Western-style diet (WSD), which is high in fat and low in fiber, lacks nutrients to support gut microbiota. Consequently, WSD reduces microbiota density and promotes microbiota encroachment, potentially influencing colonization resistance, immune system readiness, and thus host defense against pathogenic bacteria. Here we examined the impact of WSD on infection and colitis in response to Citrobacter rodentium. We observed that, relative to mice consuming standard rodent grain-based chow (GBC), feeding WSD starkly altered the dynamics of Citrobacter infection, reducing initial colonization and inflammation but frequently resulting in persistent infection that associated with low-grade inflammation and insulin resistance. WSD’s reduction in initial Citrobacter virulence appeared to reflect that colons of GBC-fed mice contain microbiota metabolites, including short-chain fatty acids, especially acetate, that drive Citrobacter growth and virulence. Citrobacter persistence in WSD-fed mice reflected inability of resident microbiota to out-compete it from the gut lumen, likely reflecting the profound impacts of WSD on microbiota composition. These studies demonstrate potential of altering microbiota and their metabolites by diet to impact the course and consequence of infection following exposure to a gut pathogen.

Vascular aging, characterized by arterial thickening, reduced elasticity, and endothelial dysfunction, significantly compromises vascular health and accelerates the progression of cardiovascular diseases (CVDs). Emerging research highlights the gut–vascular axis as a critical mediator of vascular health, with the gut microbiota (GM) playing a pivotal role in modulating vascular aging and CVDs. This review presents a thorough and up-to-date discussion of the fundamental mechanisms driving vascular aging and explores how GM and its metabolites influence these processes. Furthermore, we place particular emphasis on therapeutic strategies, including probiotics and food-derived natural products, that foster beneficial bacterial growth and support cardiovascular health, while also exploring the underlying mechanisms. By targeting GM composition and function, these approaches offer promising strategies to mitigate vascular aging and lower CVD risk. Future studies aimed at deepening our understanding of the interplay between GM, its metabolites, and vascular health could pave the way for novel preventive and therapeutic interventions against vascular aging and CVDs.

Different types of dietary fibers exert distinct effects on gut microbiota and overall health, playing a complex role in disease-specific contexts. Here, we found that while supplementation with dietary soluble fiber inulin does not induce inflammation under steady-state conditions, it exacerbates intestinal inflammation in a DSS-induced colitis mouse model in a gut microbiota-dependent manner. Mechanistically, we found that inulin consumption increases the overall bacterial load with expansion of pro-colitis pathobiont, elevates levels of pro-inflammatory component flagellin, and reduces microbial diversity. These microbiota changes drove colitis aggravation via GR-1⁺ cell-mediated inflammation. Using NLRC4/TLR5- and MyD88-deficient mice, we identified microbiota-derived pro-inflammatory signals-particularly flagellin-as key mediators of this effect. Moreover, the exacerbation of colitis was abolished in IL-18 knockout mice, indicating a critical role for inflammasome signaling in mediating this response. Notably, maternal consumption of an inulin-enriched diet during lactation altered the offspring's gut microbiota and increased their susceptibility to DSS-induced colitis. Collectively, our findings suggest that inulin intake exacerbates DSS induced colitis through microbiota-mediated inflammation and MyD88/IL-18 signaling, with the effects persist in the offspring. These results underscore the importance of considering fiber type in disease-specific dietary interventions, supporting the idea that a more balanced intake of natural dietary fibers that foster a diverse and resilient gut microbiota may offer greater benefits for intestinal health.

We quantitated anti-SARS/CoV-2 IgG and IgM by ELISA in self-collected blood samples (n=142) in arbitrarily-selected metro Atlanta residents, primarily acquaintances of the authors’ lab members from 4/17-4/27, 2020. Archived serum (n=34), serum from nucleic acid test (NAT)-positive subjects (n=4), and samples collected from NAT-positive community members (n=4) served to validate the assay. The range of anti-SARS/CoV-2 antibodies in archived and NAT-positive sera indicated need to compromise sensitivity or specificity. Accordingly, we set a cutoff of 4 SD above the mean for IgG and 3 SD above the mean for IgM to indicate that an individual had been exposed, and developed some degree of immunity, to SARS/CoV-2. The IgG cutoff clearly compromised sensitivity but offered high specificity, both of which were harder to gauge for IgM. Based on these cutoffs, excluding subjects whose participation resulted from self-suspected SARS/CoV-2 infection, we found 7.1% positivity for anti-SARS/CoV-2 IgG (3 of 127 subjects) or IgM (6 of 127). While we do not claim this small immune survey is broadly representative of metro Atlanta, and we have greater confidence in the IgG results, which had only 2.4% positivity, it nonetheless demonstrates that persons with antibodies to SARS/CoV-2, who’ve not suspected they’d been exposed to this virus, can readily be found in various Atlanta area neighborhoods (9 positives were in 8 zip codes). Accordingly, these results support the notion that dissemination of the virus is more widespread than testing would indicate but also suggests that most persons in metro Atlanta remain vulnerable to this virus. More generally, these results support the general utility of sero-surveillance to guide public policy but also highlight the difficulty of discerning if individuals have immunity to SARS/CoV-2.

Summary: Administration of bacterial flagellin elicits production of TLR5-mediated IL-22 and NLRC4-mediated IL-18 that act in concert to cure and prevent rotavirus (RV) infection. This study investigated the mechanism by which these cytokines act to impede this virus. Although IL-18 and IL-22 induce each other’s expression, we found that IL-18 and IL-22 both impeded RV independently of each other and did so by distinct mechanisms, in both cases via activation of their cognate receptors in intestinal epithelial cells (IEC). IL-22 drove IEC proliferation and migration toward villus tips, which resulted in increased extrusion of highly differentiated IEC that serve as the site of RV replication. In contrast, IL-18 induced pyroptotic death of RV-infected IEC thus directly interrupting the RV replication cycle, resulting in spewing of incompetent virus into the intestinal lumen and causing a rapid drop in levels of RV-infected IEC. Together, these actions resulted in rapid and complete expulsion of RV, even in hosts with severely compromised immune systems. These results suggest that IL-18/22 might be a means of treating viral infections that preferentially target short-lived epithelial cells.