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Background: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. β‐Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti‐inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms. Methods: An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS‐induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH‐DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents. Results: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF‐α, IL‐1β, and IL‐6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti‐inflammatory cytokines (IL‐10), while also inhibiting HS‐induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF‐α and IL‐1β) in mouse BV2 cells. Conclusion: β‐Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut–brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota. [ABSTRACT FROM AUTHOR]

Respiratory diseases are responsible for a greater mortality rate around the world. Viral or bacterial infections in the respiratory tract have been identified as major causative agents for death and disability among the population. Respiratory tract infections (RTIs) cause severe respiratory ailments starting from coldlike symptoms, eventually affecting the lungs and other viscera, and are mainly categorized into two types depending on the affected area: upper RTIs and lower RTIs. Respiratory viruses belong to several viral families such as influenza virus, enterovirus, adenovirus, respiratory syncytial virus, and recently severe acute respiratory syndrome coronavirus 2. Studies have indicated that people with good immune functions are less prone to respiratory infections and also their recovery rate is quicker. Innate and acquired immune systems actively participate in the recognition and elimination of the pathogenic agents. In the present context, the potential of probiotics is recognized as viable microorganisms that support the balance of the beneficial microbial population in the gastrointestinal tract and promote host immunity. The probiotics have long been known to regulate bodily immune functions and have been used against general RTIs such as cough, pharyngitis, laryngitis, pneumonia, and asthma. In addition, intervention with probiotics could directly affect the composition of the gut microbiota that have been shown to palliate respiratory diseases by modulating pulmonary immune activities through the gut–lung axis, and therefore, probiotics could become an alternative therapeutic approach for RTIs. [ABSTRACT FROM AUTHOR]

The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the nonpsychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota–gut–brain axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control. Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation. Thus, cannabinoids may exert AUD harm‐reduction effects, at least in part, through their beneficial actions across the MGBA. This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions. [ABSTRACT FROM AUTHOR]