2′-Fucosyllactose Ameliorates Oxidative Stress Damage in d-Galactose-Induced Aging Mice by Regulating Gut Microbiota and AMPK/SIRT1/FOXO1 Pathway

The imbalance of reactive oxygen species is the main cause in aging, accompanied by oxidative stress. As the most abundant in human milk oligosaccharides (HMOs), 2′-Fucosyllactose (2′-FL) has been confirmed to have great properties in immunity regulation and anti-inflammatory. The research on 2′-FL is focused on infants currently, while there is no related report of 2′-FL for the elderly. A d-galactose-induced accelerated aging model was established to explore the protective effect of 2′-FL on the intestines and brain in mice. In this study, 2′-FL significantly reduced oxidative stress damage and inflammation in the intestines of aging mice, potentially by regulating the sirtuin1 (SIRT1)-related and nuclear factor E2-related factor 2 (Nrf2) pathways. In addition, 2′-FL significantly improved the gut mucosal barrier function and increased the content of short-chain fatty acids (SCFAs) in the intestine. The gut microbiota analysis indicated that 2′-FL mainly increased the abundance of probiotics like Akkermansia in aging mice. Moreover, 2′-FL significantly inhibited apoptosis in the brains of aging mice, also increasing the expression of SIRT1. These findings provided a basis for learning the benefits of 2′-FL in the aging process.

Endogenous Small Intestinal Microbiome Determinants of Transient Colonization Efficiency by Bacteria from Fermented Dairy Products; A Randomized Controlled Trial

BackgroundThe effects of fermented food consumption on the small intestine microbiome and its role on host homeostasis are largely uncharacterized as our knowledge on intestinal microbiota relies mainly on faecal samples analysis. We investigated changes in the small intestinal microbial composition and functionality, short chain fatty acid (SCFA) profiles, and on the gastro-intestinal (GI) permeability in ileostomy subjects upon the consumption of fermented milk products.ResultsWe report the results from a randomized, cross-over, explorative study where 16ileostomy subjects underwent 3, 2-week interventions periodsin which they daily consumed either milk fermented by Lacticaseibacillus rhamnosus CNCM I-3690, or milk fermented by Streptococcus thermophilus CNCM I-1630 and Lactobacillus delbrueckii subsp. bulgaricus CNCM I-1519, or a chemically acidified milk (placebo). Weperformed metataxonomic, metatranscriptomic analysis and SCFA profiling of ileostomy effluents as well as a sugar permeability test andto investigate the microbiome impact of these interventions and their potential effect on mucosal barrier function. Consumption of the intervention products significantly impacted the small intestinal microbiome composition and functionality but did not affect the SCFA levels in ileostoma effluent, or the gastro-intestinal permeability. Theimpact on microbiome composition was highly personalized,andwe identified the poorly characterized bacterial family, Peptostreptococcaceae, to be positively associated with low abundance of the ingested bacteria. Activity profiling of the microbiota revealed that carbon- versus amino acid-derived energy metabolism of the endogenous microbiome could be responsible for the individual-specific intervention effects on the small intestine microbiome composition and function.ConclusionsThe ingested bacteria are the main drivers of the intervention effect on the small intestinal microbiota composition. Their transient abundance level is highly personalized and influenced by the energy metabolism of the ecosystem that is reflected by its microbial composition (http://www.clinicaltrials.gov, ID NCT NCT02920294).

Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis

Evodiamine (EVO), an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth.、Evodia rutaecarpa (Juss.) Benth. Var. bodinieri (Dode) Huang or Evodia rutaecarpa (Juss.) Benth. Var. officinalis (Dode) Huang, has anti-inflammatory and anti-tumor activities. Our previous study found that EVO attenuates colitis by regulating gut microbiota and metabolites. However, little is known about its effect on colitis-associated cancer (CAC). In this study, the protective effects of EVO on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and tumor mice were observed, and the underlying potential mechanism was clarified. The results suggested that EVO ameliorated AOM/DSS-induced colitis by inhibiting the intestinal inflammation and improving mucosal barrier function. And EVO significantly reduced the number and size of AOM/DSS-induced colorectal tumors along with promoted apoptosis and inhibited proliferation of epithelial cell. Moreover, EVO promoted the enrichment of SCFAs-producing bacteria and reduced the levels of the pro-inflammatory bacteria, which contributes to the changes of microbiota metabolism, especially tryptophan metabolism. Furthermore, inflammatory response (like Wnt signaling pathway、Hippo signaling pathway and IL-17 signaling pathway) were effectively alleviated by EVO. Our study demonstrated that the protective therapeutic action of EVO on CAC is to inhibit the development of intestinal inflammation-cancer by regulating gut microbiota metabolites and signaling pathways of colon intestinal epithelial, which may represent a novel agent for colon cancer prevention via manipulation of gut microbiota.

Painong San, a Traditional Chinese Compound Herbal Medicine, Restores Colon Barrier Function on DSS-Induced Colitis in Mice

Objective. The intestinal barrier decreases in colitis and restores the integrity of the mucosal barriers that could be used for the treatment of colitis. Painong San (PNS), a traditional Chinese compound herbal medicine originally recorded in “Jingui Yaolve” by Zhongjing Zhang in the Later Han Dynasty, is often used in China and Japan to treat various purulent diseases including intestinal carbuncle. This study was to investigate the effect of PNS on mucosal barrier function in mice with DSS-induced colitis and its related mechanisms. Methods. BALB/C mice were given 3% DSS to induce colitis. The body weight and stool status of the mice were recorded daily, and the histopathological changes of the colon were observed after execution. The permeability of the intestinal mucosa was measured by fluorescein isothiocyanate-dextran 4000, the change of intestinal microbiota was measured by 16S rDNA, and the tight junction-related proteins and Muc-2 were investigated by immunohistochemical or immunofluorescence. The possible signaling pathways were detected by western blot. Results. Compared with the control group, the composition of the microbiota in the PNS group was close to that of the normal group, the number of goblet cells was improved, and the mucosal permeability was significantly reduced. PNS could upregulate the expression of tight junction-related proteins (ZO-1, claudin-1, and occludin) and Muc-2, and at the same time, regulate the Notch pathway. Conclusion. PNS could effectively improve the mucosal barrier function through multiple ways, including restoring the balance of intestine flora, enhancement of the mucous layer barrier, and mechanical barrier function. These protective effects may relate to inhibiting the Notch signaling pathway activated by DSS.

The Microbiome as a Key Regulator of Female Genital Tract Barrier Function

The microbiome, the collection of microbial species at a site or compartment, has been an underappreciated realm of human health up until the last decade. Mounting evidence suggests the microbiome has a critical role in regulating the female genital tract (FGT) mucosa’s function as a barrier against sexually transmitted infections (STIs) and pathogens. In this review, we provide the most recent experimental systems and studies for analyzing the interplay between the microbiome and host cells and soluble factors with an influence on barrier function. Key components, such as microbial diversity, soluble factors secreted by host and microbe, as well as host immune system, all contribute to both the physical and immunologic aspects of the FGT mucosal barrier. Current gaps in what is known about the effects of the microbiome on FGT mucosal barrier function are compared and contrasted with the literature of the gut and respiratory mucosa. This review article presents evidence supporting that the vaginal microbiome, directly and indirectly, contributes to how well the FGT protects against infection.

Protective effect of dexmedetomidine on intestinal mucosal barrier function in rats after cardiopulmonary bypass

Cardiopulmonary bypass can result in damage to the intestines, leading to the occurrence of systemic inflammatory response syndrome. Dexmedetomidine is reported to confer anti-inflammatory properties. Here, the purpose of this study is to investigate the effect of dexmedetomidine on the intestinal mucosa barrier damage in a rat model of cardiopulmonary bypass. It was observed that cardiopulmonary bypass greatly decreased the levels of hemodynamic parameters than SHAM group, whereas dexmedetomidine pretreatment in a cardiopulmonary bypass model rat prevented this reduction. Also, it showed that compared with control animals, cardiopulmonary bypass caused obvious mucosal damage, which was attenuated in dexmedetomidine + cardiopulmonary bypass group. The above findings were in line with that of dexmedetomidine pretreatment, which increased the expression of tight junction proteins, but it decreased the levels of DAO, D-LA, FABP2, and endotoxin. Moreover, the results demonstrated that due to pre-administration of dexmedetomidine, the level of pro-inflammatory factors was decreased, while the level of anti-inflammatory cytokine was increased. Also, it showed that dexmedetomidine suppressed TLR4/JAK2/STAT3 pathway that was activated by cardiopulmonary bypass. Together, these results revealed that dexmedetomidine pretreatment relieves intestinal microcirculation, attenuates intestinal damage, and inhibits the inflammatory response of cardiopulmonary bypass model rats, demonstrating that in CPB-induced damage of intestinal mucosal barrier function, dexmedetomidine pretreatment plays a protective role by inactivating TLR4/JAK2/STAT3-mediated inflammatory pathway.

Emodin Improves Intestinal Health and Immunity through Modulation of Gut Microbiota in Mice Infected by Pathogenic Escherichia coli O1

The effect of emodin on the intestinal mucosal barrier of a mouse E. coli O1-induced diarrhea model was observed. Following successful establishment of a diarrhea model, the mice were treated with drugs for seven days. Intestinal lesions and the shape and the number of goblet cells were assessed via hematoxylin-eosin and periodic-acid-Schiff staining, while changes in inflammatory factors, ultrastructure of the small intestine, expression of MUC-2, and changes in the intestinal microbiota were analyzed via RT-PCR, electron microscopy, immunofluorescence, and 16S rRNA sequencing. Examination showed that emodin ameliorated pathological damage to the intestines of diarrheic mice. RT-PCR indicated that emodin reduced TNF-α, IL-β, IL-6, MPO, and COX-2 mRNA levels in duodenal tissues and increased the levels of sIgA and MUC-2 and the number of goblet cells. Microbiome analysis revealed that Escherichia coli O1 reduced bacterial richness and altered the distribution pattern of bacterial communities at the phylum and order levels in cecum contents. Notably, pathogenic Clostridiales and Enterobacteriales were significantly increased in diarrheic mice. However, emodin reversed the trend. Thus, emodin protected against intestinal damage induced by E. coli O1 and improved intestinal mucosal barrier function in mice by increasing the abundance of beneficial intestinal microbiota and inhibiting the abundance of harmful bacteria, thereby alleviating diarrhea.

Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.