"Feed a Cold, Starve a Fever?" A Review of Nutritional Strategies in the Setting of Bacterial Versus Viral Infections.

PURPOSE OF REVIEW: Some data, mostly originally derived from animal studies, suggest that low glucose intake is protective in bacterial sepsis but detrimental in overwhelming viral infections. This has been interpreted into a broad belief that different forms of sepsis may potentially require different nutritional management strategies. There are a few mechanistic differences between the host interactions with virus and bacteria which can explain why there may be opposing responses to macronutrient and micronutrient during the infected state. Here, we aim to review relevant evidence on the mechanisms and pathophysiology of nutritional management strategies in various infectious syndromes and summarize their clinical implications. RECENT FINDINGS: Newer literature - in the context of the SARS-CoV-19 pandemic - offers some insight to viral infections. There is still limited clinically applicable data during infection that clearly delineate the role of nutrition during an active viral vs bacterial infections. Based on contrasting findings in different models of viruses and bacteria, the macronutrient and micronutrient needs may depend more on specific infectious organisms that may not be generalizable as bacterial versus viral. Overall, the metabolic effects of sepsis are context dependent, and various host-specific (e.g., age, baseline nutritional status, immune status, comorbidities) and illness variables (phase, duration, and severity of illness) play a significant role in determining the outcome besides pathogen-specific (virus or bacterial or fungi and combined infections) factors. Microbe therapy (probiotics and prebiotics) seems to have therapeutic potential in both viral and bacterial infected states, and this seems like a promising area for further practical research.

A STING agonist preconditions against ischaemic stroke via an adaptive antiviral Type 1 interferon response.

Converging lines of inquiry have highlighted the importance of the Type I antiviral response not only in defending against viruses but also in preconditioning the brain against ischaemic stroke. Despite this understanding, treatments that foster brain resilience by driving antiviral interferon responses have yet to be developed for human use. Studies from our laboratory showed that tilorone, the first human antiviral immunomodulatory agent to be developed, robustly preconditioned against stroke in mice and rats. Tilorone is a DNA intercalator; therefore, we hypothesized that it stabilizes cytosolic DNA (released from the mitochondria or the nucleus), thereby activating cyclic GMP-AMP synthase, a homeostatic DNA sensor, and its downstream pathway. This pathway involves st imulator of in terferon g enes (STING), tank-binding kinase 1 (TBK1), and i nterferon r egulatory p rotein-3 and culminates in a protective Type I interferon response. We tested this hypothesis by examining the ability of structurally diverse small-molecule agonists of STING to protect against oxygen/glucose deprivation in vitro in mouse cortical cultures and in vivo against transient ischaemia in mice. The STING agonists significantly reduced cell death both in vitro and in vivo but failed to do so in STING knockout mice. As expected, STING agonist-induced protection was associated with the induction of interferon related genes and the effects could be abrogated in vitro by a TBK1 inhibitor. Taken together, these findings in mice identify STING as a therapeutic target for preconditioning the brain against ischaemic stroke in vitro and in vivo. Moreover, they suggest that clinically approved STING agonists such as Ganciclovir or α-Mangostin are candidate drugs that could be tested in humans as a prophylactic treatment to alleviate brain injury associated with ischaemic stroke.