The gut microbiota-neuroimmune crosstalk and neuropathic pain: a scoping review.

Environmental stressors can disrupt the gut-brain relationship and alter the gut microbial composition, potentially leading to chronic pain, including neuropathic pain (NP). To understand this complex relationship, we conducted a systematic scoping review to examine the gut microbial-neuroimmune connection to NP and the potential therapeutic targets. The review includes English-language manuscripts in databases such as MEDLINE, Cochrane, and DOAJ between January 2000 and April 2022. Out of the 48 full texts examined, only 15 articles met the inclusion criteria. These included a randomised controlled trial involving 327 individuals, an in vitro, and 13 animal model studies. The findings suggest that the gut flora plays a role in the immunological, neurological, and metabolic signalling pathways associated with NP. Animal studies have been the primary focus in this area, indicating that an imbalanced-gut microbiome and subsequent activation of biochemical and neuro-immunologic pathways may influence the development of NP. This review provides a comprehensive summary of the gut microbiome-immune-NP axis and identifies potential therapeutic targets. However, since most of the evidence comes from animal studies, future research should include clinical trials to gain a better understanding of the role of gut microbiota in NP and discover new therapeutic strategies.

Evidence for higher red blood cell mass in persons with unconjugated hyperbilirubinemia and Gilbert's syndrome.

BACKGROUND: The genetic polymorphism responsible from Gilbert's syndrome is not sufficient for the clinical phenotype to occur in many persons. Additional factors are believed to contribute in pathogenesis. Red cell mass may be such a factor. METHODS: We have retrospectively evaluated computer records of all liver function tests assayed between January 2005 and February 2006. The database was screened to find cases with unconjugated hyperbilirubinemia and normal liver enzymes and blood count values on simultaneous assays. The control group for comparison of surrogate markers of total red cell mass comprised of age- and gender-matched persons who had laboratory tests with completely normal results on the same day with the hyperbilirubinemic cases. Gilbert's syndrome cases were found with medical record assessment, and these cases and their control subjects were more strictly assessed. Three different control groups were established for Gilbert's syndrome cases, one of them including healthy blood donors and personnel. RESULTS: In 48,516 otherwise normal laboratory test results, we have found that 491 male subjects and 323 female subjects with unconjugated hyperbilirubinemia had higher hemoglobin, hematocrit, and red blood cell values compared with age- and gender-matched control subjects (P < 0.001 for all comparisons). Twenty-six males who had been followed for Gilbert's syndrome also showed higher hemoglobin, hematocrit and red cell count values in comparison to all control groups. Mean red cell volume value did not differ between the hyperbilirubinemic persons and control groups. CONCLUSIONS: Relatively increased red cell mass probably plays a role in the pathogenesis of Gilbert's syndrome.