The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids.

Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.

Dopamine receptor D2 confers colonization resistance via microbial metabolites.

The gut microbiome has major roles in modulating host physiology. One such function is colonization resistance, or the ability of the microbial collective to protect the host against enteric pathogens1-3, including enterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, an attaching and effacing (AE) food-borne pathogen that causes severe gastroenteritis, enterocolitis, bloody diarrhea and acute renal failure4,5 (haemolytic uremic syndrome). Although gut microorganisms can provide colonization resistance by outcompeting some pathogens or modulating host defence provided by the gut barrier and intestinal immune cells6,7, this phenomenon remains poorly understood. Here, we show that activation of the neurotransmitter receptor dopamine receptor D2 (DRD2) in the intestinal epithelium by gut microbial metabolites produced upon dietary supplementation with the essential amino acid L-tryptophan protects the host against Citrobacter rodentium, a mouse AE pathogen that is widely used as a model for EHEC infection8,9. We further find that DRD2 activation by these tryptophan-derived metabolites decreases expression of a host actin regulatory protein involved in C. rodentium and EHEC attachment to the gut epithelium via formation of actin pedestals. Our results reveal a noncanonical colonization resistance pathway against AE pathogens that features an unconventional role for DRD2 outside the nervous system in controlling actin cytoskeletal organization in the gut epithelium. Our findings may inspire prophylactic and therapeutic approaches targeting DRD2 with dietary or pharmacological interventions to improve gut health and treat gastrointestinal infections, which afflict millions globally.

Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.

Iron is an essential trace element for both the host and resident microbes in the gut. In this study, iron was administered orally and parenterally to anemic piglets to investigate the role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity. We found that oral iron administration easily increased the abundance of Proteobacteria and Escherichia-Shigella, and decreased the abundance of Lactobacillus in the ileum. Furthermore, similar bacterial changes, namely an increase in Proteobacteria, Escherichia-Shigella, and Fusobacterium and a reduction in the Christensenellaceae_R-7_group, were observed in the colon of both iron-supplemented groups. Spearman's correlation analysis indicated that the changed Fusobacterium, Fusobacteria and Proteobacteria in the colon were positively correlated with hemoglobin, colon and spleen iron levels. Nevertheless, it was found that activated mTOR1 signaling, improved villous height and crypt depth in the ileum, enhanced immune communication, and increased protein expression of IL-22 and IL-10 in the colon of both iron-supplemented groups. In conclusion, the benefits of improved host iron outweigh the risks of altered gut microbiota for intestinal mucosal growth and immune regulation in treating iron deficiency anemia.

The Association between Caffeine Intake and the Colonic Mucosa-Associated Gut Microbiota in Humans-A Preliminary Investigation.

We examined the association between caffeine and coffee intake and the community composition and structure of colonic microbiota. A total of 34 polyp-free adults donated 97 colonic biopsies. Microbial DNA was sequenced for the 16S rRNA gene V4 region. The amplicon sequence variant was assigned using DADA2 and SILVA. Food consumption was ascertained using a food frequency questionnaire. We compared the relative abundance of taxonomies by low (<82.9 mg) vs. high (≥82.9 mg) caffeine intake and by never or <2 cups vs. 2 cups vs. ≥3 cups coffee intake. False discovery rate-adjusted p values (q values) <0.05 indicated statistical significance. Multivariable negative binomial regression models were used to estimate the incidence rate ratio and its 95% confidence interval of having a non-zero count of certain bacteria by intake level. Higher caffeine and coffee intake was related to higher alpha diversity (Shannon index p < 0.001), higher relative abundance of Faecalibacterium and Alistipes, and lower relative abundance of Erysipelatoclostridium (q values < 0.05). After adjustment of vitamin B2 in multivariate analysis, the significant inverse association between Erysipelatoclostridium count and caffeine intake remained statistically significant. Our preliminary study could not evaluate other prebiotics in coffee.

Siderophore Immunization Restricted Colonization of Adherent-Invasive Escherichia coli and Ameliorated Experimental Colitis.

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract and profound alterations to the gut microbiome. Adherent-invasive Escherichia coli (AIEC) is a mucosa-associated pathobiont that colonizes the gut of patients with Crohn's disease, a form of IBD. Because AIEC exacerbates gut inflammation, strategies to reduce the AIEC bloom during colitis are highly desirable. To thrive in the inflamed gut, Enterobacteriaceae acquire the essential metal nutrient iron by producing and releasing siderophores. Here, we implemented an immunization-based strategy to target the siderophores enterobactin and its glucosylated derivative salmochelin to reduce the AIEC bloom in the inflamed gut. Using chemical (dextran sulfate sodium) and genetic (Il10-/- mice) IBD mouse models, we showed that immunization with enterobactin conjugated to the mucosal adjuvant cholera toxin subunit B potently elicited mucosal and serum antibodies against these siderophores. Siderophore-immunized mice exhibited lower AIEC gut colonization, diminished AIEC association with the gut mucosa, and reduced colitis severity. Moreover, Peyer's patches and the colonic lamina propria harbored enterobactin-specific B cells that could be identified by flow cytometry. The beneficial effect of siderophore immunization was primarily B cell-dependent because immunized muMT-/- mice, which lack mature B lymphocytes, were not protected during AIEC infection. Collectively, our study identified siderophores as a potential therapeutic target to reduce AIEC colonization and its association with the gut mucosa, which ultimately may reduce colitis exacerbation. Moreover, this work provides the foundation for developing monoclonal antibodies against siderophores, which could provide a narrow-spectrum strategy to target the AIEC bloom in Crohn's disease patients. IMPORTANCE Adherent-invasive Escherichia coli (AIEC) is abnormally prevalent in patients with ileal Crohn's disease and exacerbates intestinal inflammation, but treatment strategies that selectively target AIEC are unavailable. Iron is an essential micronutrient for most living organisms, and bacterial pathogens have evolved sophisticated strategies to capture iron from the host environment. AIEC produces siderophores, small, secreted molecules with a high affinity for iron. Here, we showed that immunization to elicit antibodies against siderophores promoted a reduction of the AIEC bloom, interfered with AIEC association with the mucosa, and mitigated colitis in experimental mouse models. We also established a flow cytometry-based approach to visualize and isolate siderophore-specific B cells, a prerequisite for engineering monoclonal antibodies against these molecules. Together, this work could lead to a more selective and antibiotic-sparing strategy to target AIEC in Crohn's disease patients.

Beneficial Effects of Linseed Supplementation on Gut Mucosa-Associated Microbiota in a Physically Active Mouse Model of Crohn's Disease.

The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn's disease (CD). The aim of this study was to assess the effects of rebalancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Paraprevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect.

Postbiotic effects of Lactobacillus fermentate on intestinal health, mucosa-associated microbiota, and growth efficiency of nursery pigs challenged with F18+Escherichia coli.

This study determined the supplemental effects of Lactobacillus fermentate (LBF, Adare Biome, France) on intestinal health and prevention of postweaning diarrhea caused by F18+Escherichia coli in nursery pigs. Sixty-four weaned pigs (6.6 ± 0.7 kg body weight) were allotted in a randomized complete block design to four treatments: NC: no challenge/no supplement; PC: E. coli challenge/no supplement; AGP: E. coli challenge/bacitracin (30 g/t feed); and PBT: E. coli challenge/LBF (2 kg/t feed). Bacitracin methylene disalicylate (BMD) was used as a source of bacitracin. On day 7, challenged groups were orally inoculated with F18+E. coli (2.4 × 1010 CFU), whereas NC received sterile saline solution. Growth performance was analyzed weekly, and pigs were euthanized at the end of 28 d feeding to analyze intestinal health. Data were analyzed using the Mixed procedure of SAS 9.4. During the post-challenge period, PC tended to decrease (P = 0.067) average daily gain (ADG) when compared with NC, whereas AGP increased (P < 0.05) when compared with PC; PBT tended to increase (P = 0.081) ADG when compared with PC. The PC increased fecal score (P < 0.05) during day 7 to 14 when compared with NC, whereas AGP decreased it (P < 0.05) during day 14 to 21 when compared with PC. The PC increased (P < 0.05) protein carbonyl, crypt cell proliferation, and the relative abundance of Helicobacter rodentium when compared with NC. However, AGP decreased (P < 0.05) crypt cell proliferation and H. rodentium and increased (P < 0.05) villus height, Bifidobacterium boum, Pelomonas spp., and Microbacterium ginsengisoli when compared with PC. The PBT reduced (P < 0.05) crypt cell proliferation and H. rodentium and increased (P < 0.05) Lactobacillus salivarius and Propionibacterium acnes when compared with PC. At the genus level, AGP and PBT increased (P < 0.05) the alpha diversity of jejunal mucosa-associated microbiota in pigs estimated with Chao1 richness estimator when compared with PC. Collectively, F18+E. coli reduced growth performance by adversely affecting microbiota and intestinal health. The LBF and BMD improved growth performance, and it was related to the enhanced intestinal health and increased diversity and abundance of beneficial microbiota in pigs challenged with F18+E. coli.

Newly weaned pigs are susceptible to multiple stressors that may lead to postweaning diarrhea, thereby causing significant economic losses in the swine industry. Enterotoxigenic Escherichia coli strains are the major agents causing diarrhea in newly weaned pigs. Subtherapeutic antibiotics have been employed by producers around the world to mitigate this issue. However, the use of antibiotics as growth promoters has become a public health concern because of microbial resistance. This study used Lactobacillus fermentate (LBF) as a postbiotic to help maintain healthy microbiota on the intestinal mucosa and to prevent postweaning diarrhea caused by E. coli F18+. Therefore, the aim of this study was to evaluate the effects of dietary supplementation of LBF on intestinal microbiota, intestinal health, and prevention of postweaning diarrhea caused by a challenge with E. coli F18+ in newly weaned pigs. Our model confirmed that the E. coli F18+ reduced growth performance by causing diarrhea, disruption of the microbiota composition, and increased immune response and oxidative stress in the small intestine of newly weaned pigs. Lactobacillus fermentate improved growth performance, and it was related to enhanced intestinal health and increased microbiota diversity in E. coli F18+-challenged pigs.

Physiologically Inspired Mucin Coated Escherichia coli Nissle 1917 Enhances Biotherapy by Regulating the Pathological Microenvironment to Improve Intestinal Colonization.

The delivery of probiotics to the microbiota is a promising method to prevent and treat diseases. However, oral probiotics will suffer from gastrointestinal insults, especially the pathological microenvironment of inflammatory diseases such as reactive oxygen species (ROS) and the exhausted mucus layer, which can limit their survival and colonization in the intestinal tract. Inspired by the fact that probiotics colonized and grew in the mucus layer under physiological conditions, we developed a strategy for a super probiotic (EcN@TA-Ca2+@Mucin) coated with tannic acid and mucin via layer-by-layer technology. We demonstrated that mucin endows probiotics with superior resistance to the harsh environment of the gastrointestinal tract and with strong adhesiveness to the intestine through its interaction with mucus, which enhanced colonization and growth of probiotics in the mucus layer without removing the coating. Moreover, EcN@TA-Ca2+@Mucin can distinctly down-regulate inflammation with ROS scavenging and reduce the side effects of bacterial translocation in inflammatory bowel diseases, increasing the abundance and diversity of the gut microflora. We envision that it is a powerful platform to improve the colonization of probiotics by regulating the pathological microenvironment, which is expected to provide an important perspective for applying the intestinal colonization of probiotics to treat a variety of diseases.

Zinc Exposure Promotes Commensal-to-Pathogen Transition in Pseudomonas aeruginosa Leading to Mucosal Inflammation and Illness in Mice.

The opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) is associated gastrointestinal (GI) inflammation and illness; however, factors motivating commensal-to-pathogen transition are unclear. Excessive zinc intake from supplements is common in humans. Due to the fact that zinc exposure enhances P. aeruginosa colonization in vitro, we hypothesized zinc exposure broadly activates virulence mechanisms, leading to inflammation and illness. P. aeruginosa was treated with excess zinc and growth, expression and secretion of key virulence factors, and biofilm production were determined. Effects on invasion, barrier function, and cytotoxicity were evaluated in Caco-2 cells co-cultured with P. aeruginosa pre-treated with zinc. Effects on colonization, mucosal pathology, inflammation, and illness were evaluated in mice infected with P. aeruginosa pre-treated with zinc. We found the expression and secretion of key virulence factors involved in quorum sensing (QS), motility (type IV pili, flagella), biosurfactants (rhamnolipids), toxins (exotoxin A), zinc homeostasis (CzcR), and biofilm production, were all significantly increased. Zinc exposure significantly increased P. aeruginosa invasion, permeability and cytotoxicity in Caco-2 cells, and enhanced colonization, inflammation, mucosal damage, and illness in mice. Excess zinc exposure has broad effects on key virulence mechanisms promoting commensal-to-pathogen transition of P. aeruginosa and illness in mice, suggesting excess zinc intake may have adverse effects on GI health in humans.

BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities.

Nicotinamide riboside (NR) is one of the orally bioavailable NAD+ precursors and has been demonstrated to exhibit beneficial effects against aging and aging-associated diseases. However, the metabolic pathway of NR in vivo is not yet fully understood. Here, we demonstrate that orally administered NR increases NAD+ level via two different pathways. In the early phase, NR was directly absorbed and contributed to NAD+ generation through the NR salvage pathway, while in the late phase, NR was hydrolyzed to nicotinamide (NAM) by bone marrow stromal cell antigen 1 (BST1), and was further metabolized by the gut microbiota to nicotinic acid, contributing to generate NAD+ through the Preiss-Handler pathway. Furthermore, we report BST1 has a base-exchange activity against both NR and nicotinic acid riboside (NAR) to generate NAR and NR, respectively, connecting amidated and deamidated pathways. Thus, we conclude that BST1 plays a dual role as glycohydrolase and base-exchange enzyme during oral NR supplementation.

Inulin-grown Faecalibacterium prausnitzii cross-feeds fructose to the human intestinal epithelium.

Many chronic diseases are associated with decreased abundance of the gut commensal Faecalibacterium prausnitzii. This strict anaerobe can grow on dietary fibers, e.g., prebiotics, and produce high levels of butyrate, often associated to epithelial metabolism and health. However, little is known about other F. prausnitzii metabolites that may affect the colonic epithelium. Here, we analyzed prebiotic cross-feeding between F. prausnitzii and intestinal epithelial (Caco-2) cells in a "Human-oxygen Bacteria-anaerobic" coculture system. Inulin-grown F. prausnitzii enhanced Caco-2 viability and suppressed inflammation- and oxidative stress-marker expression. Inulin-grown F. prausnitzii produced excess butyrate and fructose, but only fructose efficiently promoted Caco-2 growth. Finally, fecal microbial taxonomy analysis (16S sequencing) from healthy volunteers (n = 255) showed the strongest positive correlation for F. prausnitzii abundance and stool fructose levels. We show that fructose, produced and accumulated in a fiber-rich colonic environment, supports colonic epithelium growth, while butyrate does not.

The Short-Chain Fatty Acids Propionate and Butyrate Augment Adherent-Invasive Escherichia coli Virulence but Repress Inflammation in a Human Intestinal Enteroid Model of Infection.

Short-chain fatty acids (SCFAs), which consist of six or fewer carbons, are fermentation products of the bacterial community that inhabits the intestine. Due to an immunosuppressive effect on intestinal tissue, they have been touted as a therapeutic for inflammatory conditions of the bowel. Here, we study the impact of acetate, propionate, and butyrate, the three most abundant SCFAs in the intestine, on gene expression in the intestinal pathobiont adherent-invasive Escherichia coli. We pair this with adherence, invasion, and inflammation in Caco-2 and human intestinal enteroid (HIE)-derived monolayer models of the intestinal epithelium. We report that propionate and butyrate upregulate transcription of adherent-invasive Escherichia coli (AIEC) flagellar synthesis genes and decrease expression of capsule assembly and transport genes. These changes are predicted to augment AIEC invasiveness. In fact, SCFA supplementation increases AIEC adherence to and invasion of the Caco-2 monolayer but has no effect on these parameters in the HIE model. We attribute this to the anti-inflammatory effect of propionate and butyrate on HIEs but not on Caco-2 cells. We conclude that the potential of SCFAs to increase the virulence of intestinal pathogens should be considered in their use as anti-inflammatory agents. IMPORTANCE The human terminal ileum and colon are colonized by a community of microbes known as the microbiota. Short-chain fatty acids (SCFAs) excreted by bacterial members of the microbiota define the intestinal environment. These constitute an important line of communication within the microbiota and between the microbiota and the host epithelium. In inflammatory conditions of the bowel, SCFAs are often low and there is a preponderance of a conditionally virulent bacterium termed adherent-invasive Escherichia coli (AIEC). A connection between SCFA abundance and AIEC has been suggested. Here, we study AIEC in monoculture and in coculture with human intestinal enteroid-derived monolayers and show that the SCFAs propionate and butyrate increase expression of AIEC virulence genes while concurrently bolstering the intestinal epithelial barrier and reducing intestinal inflammation. While these SCFAs have been promoted as a therapy for inflammatory bowel conditions, our findings demonstrate that their effect on bacterial virulence must be considered.

Intraperitoneal supplementation of iron alleviates dextran sodium sulfate-induced colitis by enhancing intestinal barrier function.

Iron supplementation is necessary for the treatment of anemia, one of the most frequent complications in inflammatory bowel disease (IBD). However, oral iron supplementation leads to an exacerbation of intestinal inflammation. Gut barrier plays a key role in the pathogenesis of IBD. The aim of this study was to characterize the interrelationship between systemic iron, intestinal barrier and the development of intestinal inflammation in a dextran sulfate sodium (DSS) induced experimental colitis mice model. We found that DSS-treated mice developed severe inflammation of colon, but became much healthy when intraperitoneal injection with iron. Iron supplementation alleviated colonic and systemic inflammation by lower histological scores, restorative morphology of colonic villi, and reduced expression of pro-inflammatory cytokines. Moreover, intraperitoneal supplementation of iron enhanced intestinal barrier function by upregulating the colonic expressions of tight junction proteins, restoring intestinal immune homeostasis by regulating immune cell infiltration and T lymphocyte subsets, and increasing mucous secretion of goblet cells in the colon. High-throughput sequencing of fecal 16 S rRNA showed that iron injection significantly increased the relative abundance of Bacteroidetes, which was suppressed in the gut microbiota of DSS-induced colitis mice. These results provided evidences supporting the protective effects of systemic iron repletion by intraperitoneal injection of iron on intestinal barrier functions. The finding highlights a novel approach for the treatment of IBD with iron injection therapy.

Traditional Chinese Medicine Ganshuang Granules Attenuate CCl4 -Induced Hepatic Fibrosis by Modulating Gut Microbiota.

Gut dysbiosis contributes to hepatic fibrosis. Emerging evidence revealed the major role of traditional Chinese medicine (TCM) in gut microbiota homeostasis. Here, we aimed to investigate the anti-fibrotic activity and underlying mechanism of ganshuang granules (GS), particularly regarding gut microbiota homeostasis. CCl4 -induced hepatic fibrosis models were allocated into 4 groups receiving normal saline (model), 1.0, 2.0, or 4.0 g/kg GS for 5 weeks. As result, GS treatment alleviated liver injury in CCl4 -induced hepatic fibrosis, presenting as decreases of the liver index, alanine aminotransferase, and aspartate transaminase. Histological staining and expression revealed that the enhanced oxidative stress, inflammatory and hepatic fibrosis in CCl4 -induced models were attenuated by GS. Immunohistochemical staining showed that tight junction-associated proteins in intestinal mucosa were up-regulated by GS. 16S rRNA sequencing showed that GS rebalanced the gut dysbiosis manifested as improving alpha and beta diversity of gut microbiota, reducing the ratio of Firmicutes to Bacteroidetes, and regulating the relative abundance of various bacteria. In summary, GS decreased the intestinal permeability and rebalanced the gut microbiota to reduce the oxidative stress and inflammation, eventually attenuating CCl4 -induced hepatic fibrosis.

Updating changes in human gut microbial communities associated with Clostridioides difficile infection.

Clostridioides difficile is the causative agent of antibiotic-associated diarrhea, a worldwide public health problem. Different factors can promote the progression of C. difficile infection (CDI), mainly altered intestinal microbiota composition. Microbial species belonging to different domains (i.e., bacteria, archaea, eukaryotes, and even viruses) are synergistically and antagonistically associated with CDI. This review was aimed at updating changes regarding CDI-related human microbiota composition using recent data and an integral approach that included the different microorganism domains. The three domains of life contribute to intestinal microbiota homeostasis at different levels in which relationships among microorganisms could explain the wide range of clinical manifestations. A holistic understanding of intestinal ecosystem functioning will facilitate identifying new predictive factors for infection and developing better treatment and new diagnostic tools, thereby reducing this disease's morbidity and mortality.

Protective Effects of Selenium Nanoparticle-Enriched Lactococcus lactis NZ9000 against Enterotoxigenic Escherichia coli K88-Induced Intestinal Barrier Damage in Mice.

Composite microecological agents have received widespread attention due to their advantageous properties, including safety, multiple effects, and low cost. This study was conducted to evaluate the protective effects of selenium (Se) nanoparticle (SeNP)-enriched Lactococcus lactis NZ9000 (L. lactis NZ9000-SeNPs) against enterotoxigenic Escherichia coli (ETEC) K88-induced intestinal barrier damage in C57BL/6 mice. The oral administration of L. lactis NZ9000-SeNPs significantly increased the villus height and the number of goblet cells in the ileum; reduced the levels of serum and ileal interleukin-1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ); and increased the activities of thioredoxin reductase (TrxR) and glutathione peroxidase (GSH-Px) compared with the ETEC K88-infected group not treated with L. lactis NZ9000-SeNPs. In addition, L. lactis NZ9000-SeNPs significantly attenuated the reduction of the expression levels of occludin and claudin-1, dysbiosis of the gut microbiome, and activation of the Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB)-mediated signaling pathway induced by ETEC K88. These findings suggested that L. lactis NZ9000-SeNPs may be a promising and safe Se supplement for food or feed additives. IMPORTANCE The beneficial effects of microecological agents have been widely proven. Se, which is a nutritionally essential trace element for humans and animals, is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant to anti-inflammatory effects. However, sodium selenite, a common addition form of Se in feed and food, has disadvantages such as strong toxicity and low bioavailability. We investigated the protective effects of L. lactis NZ9000-SeNPs against ETEC K88-induced intestinal barrier injury in C57BL/6 mice. Our results show that L. lactis NZ9000-SeNPs effectively alleviate ETEC K88-induced intestinal barrier dysfunction. This study highlights the importance of developing a promising and safe Se supplement for the substitution of sodium selenite applied in food, feed, and biomedicine.

Electroacupuncture interventions alleviates myocardial ischemia reperfusion injury through regulating gut microbiota in rats.

Electroacupuncture (EA) intervention has a remarkable cardioprotection against myocardial ischemia reperfusion injury (MIRI). Recently, it has been suggested that the gut microbiota plays an important role in regulating the progression and prognosis of MIRI. The purpose of this study was to illustrate the relationship between gut microbiota and cardioprotection of EA on MIRI. We conducted a MIRI model by ligating the left anterior descending coronary artery for 30 min followed by reperfusion in male Sprague Dawley rats, which then received 7 days of EA intervention. Echocardiography was employed to evaluate left ventricular function. Fecal samples were collected for microbial analysis by 16S rDNA high-throughput sequencing. Blood samples and myocardium were collected for inflammatory cytokine detection by enzyme linked immunosorbent assay (ELISA) and Western blot. Hematoxylin & eosin (HE) staining and immunofluorescence of ileum tissue were performed for intestinal damage evaluation. After 7 days of EA intervention, the left ventricular function was improved with significantly increased ejection fraction and fractional shortening. Furthermore, we found that EA intervention reversed the changed gut microbiota induced by MIRI, including Clostridiales, RF39, S24-7, Desulfovibrio, and Allobaculum, improved the impaired gut barrier, reduced the production and circulation of lipopolysaccharide (LPS), inhibited the level of interleukin 6 (IL-6) and interleukin 12 (IL-12) in periphery and decreased the expression of Toll like receptor 4 (TLR4) and IL-6 in myocardium. EA intervention could improve the impaired gut mucosal barrier and reduce the production and circulation of LPS after MIRI through regulating gut microbiota, thus inhibiting the circulation and myocardium inflammation and finally exerted the cardioprotective effect.

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis.

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1ß, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

Altered intestinal microflora and barrier injury in severe acute pancreatitis can be changed by zinc.

To investigate the effect of zinc (Zn) supplementation on intestinal microflora changes and bacterial translocation in rats with severe acute pancreatitis (SAP), the rats were divided into the sham surgery (SS), SAP, SS + Zn, and SAP + Zn groups. Saline (0.1 mL/100g) and 5% sodium taurocholate were injected into the pancreaticobiliary duct of the rats in the SS and SAP + Zn groups, respectively. Intraperitoneal injection of 5 mg/kg Zn was performed immediately after injecting saline or 5% sodium taurocholate into the rats in both groups. Serum amylase and Zn levels, plasma endogenous endotoxin, intestinal permeability, and the positive rate of intestinal bacterial translocation were detected, haematoxylin and eosin (H&E) staining was performed, and the pancreatic tissue scores were calculated for each group. In addition, immunohistochemical (IHC) staining was performed to evaluate the expression of IL-1ß and TNF-α. Real-time fluorescence quantitative PCR was used to quantify the gene copy numbers of Escherichia, Bifidobacterium, and Lactobacillus in the cecum. The levels of amylase and plasma endotoxin in the SAP group were significantly higher than those in the SS and SS + Zn groups. Intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were increased in the SAP group. However, the levels of amylase and plasma endotoxin were decreased as a result of zinc supplementation in the SAP group. The expression of IL-1ß and TNF-α was also reduced to a greater degree in the SAP + Zn group than in the SAP group. Moreover, alleviated intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were found in the SAP + Zn group. The results of real-time quantitative PCR showed that the gene copy number of Escherichia increased with time, and the gene copy numbers of Lactobacillus and Bifidobacterium decreased over time. Zn supplementation prevented the release of TNF-α and IL-1ß, alleviated intestinal permeability and endotoxemia, reduced bacterial translocation, and inhibited changes in pathogenic intestinal flora in rats with SAP.

Dietary bile acid supplementation reveals beneficial effects on intestinal healthy status of tongue sole (Cynoglossus semiliaevis).

The aim of this study was to investigate the effects of dietary bile acids (BAs) on intestinal healthy status of tongue sole in terms of immunity, antioxidant status, digestive ability, mucosal barrier-related genes expression and microbiota. Three experimental diets were prepared with BA levels at 0 mg/kg (CT), 300 mg/kg (BA1) and 900 mg/kg (BA2) in a commercial basal diet. Each diet was fed to three replicates with 120 fish (10.87 ± 0.32 g) in each tank. After an 8-week feeding trial, growth parameters were significantly enhanced in both BAs supplementary groups (P < 0.05), and compared with CT group, survival rate in BA2 group was significantly improved (P < 0.05). Intestinal lysozyme activity and contents of immunoglobulin M and complement 3 were significantly increased in both BAs supplementary groups (P < 0.05), suggesting an enhancement effect on the non-specific immune response. BAs inclusion also significantly improved intestinal antioxidant capabilities by increasing antioxidase activities and decreasing malondialdehyde levels. In addition, compared with CT group, intestinal digestive ability was substantially enhanced as indicated by the significantly increased lipase activity in BA2 group (P < 0.05) and significantly increased amylase activity in BA1 and BA2 groups (P < 0.05). Coincidentally, BAs inclusion significantly upregulated the relative expression of intestinal mucosal barrier-related genes (P < 0.05). Further, dietary BAs distinctly remodeled intestinal microbiota by decreased the abundance of some potential pathogenic bacteria. In conclusion, dietary BAs supplementation is an effective way to improve the intestinal healthy status of tongue sole.