Biology subjects

Ryan, E. P.

Publications and source records attributed to Ryan, E. P..

3 recordsLinked to original sources

bioRxiv2020

Metabolomics and proteomics of L. rhamnosus GG and E. coli Nissle probiotic supernatants identify distinct pathways that mediate growth suppression of antimicrobial-resistant pathogens

Probiotics merit testing as alternatives to conventional antibiotics and are receiving increased attention for efficacy against multi-drug resistant pathogen infections. This study hypothesis was that the Gram-positive probiotic, L. rhamnosus GG (LGG) and Gram-negative E. coli Nissle (ECN) secrete distinct proteins and metabolites to suppress pathogen growth. LGG and ECN cell free supernatants were tested in a dose-dependent manner for differential growth suppression of Salmonella Typhimurium, Escherichia coli, and Klebsiella oxytoca that harbor antimicrobial resistance (AMR). Across supernatant doses, LGG was 6.27% to 20.55% more effective than ECN at suppressing AMR pathogen growth. Proteomics and metabolomics were performed to identify pathways that distinguished LGG and ECN for antimicrobial functions. From the 667 detected metabolites in probiotic cell free supernatants, 304 metabolites had significantly different relative abundance between LGG and ECN, and only 5 and 6 unique metabolites were identified for LGG and ECN respectively. LGG and ECN differences involved amino acid, energy and nucleotide metabolism. Proteomics analysis of ECN and LGG cell free supernatants identified distinctions in 87 proteins, where many were related to carbohydrate and energy metabolism. Integration of genome-proteome-metabolome signatures from LGG and ECN with predictive metabolic modeling supported differential use of substrates by these two probiotics as drivers of antimicrobial actions. ECN metabolized a range of carbon sources, largely purines, whereas LGG consumed primarily carbohydrates. Understanding functional biosynthesis, utilization and secretion of bioactive metabolites and proteins from genetically distinct probiotics will guide strategic approaches for developing antibiotic alternatives and for controlling spread of multi-drug resistant pathogens. ImportanceProbiotics are practical alternatives for protection against antimicrobial resistant pathogens. Bioactive probiotics molecules merit further investigation using high throughput - omic approaches. This study identified functional differences between Gram-positive L. rhamnosus GG (LGG) and Gram-negative E. coli Nissle (ECN) probiotics that suppressed the growth of antimicrobial resistant S. Typhimurium, K. oxytoca, and E. coli. Proteomes and metabolomes of the probiotic cell free supernatants showed metabolic differences between LGG and ECN for mediating pathogen growth suppression. Metabolites distinguishing LGG versus ECN growth suppression included carbohydrates, lipids, amino acids, and nucleic acids. The metabolic flux differences between ECN and LGG, which coincided with observed separations in the proteomes and metabolomes, was hypothesized to explain the differential suppression of AMR pathogens. Integrated metabolite and protein signatures produced by each probiotic merit attention as adjuvant therapeutics for antimicrobial resistant infections.

microbiology↗

bioRxiv2020

Rice Bran and Quercetin Produce a Positive Synergistic Effect on Human Gut Microbiota, Elevate the Level of Propionate, and Reduce the Population of Enterobacteriaceae family when Determined using a Bioreactor Model.

Diet is one of the prominent determinants of gut microbiota composition significantly impacting human health. Recent studies with dietary supplements such as rice bran and quercetin have been shown to provide a beneficial impact on the host by positively influencing the gut microbiota. However, the specific bacterial species impacted when rice bran or quercetin is present in the diet is not well understood. Therefore, in this study, we used a minibioreactor array system as a model to determine the effect of quercetin and rice bran individually, as well as in combination, on gut microbiota without the confounding host factors. We found that rice bran exerts higher shift in gut microbiome composition when compared to quercetin. At the species level, Acidaminococcus intestini was the only significantly enriched taxa when quercetin was supplemented, while 15 species were enriched in rice bran supplementation and 13 were enriched when quercetin and rice bran were supplemented in combination. When comparing the short chain fatty acid production, quercetin supplementation significantly enriched isobutyrate production while propionate dominated the quercetin and rice bran combined group. Higher levels of propionate were highly correlated to the lower abundance of the potentially pathogenic Enterobacteriaceae family. These findings suggest that the combination of rice bran and quercetin serve to enrich beneficial bacteria and reduce potential opportunistic pathogens. However, further in vivo studies are necessary to determine the synergistic effect of rice bran and quercetin on host health and immunity. ImportanceRice bran and quercetin are dietary components that shape host health by interacting with the gut microbiome. Both these substrates have been reported to provide nutritional and immunological benefits individually. However, considering the complexity of the human diet, it is useful to determine how the combination of food ingredients such as rice bran and quercetin influences the human gut microbiota. Our study provides insights into how these ingredients influence microbiome composition alone and in combination in vitro. This will allow us to identify which species in the gut microbiome are responsible for biotransformation of these dietary ingredients.. Such information is helpful for the development of synbiotics to improve gut health and immunity.

microbiology↗

bioRxiv2019

Rice bran supplementation modulates growth, microbiome and metabolome in weaning infants: a clinical trial in Nicaragua and Mali

Rice bran supplementation provides nutrients, prebiotics and phytochemicals that enhance gut immunity, reduce enteric pathogens in mice and diarrhea in neonatal pigs, and warranted attention for improvement of environmental enteric dysfunction (EED) in children at risk. EED is a condition that drives childhood stunting via intestinal dysbiosis and impaired nutrient metabolism. This study investigated effects of rice bran supplementation on growth, EED biomarkers, gut microbiome and metabolome in weaning infants from 6 to 12 months old in Nicaragua and Mali. Healthy infants were randomized to a control group or rice bran group that received daily supplementation at increasing doses each month. Stool microbiomes were characterized using 16S rDNA amplicon sequencing. Stool metabolomes were analyzed using ultra-high-performance liquid-chromatography tandem mass-spectrometry. Statistical comparisons were completed at 6, 8, and 12 months of age. Daily consumption of rice bran was safe and feasible for infant growth, decreasing alpha-1 antitrypsin levels, and modulating gut microbiome and metabolome when compared to control. Rice bran merits investigation as a practical intervention strategy that could decrease EED prevalence and risk for children from low- and middle-income countries where rice is grown as a staple food, and bran is used as animal feed or wasted. One Sentence SummaryDietary rice bran supplementation during infant weaning from 6-12 months of age improved growth outcomes, modulated environmental enteric dysfunction biomarkers, and supported metabolism by the gut microbiome. The authors declare no competing financial or non financial interests to disclose as defined by Nature Research. There are also no other interests that might be perceived to influence the results and/or discussion reported in this paper. Correspondence and requests for materials should be addressed to Dr. Elizabeth Ryan (e.p.ryan@colostate.edu).

clinical trials↗