioRxiv2017

Inter-individual Recovery Of The Microbiota And Metabolome Over Time Following Fecal Microbiota Transplantation In Patients With Recurrent Clostridium difficile Infection

A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery, a critical component of disease recovery. However, identification of the specific microbes and their functions that directly impact recovery from CDI remains difficult. We assessed for associations among microbial community members and metabolites in patients with recurrent CDI following treatment with FMT over time to identify groups of bacteria with potential restorative functions. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Increased levels of the secondary bile acid deoxycholic acid and the short chain fatty acids (SCFAs) butyrate, acetate, and propionate were observed post-FMT. To take into account longitudinal sampling and intra-individual differences, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Microbial metabolites that were increased following FMT associated with members classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.\n\nIMPORTANCEClostridium difficile infection (CDI) is an urgent and serious healthcare-associated problem. In recent years, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent CDI, a frequent outcome of disease. While it is apparent that FMT promotes recovery of the microbiota, it is unclear how microbes and their functions promote recovery from disease. This study aimed to identify associations among microbes and metabolites following FMT and to identify critical microbial functions following FMT treatment for recurrent CDI. Overall, recovery of the metabolome was highly dynamic and individualized in all patients, who were all successfully treated. Our results suggest that microbial changes following FMT may be highly specific to the donor-recipient relationship. Further understanding of the host-microbe environments necessary to enable successful transplantation of microbes during FMT could aid development of specific microbial therapeutics for recurrent CDI and other gastrointestinal diseases.

microbiology↗