Gut Microbiota In Mice Research Articles

Low-frequency Transcranial Magnetic Stimulation Ameliorates Anhedonic Behaviors and Regulates the Gut Microbiome in Mice Exposed to Chronic Unpredictable Mild Stress.

This paper presents a preliminary study on whether low-frequency transcranial magnetic stimulation (LF-TMS) can modulate the gut microbiota in mice with chronic unpredictable mild stress (CUMS). Mice received LF-TMS (1 Hz, 20 mT) for 28 consecutive days under chronic unpredictable mild stress (CUMS). The composition of gut microbiota of stool samples were tested. CUMS caused significant changes in gut microbiotas, specifically in community diversity of gut microbiotas (P < .05). Compared with the stressed group mice, the Chao1 index (P < .05), Observed species index (P < .05), Faith's PD index (P < .05) and Shannon index (P < .05) of the LF-TMS treatment group were significantly increased. Furthermore, 1 Hz LF-TMS-treatment partially recovered chronic stress induced changes of microbiotas, such as the abundance of Chloroflexi, Actinobacteria. These results manifested that LF-TMS treatment can improve the anhedonic behaviors caused by CUMS in mice, which are connected with regulating the related intestinal microbial community disturbance, including species diversity, structure of gut microbiota, and species composition.

Lactobacillus plantarum104 Cell-free supernatant improved bile acid metabolism by regulating gut microbiota of high-fat diet mice

<em>Lactobacillus plantarum</em>104 Cell-free <em/>supernatant improved bile acid metabolism by regulating gut microbiota of high-fat diet mice

Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation

Hydrogen-rich water (HRW) is a beverage containing a high concentration of hydrogen that has been researched for its antioxidant, anti-apoptotic, and anti-inflammatory properties in asthma. This study investigates the potential therapeutic impact of HRW on the gut-lung axis. Using 16S rRNA and serum metabolomics, we examined changes in gut microbiota and serum metabolites in asthmatic mice after HRW intervention, followed by validation experiments. The findings revealed that HRW influenced gut microbiota by increasing Ligilactobacillus and Bifidobacterium abundance and enhancing the presence of indole-3-acetic acid (IAA), a microbially derived serum metabolite. Both in vivo and in vitro experiments showed that HRW's protective effects against airway inflammation in asthmatic mice may be linked to the gut microbiota, with IAA potentially playing a role in reducing asthmatic airway inflammation through the aryl hydrocarbon receptors (AhR) signaling pathway. In summary, HRW can modify gut microbiota, increase Bifidobacterium abundance, elevate microbial-derived IAA levels, and activate AhR, which could potentially alleviate inflammation in asthma.

The role of selenium intervention in gut microbiota homeostasis and gene function in mice with breast cancer on a high-fat diet.

This study aimed to investigate the effect of selenium on gut microbiota in mice with breast cancer under a high-fat diet. A total of 12 female BALB/c mice were randomly divided into two groups: 4 T1 + selenium+ high-fat diet group and 4 T1 + high-fat diet group. Mice were injected with 4 T1 cells on the right 4th mammary fat pad and kept on a high-fat diet. Fecal samples were collected, and DNA was extracted for metagenomic sequencing and bioinformatics analysis. Relevant target genes and pathways were annotated and metabolically analyzed to explore the intervention effect of selenium on breast cancer in the high-fat diet state. Selenium supplementation in the high-fat diet altered the composition and diversity of gut microbiota in mice with breast cancer. The gut microbial composition was significantly different in the selenium intervention group, with an increased abundance of Proteobacteria, Actinobacteria, and Verrucomicrobia phyla and species such as Helicobacter ganmani, Helicobacter japonicus, and Akkermansia muciniphila, while phyla, such as Bacteroidetes, Firmicutes, Deferribacteres, and Spirochaetes, and species, such as Prevotella sp. MGM2, Muribaculum intestinale, Lactobacillus murinus, and Prevotella sp. MGM1, were decreased. Functional analysis revealed differential expression of genes related to carbohydrate-active enzymes, pathogen-host interactions, cell communication, cell auto-induction, membrane transporters, and virulence factors. Furthermore, 37 COGs and 48 metabolites with rising metabolic potential in the selenium intervention group were predicted. Selenium alters the homeostasis of gut microbiota in mice with breast cancer on a high-fat diet, affecting their composition, abundance, and associated metabolism. These findings suggest that the mechanism involves interfering with gut microbiota homeostasis, leading to altered synthesis of tumor-associated proteins and fatty acids and inducing tumor cell apoptosis and pyroptosis.

Short-chain fatty acids ameliorate imiquimod-induced skin thickening and IL-17 levels and alter gut microbiota in mice: a metagenomic association analysis

Short-chain fatty acids (SCFAs) have been proposed to have anti-inflammatory effects and improve immune homeostasis. We aimed to examine the effects of SCFAs on skin phenotype, systemic inflammation, and gut microbiota in mice with psoriasis-like inflammation. Imiquimod (IMQ)-treated C57BL/6 mice served as the study model. We conducted a metagenomic association study of IMQ-mice treated with SCFAs or anti-IL-17 antibody using whole-genome shotgun sequencing. The associations among SCFA supplements, skin thickness, circulating inflammatory profiles, and fecal microbiota profiles were investigated. The microbiome study was performed using pipelines for phylogenetic analysis, functional gene analysis, and pathway analysis. In IMQ-treated mice, there were increases in skin thickness and splenic weight, as well as unique fecal microbial profiles. SCFAs ameliorated IMQ-induced skin thickening, splenic weight gain, and serum IL-17F levels, with results that were comparable with those receiving anti-IL-17 treatment. IMQ-treated mice receiving SCFAs had greater microbial diversity than mice treated with IMQ alone. SCFAs and anti-IL17 treatment were associated with alteration of gut microbiota, with increased prevalences of Oscillospiraceae and Lachnopiraceae and decreased prevalences of Muribaculaceae and Bacteroides, which have been predicted to be associated with increased glycan degradation, phenylalanine metabolism, and xylene degradation. SCFAs may mitigate IMQ-induced skin thickening and IL-17F levels and alter fecal microbiota profiles in IMQ-treated mice.

Microencapsulated rice bran alleviates hyperlipidemia induced by high-fat diet via regulating lipid metabolism and gut microbiota.

Hyperlipidemia has been suggested to be associated with dysregulation of lipid metabolism and gut microbiota. The present study prepared microencapsulated rice bran (MRB) with high stability based on in situ rice bran oil embedding and investigated the effects of MRB on lipid metabolism and gut microbiota in hyperlipidemic mice induced by high-fat diet (HFD). Results showed that compared to HFD fed mice, lipid levels in serum and hepatic lipid accumulation were reduced in mice fed with MRB, which was potentially associated with the fact that MRB decreased the expression of genes related to lipogenesis (Srebp1c, Acc, Hmgcr, and Fas) and increased the expression of genes related to lipid catabolism (Hsl, Atgl) and oxidation (Acox, Cpt1, Ucp1) (p<0.05). In gut, MRB supplementation significantly elevated the abundance of beneficial bacteria, such as Dubosiella and Faecalibaculum. In addition, significant increase in short-chain fatty acid was observed in mice from MRB groups when compared to HFD groups (p<0.05). Overall, this study suggested that MRB could alleviate the hyperlipidemia induced by HFD, which was related to the alteration of lipid metabolism and gut microbiota.

Polysaccharides of Floccularia luteovirens regulate intestinal immune response, and oxidative stress activity through MAPK/Nrf2/Keap1 signaling pathway in immunosuppressive mice

This study explores the novel immunomodulatory effects of polysaccharides from the rare Floccularia luteovirens, a fungus with significant potential yet unexplored bioactive components, traditionally used in Tibetan medicine. This study employs a wide array of analytical techniques, including HPGPC, HPLC, western blotting, ELISA, and 16S rRNA gene sequencing, to comprehensively investigate FLP1's effects. The main structure of FLP1 was characterized by IF-TR and NMR spectrometry. The structural backbone of FLP1 was →3,6)-β-D-Glcp-(1 → and →2,3)-α-D-Manp-(1→. After immunosuppressed mice treated with FLP1, the findings demonstrated that FLP1 stimulated the production of secretory sIgA and secretion of cytokines (IL-4, TNF-α, and IFN-γ) in the intestine of Cy-treated mice, resulting in the activation of the MAPK pathway. Additionally, FLP1 protected oxidative stress by triggering Nrf2/Keap1 pathways and antioxidation enzymes (SOD, MDA, T-AOC, CAT, and GSH-Px). It also enhanced the intestinal barrier function by regulating the villous height ratio and expression of tight-junction protein. Furthermore, FLP1 remarkably reversed the gut microbiota dysbiosis in immunosuppressed mice by increasing the abundance of Oscilliospiraceae, and Lachnospiraceae, and altered the fecal metabolites by increasing LysoPE (0:0/18:0); 0:0/16:0; 18:1(11Z)/0:0, LysoPG (16:0/0:0), LysoPG 18:1 (2n) PE (14:0/20:1), echinenone, 2-(2-Nitroimidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide, and suberic acid which is closely related to the immunity function. These results suggested that FLP1 may regulate the intestinal immune response by modulating the gut microbiota and fecal metabolites in immunosuppressed mice thereby activating the immune system.

Lactobacillus gasseri enhance gut homeostasis in normal mice and alleviate symptoms in Salmonella typhimurium-infected mice via bacteriocin generation

Bacteriocins are a class of anti-microbial proteins or peptides produced by bacteria that have antimicrobial activity and are regarded as potential alternatives to antibiotics. Lactobacillus (L.) gasseri, which is a probiotic, can produce bacteriocins. In the present study, we determined the bacteriostatic ability and bacteriocin-producing species of four strains of L. gasseri and investigated the effects of gavage of different bacteriocin-producing L. gasseri, on serum biochemical indices, intestinal cytokines, and gut microbiota of normal mice, a total of 40 C57BL/6J mice were used in the above study, where the gavage L. gasseri group was given a dose of 109 CFU/d. The ability of different bacteriocin-producing L. gasseri, to alleviate the symptoms caused by Salmonella (S.) typhimurium infection was further investigated, and the key bacteriocins and potential mechanisms were discuss, a total of 48 C57BL/6J mice were used in the above study.The results showed that Helveticin J, Gassericin K7B, Acidocin B and Bacteriocin LS2-producing L. gasseri FJXPY47L6, and FGSYC2L2, and FHNFQ28L4 could significantly improve the symptoms caused by S. typhimurium infection, and the bacteriocin-producing L. gasseri FJXPY47L6, and FGSYC2L2. Bacteriocin LS2-producing FJXPY47L6 showed the greatest ability to alleviate symptoms caused by S. typhimurium infection. These effects are achieved through bacteriocin-producing modulation of intestinal cytokines, gut microbiota, and short-chain fatty acids.

Metabolism of quercitrin in the colon and its beneficial regulatory effects on gut microbiota.

Quercitrin is a dietary flavonoid widely found in plants with various physiological activities. However, whether quercitrin alters gut microbiota in vivo is not well understood. The aim of this study was to investigate metabolism of quercitrin in the colon and its regulation on gut microbiota in mice. Herein, 22 flavonoids related to quercitrin metabolism were identified based on ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Gas chromatography and 16S rDNA gene sequencing were used to investigate short-chain fatty acid (SCFA) content and diversity of composition of gut microbiota, respectively. The results showed that quercitrin significantly alters the beta-diversity of the gut microbiota, probiotics such as Akkermansia and Lactococcus were significantly increased, and the production of propanoate, isovalerate and hexanoate of the quercitrin group were enhanced significantly. The Spearman's association analysis provided evidence that Gardnerella and Akkermansia have obvious correlations with most of quercitrin metabolites and SCFAs. Quercitrin and its metabolites in the colon altered the structure of the mice gut microbiota and increased the content of SCFAs. Our experiments provide valuable insights into quercitrin research and application. © 2024 Society of Chemical Industry.

Gut-derived metabolite 3-methylxanthine enhances cisplatin-induced apoptosis via dopamine receptor D1 in a mouse model of ovarian cancer.

Platinum-based chemotherapy failure represents a significant challenge in the management of ovarian cancer (OC) and contributes to disease recurrence and poor prognosis. Recent studies have shed light on the involvement of the gut microbiota in modulating anticancer treatments. However, the precise underlying mechanisms, by which gut microbiota regulates the response to platinum-based therapy, remain unclear. Here, we investigated the role of gut microbiota on the anticancer response of cisplatin and its underlying mechanisms. Our results demonstrate a substantial improvement in the anticancer efficacy of cisplatin following antibiotic-induced perturbation of the gut microbiota in OC-bearing mice. 16S rRNA sequencing showed a pronounced alteration in the composition of the gut microbiome in the cecum contents following exposure to cisplatin. Through metabolomic analysis, we identified distinct metabolic profiles in the antibiotic-treated group, with a notable enrichment of the gut-derived metabolite 3-methylxanthine in antibiotic-treated mice. Next, we employed a strategy combining transcriptome analysis and chemical-protein interaction network databases. We identified metabolites that shared structural similarity with 3-methylxanthine, which interacted with genes enriched in cancer-related pathways. It is identified that 3-methylxanthinesignificantly enhances the effectiveness of cisplatin by promoting apoptosis both in vivo and in vitro. Importantly, through integrative multiomics analyses, we elucidated the mechanistic basis of this enhanced apoptosis, revealing a dopamine receptor D1-dependent pathway mediated by 3-methylxanthine. This study elucidated the mechanism by which gut-derived metabolite 3-methylxanthine mediated cisplatin-induced apoptosis. Our findings highlight the potential translational significance of 3-methylxanthine as a promising adjuvant in conjunction with cisplatin, aiming to improve treatment outcomes for OC patients.IMPORTANCEThe precise correlation between the gut microbiota and the anticancer effect of cisplatin in OC remains inadequately understood. Our investigation has revealed that manipulation of the gut microbiota via the administration of antibiotics amplifies the efficacy of cisplatin through the facilitation of apoptosis in OC-bearing mice. Metabolomic analysis has demonstrated that the cecum content from antibiotic-treated mice exhibits an increase in the levels of 3-methylxanthine, which has been shown to potentially enhance the therapeutic effectiveness of cisplatin by an integrated multiomic analysis. This enhancement appears to be attributable to the promotion of cisplatin-induced apoptosis, with 3-methylxanthine potentially exerting its influence via the dopamine receptor D1-dependent pathway. These findings significantly contribute to our comprehension of the impact of the gut microbiota on the anticancer therapy in OC. Notably, the involvement of 3-methylxanthine suggests its prospective utility as a supplementary component for augmenting treatment outcomes in patients afflicted with ovarian cancer.

The effect of testosterone on the gut microbiome in mice

The role of hormones in gut–brain crosstalk is largely elusive, but recent research supports specific changes in hormone levels correlated with the gut microbiota. An interesting but unstudied area in microbial endocrinology is the interplay between the microbiota and sex hormones. The aim of this study is to investigate the effect of testosterone and sex on the mouse gut microbiome. We use in vitro experiments to test direct effects of testosterone on bacteria in fecal samples collected from male and female mice pre- and post-puberty. Sex-specific microbial and metabolic differences surrounding puberty are also examined in vivo. We then explore effects of testosterone supplementation in vivo, characterizing microbiota and metabolomes of male and female mice. We detect sex-specific differences in microbiota and associated metabolites of mice post-puberty, but in vitro experiments reveal that testosterone only affects microbiota of fecal samples collected before puberty. Testosterone supplementation in vivo affects gut microbiota and metabolomes in both male and female mice. Taking our results from in vitro and in vivo experiments, we conclude that the shift in the microbiome after puberty is at least partially caused by the higher levels of sex hormones, mainly testosterone, in the host.

Dietary Pectin from Premna microphylla Turcz Leaves Prevents Obesity by Regulating Gut Microbiota and Lipid Metabolism in Mice Fed High-Fat Diet.

The present study was designed to investigate the protective effects of pectin extracted from Premna microphylla Turcz leaves (PTP) against high-fat-diet (HFD)-induced lipid metabolism disorders and gut microbiota dysbiosis in obese mice. PTP was made using the acid extraction method, and it was found to be an acidic pectin that had relative mole percentages of 32.1%, 29.2%, and 26.2% for galacturonic acid, arabinose, and galactose, respectively. The administration of PTP in C57BL/6J mice inhibited the HFD-induced abnormal weight gain, visceral obesity, and dyslipidemia, and also improved insulin sensitivity, as revealed by the improved insulin tolerance and the decreased glucose levels during an insulin sensitivity test. These effects were linked to increased energy expenditure, as demonstrated by the upregulation of thermogenesis-related protein UCP1 expression in the brown adipose tissue (BAT) of PTP-treated mice. 16S rRNA gene sequencing revealed that PTP dramatically improved the HFD-induced gut dysbiosis by lowering the ratio of Firmicutes to Bacteroidetes and the quantity of potentially harmful bacteria. These findings may provide a theoretical basis for us to understand the functions and usages of PTP in alleviating obesity.

Integration of microbiomics, metabolomics, and transcriptomics reveals the therapeutic mechanism underlying Fuzheng-Qushi decoction for the treatment of lipopolysaccharide-induced lung injury in mice

Ethnopharmacological relevanceFuzheng-Qushi decoction (FZQS) is a practical Chinese herbal formula for relieving cough and fever. Therefore, the action and specific molecular mechanism of FZQS in the treatment of lung injury with cough and fever as the main symptoms need to be further investigated. Aims of the studyTo elucidate the protective effects of FZQS against lung injury in mice and reveal its potential targets and key biological pathways for the treatment of lung injury based on transcriptomics, microbiomics, and untargeted metabolomics analyses. Materials and methodsLipopolysaccharide (LPS) was used to induce a mouse model of lung injury, followed by the administration of FZQS. ELISA was used to detect IL-1β, IL-6, IL-17A, IL-4, IL-10, and TNF-α, in mouse lung tissues. Macrophage polarization and neutrophil activation were measured by flow cytometry. RNA sequencing (RNA-seq) was applied to screen for differentially expressed genes (DEGs) in lung tissues. RT-qPCR and Western blot assays were utilized to validate key DEGs and target proteins in lung tissues. 16S rRNA sequencing was employed to characterize the gut microbiota of mice. Metabolites in the gut were analyzed using untargeted metabolomics. ResultsFZQS treatment significantly ameliorated lung histopathological damage, decreased pro-inflammatory cytokine levels, and increased anti-inflammatory cytokine levels. M1 macrophage levels in the peripheral blood decreased, M2 macrophage levels increased, and activated neutrophils were inhibited in mice with LPS-induced lung injury. Importantly, transcriptomic analysis showed that FZQS downregulated macrophage and neutrophil activation and migration and adhesion pathways by reversing 51 DEGs, which was further confirmed by RT-qPCR and Western blot analysis. In addition, FZQS modulated the dysbiosis of the gut microbiota by reversing the abundance of Corynebacterium, Facklamia, Staphylococcus, Paenalcaligenes, Lachnoclostridium, norank_f_Muribaculaceae, and unclassified_f_Lachnospiraceae. Meanwhile, metabolomics analysis revealed that FZQS significantly regulated tryptophan metabolism by reducing the levels of 3-Indoleacetonitrile and 5-Hydroxykynurenine. ConclusionFZQS effectively ameliorated LPS-induced lung injury by inhibiting the activation, migration, and adhesion of macrophages and neutrophils and modulating gut microbiota and its metabolites.

Sodium sulphate ameliorates hypercholesterolemia via the upregulation of Cyp7a1 in hepatocytes and alleviates hepatic insulin resistance via the downregulation of Trib3 in mice with high cholesterol diets.

Amelioration of hypercholesterolemia is essential for the treatment of atherosclerotic cardiovascular disease. Sodium sulphate is the effective component of mirabilite, which has been used in traditional Chinese medicine for the treatment of various diseases. In the present study, C57BL/6 mice were fed with a high-cholesterol diet (HCD) for 7 weeks and were treated with sodium sulphate in the last three of those weeks. Sodium sulphate significantly reduced the total cholesterol level and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in the serum of mice fed the HCD. In addition, cytochrome P450 7a1 and 39a1 were significantly upregulated in the livers of mice treated with sodium sulphate. Furthermore, tribbles pseudokinase 3 expression was significantly increased in the livers of mice fed the HCD, but was significantly reduced by sodium sulphate treatment. In terms of the insulin signaling pathway, the ratio of phosphorylated AKT to total AKT in the livers of mice fed the HCD was significantly lower compared with that of control mice fed a normal diet, but was significantly increased by sodium sulphate treatment. Sodium sulphate treatment also reduced the levels of fibroblast growth factor (FGF)15 in the ileum and inhibited the FGF15/FGF receptor 4-Klotho β/c-Jun N-terminal kinase/c-Jun signaling pathway in the livers of mice fed the HCD. In addition, sodium sulphate changed the composition of the gut microbiota of mice fed the HCD. In conclusion, sodium sulphate may mitigate hypercholesterolemia and hepatic insulin resistance in mice fed an HCD.

Male mice are susceptible to brain dysfunction induced by early-life acephate exposure.

Acephate is a widely used organophosphate insecticide. Exposure to endocrine-disrupting chemicals, such as acephate, can interfere with neurodevelopment in childhood, increasing the risk of higher brain dysfunction later in life. Furthermore, brain dysfunction may be related to chemical exposure-related disturbances in the gut microbiota. However, the effects of early acephate exposure on the brains of adult males and females as well as on the adult gut environment remain poorly understood. This study investigated the effects of perinatal acephate exposure on the central nervous system and gut microbiota of mice, including sex differences and environmentally relevant concentrations. C57BL/6 N pups were exposed to acephate (0, 0.3, 10, and 300 ppm) via the dam in their drinking water from embryonic day (E) 11.5 to postnatal day 14. We examined its effects on the central nervous system of adult males and females. In the male treatment group, impairments in learning and memory were detected. Immunohistochemical analysis revealed a decrease in SOX2-, NeuN-, DCX-, and GFAP-positive cells in the hippocampal dentate gyrus in males compared to the control group, whereas GFAP-positive cells were fewer in females. In addition, gut microbiota diversity was reduced in both sexes in the experimental group. Our study demonstrates that the effects of early-life exposure to acephate are more pronounced in males than in females and can lead to a lasting impact on adult behavior, even at low doses, and that the gut microbiota may reflect the brain environment.

Humid heat environment causes anxiety-like disorder via impairing gut microbiota and bile acid metabolism in mice

Climate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.

Intestinal epithelial Cldn-7 regulates intestinal inflammation by altering the gut microbiota

Background and aimTight junctions maintain gut homeostasis by forming a physical barrier that protects the gut from invasion by microbiota. Cldn-7 is an important component involved in this protection, but the relationship between Cldn-7, intestinal inflammation, and gut microbiota has not been clarified. Here, we hypothesize that Cldn-7 depletion affects intestinal inflammation by altering the gut microbiota. MethodsBased on the induced intestinal condition of Cldn-7 knockout mice (Cldn7fl/fl;villin-CreaERT2), we established the intestinal flora depletion model and colitis model by antibiotic drinking and feeding with dextran sodium sulfate (DSS). The environment of Cldn-7 gene deletion mice was changed by co-housing experiment. AB-PAS staining and Muc2 were used to detect the effect of co-housing and Cldn-7 deficiency on the mucus layer after flora depletion. qRT-PCR was used to detect the expression of intestinal inflammatory factors and AMPs in mice. Feces were collected and proportions of microbiota were analyzed by 16 S rRNA amplicon sequencing. ResultsMice in the co-housing experiment had altered intestinal microbiota, including diversity, composition, and functional prediction, compared to controls. Intestinal inflammation was restored to some extent following altered intestinal microbiota. The intestinal inflammation caused by Cldn-7 deficiency and susceptibility to DSS could be reduced after antibiotic administration compared to controls, in terms of phenotype, pathological changes, inflammatory factors, mucus barrier, and expression of AMPs. ConclusionsIn analyses of intestinal tissues, colitis induction, and gut microbiota in mice with intestinal disruption of Cldn-7, we found this protein to prevent intestinal inflammation by regulating the gut microbiota. Cldn-7might therefore be an important mediator of host–microbiome interactions. Our research has revealed that Cldn-7 plays an indispensable role in maintaining intestinal homeostasis by regulating the gut microbiota and impacting intestinal inflammation. These findings provide new insights into the pathogenesis of ulcerative colitis.

Termite Fungus Comb Polysaccharides Alleviate Hyperglycemia and Hyperlipidemia in Type 2 Diabetic Mice by Regulating Hepatic Glucose/Lipid Metabolism and the Gut Microbiota.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and dyslipidemia. The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.

Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice but not in chow-fed mice

Dietary lipids play an essential role in regulating the function of the gut microbiota and gastrointestinal tract, and these luminal interactions contribute to mediating host metabolism. Palmitic Acid Hydroxy Stearic Acids (PAHSAs) are a family of lipids with antidiabetic and anti-inflammatory properties, but whether the gut microbiota contributes to their beneficial effects on host metabolism is unknown. Here, we report that treating chow-fed female and male germ-free (GF) mice with PAHSAs improves glucose tolerance, but these effects are lost upon high fat diet (HFD) feeding. However, transfer of feces from PAHSA-treated, but not vehicle-treated, chow-fed conventional mice increases insulin sensitivity in HFD-fed GF mice. Thus, the gut microbiota is necessary for, and can transmit, the insulin-sensitizing effects of PAHSAs in HFD-fed GF male mice. Analyses of the cecal metagenome and lipidome of PAHSA-treated mice identified multiple lipid species that associate with the gut commensal Bacteroides thetaiotaomicron (Bt) and with insulin sensitivity resulting from PAHSA treatment. Supplementing live, and to some degree, heat-killed Bt to HFD-fed female mice prevented weight gain, reduced adiposity, improved glucose tolerance, fortified the colonic mucus barrier and reduced systemic inflammation compared to HFD-fed controls. These effects were not observed in HFD-fed male mice. Furthermore, ovariectomy partially reversed the beneficial Bt effects on host metabolism, indicating a role for sex hormones in mediating the Bt probiotic effects. Altogether, these studies highlight the fact that PAHSAs can modulate the gut microbiota and that the microbiota is necessary for the beneficial metabolic effects of PAHSAs in HFD-fed mice.

A neurotherapeutic approach with Lacticaseibacillus rhamnosus E9 on gut microbiota and intestinal barrier in MPTP-induced mouse model of Parkinson’s disease

The gut microbiota plays a crucial role in neural development and progression of neural disorders like Parkinson’s disease (PD). Probiotics have been suggested to impact neurodegenerative diseases via gut-brain axis. This study aims to investigate the therapeutic potential of Lacticaseibacillus rhamnosus E9, a high exopolysaccharide producer, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of PD. C57BL/6 mice subjected to MPTP were fed L. rhamnosus E9 for fifteen days and sacrificed after the last administration. Motor functions were determined by open-field, catalepsy, and wire-hanging tests. The ileum and the brain tissues were collected for ELISA, qPCR, and immunohistochemistry analyses. The cecum content was obtained for microbiota analysis. E9 supplementation alleviated MPTP-induced motor dysfunctions accompanied by decreased levels of striatal TH and dopamine. E9 also reduced the level of ROS in the striatum and decreased the DAT expression while increasing the DR1. Furthermore, E9 improved intestinal integrity by enhancing ZO-1 and Occludin levels and reversed the dysbiosis of the gut microbiota induced by MPTP. In conclusion, E9 supplementation improved the MPTP-induced motor deficits and neural damage as well as intestinal barrier by modulating the gut microbiota in PD mice. These findings suggest that E9 supplementation holds therapeutic potential in managing PD through the gut-brain axis.