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Capsaicin ameliorates glycemic levels via gut microbiota-derived 5-aminolevulinic acid in mice.

BACKGROUND: Capsaicin, a natural alkaloid in chili peppers, regulates glycemic levels; however, its mechanisms and therapeutic potential remain unclear. This study aimed to elucidate the role of gut microbiota and their metabolites in mediating capsaicin's glycemic regulatory effects. We conducted experiments in specific pathogen-free (SPF) and germ-free (GF) mice, transient receptor potential vanilloid 1 (TRPV1) receptor ablation studies, and fecal microbiota transplantation (FMT) to demonstrate the involvement of gut microbiota in capsaicin-mediated glycemic control. Metagenomics and metabolomics analyses were employed to identify key microbial strains and metabolic pathways. Keystone strains and metabolites were supplemented in GF mice without capsaicin intervention to validate their effects on glycemic regulation. In vitro co-culture experiments were performed to investigate the mutualistic relationships among keystone strains under capsaicin treatment. RESULTS: Gut microbiota constitute an important component of capsaicin-mediated glycemic regulation, acting in concert with but not solely dependent on TRPV1 signaling. Gut microbiota altered by capsaicin promote the production of 5-aminolevulinic acid (5-ALA), which contributes to heme synthesis and enhances glycemic control. Supplementation with Akkermansia muciniphila, Ligilactobacillus murinus, or 5-ALA in GF mice recapitulates the glycemic benefits of capsaicin. Furthermore, capsaicin enriches Akkermansia muciniphila, which in turn supports the growth of Ligilactobacillus murinus. CONCLUSION: Capsaicin-induced changes in the gut microbiota promote 5-ALA synthesis, leading to improved glycemic control. These findings suggest that dietary or probiotic interventions targeting gut microbiota, particularly Akkermansia muciniphila and 5-ALA, may offer promising strategies for managing glycemic disorders, including type 2 diabetes (T2D). Video Abstract.

Animals↗

Diet, mucosal architecture and epithelial cell production in the small intestine of specified-pathogen-free and conventional rats.

Upper jejunum and terminal ileum were examined in specified-pathogen-free (SPF), conventional and conventional after SPF rearing (ex-SPF) rats. The effect of 2 differential diets on the last 2 groups was examined. Ex-SPF rats had taller villi and deeper crypts than SPF rats, but similar crypt to villus ratios and cell production rates. Ex-SPF rats had similar crypt depth and jejunal villus height to conventional rats on the same diet, but taller ileal villi and a lower cell production rate. Even after 6-8 weeks, in a conventional environment, ex-SPF rat intestine was still not identical with conventional rat intestine. Diet had a significant effect on mucosal architecture, and a smaller effect on cell production rate. It is concluded that diet, microbiological status of colony of origin, and environment after weaning, can all affect mucosal architecture and epithelial cell production, and should be properly controlled in experimental studies.

Animal Feed↗

The microbiological and parasitological colonisation of specified-pathogen-free mice maintained in a conventional animal house.

2 groups of 44 specified-pathogen-free (SPF) mice, caged in groups of 4, were housed at weaning either in isolation in a building housing conventionally-reared animals, or in contact with those animals. 4 mice from each group were examined for microbiological flora and 4 for parasites at intervals for up to 90 days after transfer. Proscribed bacteria were isolated from the "in contact' group after 42 days and endoparasites were observed by 16 days and thereafter. No proscribed bacteria were isolated from the other group, although some endoparasites were observed by 16 days. Proscribed bacteria were shown to be present in the conventionally-reared animals at weaning and ecto- and endoparasites by day 16 and thereafter. It is suggested that it may be possible to maintain SPF animals outside a SPF Unit for short periods of time, and that with great care the animals remain free of proscribed microflora.

Animal Feed↗

Morphology and enzyme aktivity in rat small intestinal epithelium 6 and 12 hrs. after an alkylating agent (cyclophosphamide).

Six and twelve hours after a single i.p. dose of cyclophosphamide (100 mg/kg body weight) the activity of different "brush border enzymes" (maltase, sucrase lactase, alkaline phosphatase, gamma-glutamyl transferase) and of a lysosomal enzyme (acid phosphatase) did not change. In vivo absorption of galactose was not diminished by the treatment. The pattern of response to cyclophosphamide seems to be different in SPF and GF rats. The response of crypt epithelium (cell number, mitotic number, mitotic frequency) was more pronounced in the SPF rats, whereas the villus height only decreased in the GF rats.

Alkaline Phosphatase↗

Influence of antibody-mediated immune suppression on clinical, viral, and immune responses to swine influenza infection.

Antibody-mediated immune suppression occurred when newborn pigs with naturally acquired passive antibody were exposed to seine influenza virus. Frequency and relative ease of recovery of virus from nasal secretions were inversely related to the concentration of specific passive antibody existing at time of exposure. Severe overt respiratory signs during the acute stages of the disease were observed only in pigs with low passive antibody concentrations. The concentration of passive antibody at the time of exposure determined the immune status of the pig during the convalescent stage of disease. Infection could occur in the presence of high passive antibody concentrations, but the pig was not immunologically stimulated. Reexposure after the decay of passive antibody produced primary immune respone, severe clinical reinfection, and recovery of virus from nasal secretions for a period of time similar to that seen in pigs having their first exposure. Infection of newborn pigs with low passive antibody concentrations led to immunologic priming. A second exposure to virus produced a secondary immune response, mild clinical disease, and shortened time during which virus was recovered from nasal secretions. The relevance of these studies for the practice of vaccination or infections of the dam before parturition so that the neonate will have specific passive immunity is discussed.

Aerosols↗

Mycoplasmosis in specific-pathogen-free and conventional guinea pigs.

Normal female guinea pigs were examined for organisms of the order Mycoplasmatales. Thirty-nine isolations were made from nose or vagina of 108 guinea pigs. Seven isolates were identified as Mycoplasma caviae, 9 were unidentifiable mycoplasmas, and 23 were identified as nonsterol-requiring acholeplasmas.

Animals↗

The radiosensitivity of T and B lymphocytes in mice.

The radiosensitivity of T and B lymphocytes in spleens of specific pathogen-free C3Hf/HeMs male mice was studied by the direct and indirect immunofluorescence technique. It was found that the radiobiological parameters characterizing the survival curve of Bpsi lymphocytes were DO = 200 R and n = 1-00. The T lymphocytes, on the other hand, were shown to consist of two distinct subpopulations with respect to their radiosensitivity. The radiobiological parameters of the radiosensitive fraction of T lymphocytes were Dq = 185 R, DO =195 R and n = 2-50. The DO value of the radioresistant T lymphocyte subpopulation was practically unmeasurable. It was estimated that approximately 8 per cent of the T lymphocytes present in the spleen of normal C3Hf mice belonged to this radioresistant subpopulation.

Animals↗

[Histogenesis of the immune system of the "nude" mouse. III. Postnatal development of lymph nodes and spleen: a light microscopical study (author's transl)].

UNLABELLED: In neonatally thymectomized mice, the intermediate cortical zones of the lymph nodes as well as the central portions of the spleen follicles (=thymus dependent areas, TDA) are depleted of lymphocytes within a few weeks (Parrott et al., 1966). The TDA's in the lymphatic tissues of mice homozygous for the gene "nude" (nu/nu) contain also a very small number of lymphocytes. Since only a few developmental stages of the lymphatic tissues in nude mice have been studied, an investigation of the postnatal differentiation of their lymph nodes and spleen seemed worthwhile. MATERIALS AND METHODS: The mice (BALB/c) were maintained under specific pathogen-free (spf) conditions. Heterozygous (nu/ plus) females were mated with homozygous (nu/nu) males in order to obtain the homo- and heterozygous offsprings used in this study. Two nu/nu and two nu/ plus female mice were sacrificed at the following postnatal stages: day 1, 7, 14, 21, 35, 42, 49, 63 and 84, respectively. Newborn and 7 day old mice were fixed in toto in Bouin's solution and embedded in paraffin. From the other animals, spleen and mesenteric lymph nodes were removed and processed in an identical manner. Serial sections were cut at 5 mum and stained with hematoxylin and eosin. RESULTS: The mesenteric lymph nodes of the nu/ plus mice studied were indistinguishable from those of other mouse strains. In the nu/nu mouse, outer cortex and medulla of the mesenteric lymph nodes were found to develop as in normal (nu/ plus) animals, while the intermediate and deep cortex underwent characteristic changes...

Animals↗

Brain and spinal cord lesions in pigs inoculated with swine vesicular disease (UKG strain) virus and coxsackievirus B5.

Pigs inoculated intravenously with swine vesicular disease virus (UKG strain), those inoculated with coxsackievirus B5, and other pigs exposed by pen contact to the same viruses developed diffuse encephalomyelitis. Perivascular cuffing, with lymphocytes and formation of neuroglia cell foci, were most prominent in telencephalon, diencephalon, and mesencephalon. Encephalitis was of mild to severe intensity. Severity of lesions was more extensive and severe in the pigs exposed to swine vesicular disease virus. Pen contact exposure to either of the 2 viruses caused a more severe central nervous system reaction than did intravenous inoculation. The type and the distribution of lesions produced by the 2 viruses indicate that they may be related.

Animals↗