Search bioRxiv⌕ Search

Biology subjects

Kraft, C. S.

Publications and source records attributed to Kraft, C. S..

3 recordsLinked to original sources

Diet-Microbiome Analysis in a Healthy Cohort Reveals Potential Role of Intestinal Microbiota in Metabolism

Both preclinical and clinical studies have revealed the indisputable importance of intestinal bacterial community composition in pathogenesis of various disease states, from obesity to neurodegeneration. Diet remains one of the most important factors shaping human intestinal microbiota composition. In this study, we investigated diet-microbiome interactions in a healthy cohort of 88 participants from Atlanta and Calgary. We examine microbial composition (16S rRNA sequencing) with dietary records using Spearman Correlation tests with Benjamini-Hochberg multiple hypothesis correction to make community-level comparisons between dietary scores and microbial diversity index scores. Predictive models were used for molecular-level comparisons between microbial gene pathways and molecules. Among generalized dietary and microbial indices, we identified a negative association between dietary whole grain consumption and a microbial dysbiosis score. Comparisons between dietary food groups and bacterial family abundance reveal significant associations between dairy consumption and Lactobacillaceae abundance, dietary unsaturated to saturated fatty acid ratio and Clostridia Cluster Family XIII, salt intake and Lachnospiraceae, and consumption of greens and beans and Veillonellaceae. Predictive models of microbial gene pathways and molecules reveal significant positive associations between several dietary fatty acids and microbial short-chain fatty acid fermentation pathways, and between dietary lignans and archaeal methanogenesis pathways. Overall, these associations may inform future explorations on specific dietary interventions to impact the gut microbiome. IMPORTANCEIn this study, we compare dietary records and composition of intestinal microbes in a cohort of 88 participants. We identified associations between dietary consumption of dairy and the presence of dairy-consuming bacteria called Lactobacteriaceae and between consumption of dietary fats and the presence of fat-consuming bacteria called Clostridia. Using predictive analysis, we identify specific fatty acids associated with specific biochemical pathways found in Clostridia that might underlie these associations, in addition to an association between archaeal microbes and dietary consumption of estrogen-binding molecules called lignans, which are commonly found in whole grains and vegetables. Overall, our study generates useful associations between diet and intestinal microbes that can be tested in experiments that may help scientists use diet to control intestinal microbes in order to improve human health.

microbiology↗

Test Agreement Between Roche Cobas 6800 and Cepheid GeneXpert Xpress SARS-CoV-2 Assays at High Cycle Threshold Ranges

The SARS-CoV-2 pandemic has changed the face of the globe and upended the daily lives of billions. In an effort to bring mass-testing to as many as possible, multiple diagnostic tests including molecular, antigen detection and serological assays have been rapidly developed. However, there is very little information on positive test agreement across modalities, especially for lower viral loads. Thirty-five nasopharyngeal samples that had cycle threshold (Ct) values greater than 30.0 from the Roche cobas 6800 assay were run on the Cepheid GeneXpert Xpress SARS-CoV-2 assay. Ct values ranged from 30.1 to 37.9 (mean 36.7 {+/-} 1.9) on the Roche cobas 6800 assay and 24.6 to 42.4 (mean 32.8{+/-}4.1) on the Cepheid assay. There was a bias of 0.33 {+/-} 3.21, (mean difference -1.59, 95% limits of agreement -5.97, 6.63) signifying close agreement between the 2 instruments with a high standard deviation. The close test agreement between the cobas 6800 and GeneXpert at high Ct values allows for utilization of both assays interchangeable in accordance with testing algorithms.

microbiology↗

Novel Immunoassay for Diagnosis of Ongoing Clostridioides difficile Infections Using Serum and Medium Enriched for Newly Synthesized Antibodies (MENSA)

BACKGROUNDClostridioides difficile infections (CDI) have been a challenging and increasing serious concern in recent years. While early and accurate diagnosis is crucial, available assays have frustrating limitations OBJECTIVEDevelop a simple, blood-based immunoassay to accurately diagnose patients suffering from active CDI. MATERIALS AND METHODSUninfected controls (n=95) and CDI patients (n=167) were recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinant C. difficile antigens. RESULTSSixty-six percent of CDI patients produced measurable responses to C. difficile antigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in MENSA, and 27/167 (16%) were detectable only in serum. DISCUSSIONWe describe the results of a multiplex immunoassay for the diagnosis of ongoing CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, serum-positive only, MENSA- and serum-positive, and MENSA- and serum-negative. The MENSA positive-only patients accounted for 30% and may be attributed to nascent antibody secretion in MENSA prior to seroconversion. Conversely, the serum positive-only subset may have been more advanced in their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI patients who were not identified using MENSA or serum immunoassays. IMPORTANCEWhile there was considerable overlap between patients identified through MENSA and serum, both methods detected additional, unique patients. The combined use of both MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host humoral immune responses in CDI patients.

microbiology↗