Biology subjects

Griffin, L. E.

Publications and source records attributed to Griffin, L. E..

3 recordsLinked to original sources

bioRxiv2025

Gram-positive bacterial cell wall components inhibit herpes simplex virus infection.

The role of the mucosal microbiome in viral infections remains unclear. Genital herpes, caused by herpes simplex virus 1 and 2 (HSV-1 and HSV-2), is among the most prevalent sexually transmitted infections worldwide. Despite evidence linking vaginal Lactobacillus to protection against sexually transmitted viruses, the specific microbial components and mechanisms that mediate this defense are not well understood. Here, we show that multiple cell wall components from diverse gram-positive bacteria, including lactobacilli, inhibit HSV-1 and HSV-2 infection in cells and in a mouse model of genital herpes infection. Peptidoglycan (PG) and lipoteichoic acid (LTA), both major components of the gram-positive bacterial cell wall, significantly reduced HSV infectivity in vitro and improved survival and disease outcomes in mice. We further showed that Lactobacillus crispatus surface layer proteins SlpA and SlpB bind HSV-1 and inhibit infection. Antiviral effects of cell wall components were dose-dependent, relied on intact PG structure, and, in the case of PG and LTA, were independent of TLR2-mediated host signaling. Collectively, our findings identify a species-independent antiviral function for gram-positive bacterial cell wall components against HSV and suggest that the composition of the mucosal microbiome may play an underappreciated role in suppressing mucosal herpes infection in humans.

microbiology↗

bioRxiv2022

Addition of soluble fiber in low fat purified diets improves gut and metabolic health compared to traditional AIN diets

BackgroundPurified diets (PDs) contain refined ingredients with one main nutrient, allowing for greater control relative to grain-based diets (GBDs), which contain unrefined grains and animal byproducts. Traditional PDs like the AIN-76A (76A) and AIN-93G (93G) can negatively impact metabolic and gut health when fed long-term, in part due to lower total fiber, no soluble fiber, and higher sucrose content. ObjectiveTwo studies were conducted to determine how PDs with reduced sucrose and increased fiber (soluble and insoluble) influence metabolic and gut health in mice compared to traditional AIN PDs or GBDs. MethodsIn study 1, C57Bl/6N mice consumed a GBD (5002), 76A, 93G, or 2 Open standard PDs (OSDs) with reduced sucrose and higher fiber for 88 days. Body composition and metabolic parameters were assessed. In study 2, C57Bl/6N mice consumed either 2 GBDs (5001 or 5002) or OSDs with different types/levels of fiber for 14 days. Microbiome alterations and predicted functional metagenomic changes were measured. ResultsOSD marginally influenced body weight and adiposity, but improved glucose tolerance relative to 93G (p = 0.0131) and 76A (p = 0.0014). Cecal and colonic weights were lower in mice fed cellulose-based PDs compared to those fed GBDs and soluble fiber PDs. Soluble fiber diets reduced alpha diversity and showed similar beta diversity, which differed from cellulose fed PDs and GBDs. Certain genera associated with improved gut health such as Bifidobacteria and Akkermansia were significantly elevated by soluble fibers PDs (p[≤]0.01). Some metabolic pathways related to carbohydrate and fatty acid metabolism were affected by PDs. ConclusionPDs formulated with lower sucrose and increased fiber content, particularly soluble fiber, blunted elevations in metabolic parameters and favorably impacted microbiota and metagenome in C57BL/6N mice.

physiology↗

bioRxiv2020

Microbial metabolites of flavanols in urine are associated with enhanced anti-proliferative activity in bladder cancer cells in vitro

Dietary flavanols and their metabolites are excreted primarily via the urine, suggesting uroepithelial cells as a site of activity due to lengthy exposure to high concentrations of these compounds. Flavanols are metabolized by the gut microbiota to numerous bioavailable metabolites. The observed effects of flavanols, including cancer chemoprevention, may be due in part to the activities of microbial metabolites. Most in vitro mechanistic work in this area relies on a limited pool of commercially available or synthesized flavanol microbial metabolites, and little work has been done in the area of bladder cancer. The impact of physiologically relevant mixtures of native flavanols and their metabolites generated in vivo remains unknown. Rats were fed various flavanols after which 48 h urine samples, approximating the total bioavailable metabolome, were collected. Urine samples were profiled by UPLC-MS/MS, and their anti-proliferative activities were assayed in vitro in four bladder cancer cell models. Significant interindividual variability was observed for chemical profiles and anti-proliferative activities. Concentrations of microbial metabolites (valerolactones, phenylalkyl acids and hippuric acids) were positively associated with reduced bladder cancer cell proliferation in vitro, while native flavanols were poorly correlated with activity. These results suggest that microbial metabolites may be the primary compounds responsible for chemoprevention in uroepithelial cell following flavanol consumption. Furthermore, this highlights the potential for exploiting knowledge about individual genetics, microbiome profiles, flavonoid metabolism profiles, tumor characteristics, etc. to design personalized dietary interventions for cancer prevention and/or adjuvant therapy to reduce bladder cancer incidence and improve outcomes.

cancer biology↗