Alzheimer's disease (AD) is a neurodegenerative disease that impacts 45 million people worldwide and is ranked as the 6th top cause of death among all adults by the Centers for Disease Control and Prevention. While genetics is an important risk factor for the development of AD, environment and lifestyle are also contributing risk factors. One such environmental factor is diet, which has emerged as a key influencer of AD development/progression as well as cognition. Diets containing large quantities of saturated/trans-fats, refined carbohydrates, limited intake of fiber, and alcohol are associated with cognitive dysfunction while conversely diets low in saturated/trans-fats (i.e., bad fats), high mono/polyunsaturated fats (i.e., good fats), high in fiber and polyphenols are associated with better cognitive function and memory in both humans and animal models. Mechanistically, this could be the direct consequence of dietary components (lipids, vitamins, polyphenols) on the brain, but other mechanisms are also likely to be important. Diet is considered to be the single greatest factor influencing the intestinal microbiome. Diet robustly influences the types and function of micro-organisms (called microbiota) that reside in the gastrointestinal tract. Availability of different types of nutrients (from the diet) will favor or disfavor the abundance and function of certain groups of microbiota. Microbiota are highly metabolically active and produce many metabolites and other factors that can affect the brain including cognition and the development and clinical progression of AD. This review summarizes data to support a model in which microbiota metabolites influence brain function and AD.

Tryptamine is a naturally occurring monoamine alkaloid which has been shown to act as an aryl hydrocarbon receptor (AHR) agonist. It is produced in large quantities from the catabolism of the essential amino acid tryptophan by commensal microorganisms within the gastrointestinal (GI) tract of homeothermic organisms. Previous studies have established microbiota derived AHR ligands as potent regulators of neuroinflammation, further defining the role the gut-brain axis plays in the complex etiology in multiple sclerosis (MS) progression. In the current study, we tested the ability of tryptamine to ameliorate symptoms of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We found that tryptamine administration attenuated clinical signs of paralysis in EAE mice, decreased the number of infiltrating CD4⁺ T cells in the CNS, Th17 cells, and RORγ T cells while increasing FoxP3+Tregs. To test if tryptamine acts through AHR, myelin oligodendrocyte glycoprotein (MOG)-sensitized T cells from wild-type or Lck-Cre AHR^flox/flox mice that lacked AHR expression in T cells, and cultured with tryptamine, were transferred into wild-type mice to induce passive EAE. It was noted that in these experiments, while cells from wild-type mice treated with tryptamine caused marked decrease in paralysis and attenuated neuroinflammation in passive EAE, similar cells from Lck-Cre AHR^flox/flox mice treated with tryptamine, induced significant paralysis symptoms and heightened neuroinflammation. Tryptamine treatment also caused alterations in the gut microbiota and promoted butyrate production. Together, the current study demonstrates for the first time that tryptamine administration attenuates EAE by activating AHR and suppressing neuroinflammation.

Background: As an important autoimmune disease, type 1 diabetes (T1D) is often diagnosed in children, but due to the complexity of the etiology of diabetes and many other factors, the disease pathogenesis of diabetes is still unclear. The intestinal microbiota has been proved to have close relationships with T1D in recent years, which is one of the most important molecular bases of pathogenesis and prognosis factors for T1D. Using the multi-omics and multicenter sample analysis method, a number of intestinal microbiota in T1D have been discovered and explained, which has provided comprehensive and rich information. However, how to find more useful information and get an intuitive understanding that people need conveniently in the huge data sea has become the focus of attention. Therefore, quantitative analysis and visualization of the interaction between intestinal microbiota and T1D in children are urgently needed. Methods: We retrieved the detailed original data from the National Center for Biotechnology Information, GMREPO, and gutMEGA databases and other authoritative multiple projects with related research; the ranking of intestinal microbiota abundance from healthy people, overall T1D patients, and T1D in children (0-18 years old) were detailed analyzed, classified, and visualized. Results: A total of 515 bacterial species and 161 related genera were fully analyzed. Also, Prevotella copri was led by 21.25% average abundance, followed by Clostridium tertium of 10.39% in all-cross T1D patients. For children with T1D, Bacteroides vulgatus has high abundance in all age periods, whereas the abundance of each intestinal microbiota was more uniform in female samples, with the ranking from high to low as Bacteroides dorei 9.56%, P. copri 9.53%, Streptococcus pasteurianus 8.15%, and C. tertium 7.53%, whereas in male samples, P. copri was accounted for the largest by 22.72%. The interaction between intestinal microbiota and comparison between healthy people and children with T1D was also detailed analyzed. Conclusions: This study provides a new method and comprehensive perspectives for the evaluation of the interaction between intestinal microbiota and T1D in children. A set of useful information of intestinal microbiota with its internal interaction and connections has been presented, which could be a compact, immediate, and practical scientific reference for further molecular biological and clinical translational research of T1D in children.

The aim of this paper was to summarise knowledge of IL-22 involvement in multiple sclerosis (MS) and the possible link between IL-22 and two transcription factors - AHR and c-Maf. The conclusion is that despite numerous studies, the exact role of IL-22 in the pathogenesis of MS is still unknown. The expression and function of c-Maf in MS have not been studied. It seems that the functions of c-Maf and AHR are at least partly connected with IL-22, as both directly or indirectly influence the regulation of IL-22 expression. This possible connection has never been studied in MS.