Altered Host Gut-Resistome and Gut-Immune Axes are linked to Non-cholera Vibrio infection severity in aging and climate change-induced heat stress.

The steady rise of global temperatures due to climate change is an emerging cause of concern and has been long perceived to cause heat stress, heat shock, and even heat stroke. Episodes of heat waves and heat-related injury-related illnesses are a major concern for public health worldwide. In addition, the increasing temperatures worldwide and concomitant coastal flooding due to rising sea waters allow Vibrio blooms (both cholera and non-cholera Vibrios) across the coasts. Both non-cholera and cholera Vibrios lead to large-scale infections and children and the elderly resulting in high morbidity. The non-cholera Vibrios thrive in summer months and bacterial yields are higher in increased salinity. Heat stress (HS) caused by climate change has been long evident to have adverse effects on human health via altering the immune homeostasis. Similarly, since heat stress and Vibrio infections co-exist in areas affected by global warming, resulting in lengthy summer months across the coastlines of India, large swaths of Europe and North America, it is highly likely that non-cholera Vibrio infections will increase in severity due to the dual-hit phenomenon. We hypothesized that aging and a parallel heat stress (HS) event may potentiate the risk of non-cholera Vibrio infections in the host and exacerbate the pathology. Being the most vulnerable cohort as per epidemiological reports and as stated in the scientific premise, elderly individuals are predicted to be at higher risk. The above rationale was used to study this premise in aging mice. To study the underlying pathological changes in possible co-exposure of HS and subsequent non-cholera Vibrio challenge, an aging mouse model was used. Aged C57BL6/J (24 months old) mice were exposed to HS at 40C for three hours/day for 15 days depicting a periodic heat wave exposure. This was followed by a Vibrio vulnificus challenge 24 hours post-HS exposure. Gut microbiome extracted from fecal pellets were analyzed via Whole Meta-genome Sequencing (WMS) and related platforms with different pipelines were used to study the anti-microbial resistance gene signatures. Systemic markers of inflammation were assessed from the serum samples via sandwich ELISA. Intestinal pathology, gut leaching, and immune response were studied by using standard methods of Immuno-histochemistry and Immuno-fluorescence microscopy. Collectively, the research explores a new dimension to the mechanistic insights of Vibrio infection effects and future concerns that could emerge from periodic heat waves globally.