The gut–brain axis (GBA) plays a pivotal role in human health and wellness by orchestrating complex bidirectional regulation and influencing numerous critical processes within the body. Over the past decade, research has increasingly focused on the GBA in the context of inflammatory bowel disease (IBD). Beyond its well-documented effects on the GBA–enteric nervous system and vagus nerve dysregulation, and gut microbiota misbalance—IBD also leads to impairments in the metabolic and cellular functions: metabolic dysregulation, mitochondrial dysfunction, cationic transport, and cytoskeleton dysregulation. These systemic effects are currently underexplored in relation to the GBA; however, they are crucial for the nervous system cells’ functioning. This review summarizes the studies on the particular mechanisms of metabolic dysregulation, mitochondrial dysfunction, cationic transport, and cytoskeleton impairments in IBD. Understanding the involvement of these processes in the GBA may help find new therapeutic targets and develop systemic approaches to improve the quality of life in IBD patients.

The present study is aimed to elucidate the possible involvement of the thermosensitive TRPM2 ion channel in changing of the temperature sensitivity of the hypothalamus after different cold exposures—long-term adaptation to cold and short-term cooling. Quantitative RT-PCR was used to study the expression of the gene of thermosensitive TRPM2 ion channel in the hypothalamus in the groups of control (kept for 5 weeks at +20 to +22 °C) and cold-adapted (5 weeks at +4 to +6 °C) rats, as well as in the groups of animals which were subjected to acute cooling (rapid or slow) with subsequent restoration of body temperature to the initial level. It has been shown that after long-term adaptation to cold, the decrease in the Trpm2 gene expression was observed in the hypothalamus, while a short-term cooling does not affect the expression of the gene of this ion channel. Thus, long-term adaptation to cold results in the decrease in the activity not only of the TRPV3 ion channel gene, as shown earlier, but also of the Trpm2 gene in the hypothalamus. The overlapping temperature ranges of the functioning of these ion channels and their unidirectional changes during the adaptation of the homoeothermic organism to cold suggest their functional interaction. The decrease in the Trpm2 gene expression may indicate the participation of this ion channel in adaptive changes in hypothalamic thermosensitivity, but only as a result of long-term cold exposure and not of a short-term cooling. These processes occurring at the genomic level are one of the molecular mechanisms of the adaptive changes.