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Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum-which is usually described as free of bacteria-became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ-deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.

Salmonella is the leading cause of bacterial foodborne zoonoses in humans. Thus, the development of strategies to control bacterial pathogens in poultry is essential. Peanut skins, a considerable waste by-product of the peanut industry is discarded and of little economic value. However, peanut skins contain identified polyphenolic compounds that have antimicrobial properties. Hence, we aim to investigate the use of peanut skins as an antibacterial feed additive in the diets of broilers to prevent the proliferation of Salmonella Enteritidis (SE). One hundred sixty male hatchlings (Ross 308) were randomly assigned to (i) peanut skin diet without SE inoculation (PS); (ii) peanut skin diet and SE inoculation (PSSE); (iii) control diet without SE inoculation (CON); and (iv) control diet with SE inoculation (CONSE). Feed intake and body weights were determined at weeks 0 and 5. On days 10 and 24 posthatch, three birds per pen (24 total) from each treatment group were euthanized, and the liver, spleen, small intestine, and ceca were collected. The weights of the liver, spleen, and ceca were recorded. Organ invasion was determined by counting SE colonies. Each pen served as an experimental unit and was analyzed by using a t test. Performance data were analyzed in a completely randomized design by using a general linear mixed model to evaluate differences. There were no significant differences (P > 0.05) in weekly average pen body weight, total feed consumption, bird weight gain, and feed conversion ratio between the treatment groups. There were no significant differences in SE CFU per gram for fecal, litter, or feed between the treatment groups CONSE and PSSE. However, for both fecal and litter, the PSSE treatment group tended (P ≤ 0.1) to have a lower Salmonella CFU per gram compared with the CONSE treatment group. The results indicate that peanut skins may have potential application as an antimicrobial feed additive to reduce the transmission or proliferation of SE in poultry environments or flocks. •Salmonella Enteritidis predominates within poultry production.•PS waste may be an effective feed additive to mitigate the proliferation of SE.•Dietary supplementation with PS reduced SE in fecal and litter samples (P ≤ 0.1).•PS may have potential application as an antimicrobial feed additive.

Aims/hypothesis We hypothesised that type 1 diabetic patients with established diabetic sensorimotor polyneuropathy (DSPN) would have segmental and/or pan-enteric dysmotility in comparison to healthy age-matched controls. We aimed to investigate the co-relationships between gastrointestinal function, degree of DSPN and clinical symptoms. Methods An observational comparison was made between 48 patients with DSPN (39 men, mean age 50 years, range 29–71 years), representing the baseline data of an ongoing clinical trial (representing a secondary analysis of baseline data collected from an ongoing double-blind randomised controlled trial investigating the neuroprotective effects of liraglutide) and 41 healthy participants (16 men, mean age 49 years, range 30–78) who underwent a standardised wireless motility capsule test to assess gastrointestinal transit. In patients, vibration thresholds, the Michigan Neuropathy Screening Instrument and Patient Assessment of Upper Gastrointestinal Symptom questionnaires were recorded. Results Compared with healthy controls, patients showed prolonged gastric emptying (299 ± 289 vs 179 ± 49 min; p =  0.01), small bowel transit (289 ± 107 vs 224 ± 63 min; p  = 0.001), colonic transit (2140, interquartile range [IQR] 1149–2799 min vs 1087, IQR 882–1650 min; p  = 0.0001) and whole-gut transit time (2721, IQR 1196–3541 min vs 1475 (IQR 1278–2214) min; p  < 0.0001). Patients also showed an increased fall in pH across the ileocaecal junction (−1.8 ± 0.4 vs −1.3 ± 0.4 pH; p  < 0.0001), which was associated with prolonged colonic transit ( r  = 0.3, p  = 0.001). Multivariable regression, controlling for sex, disease duration and glycaemic control, demonstrated an association between whole-gut transit time and total GCSI ( p =  0.02). Conclusions/interpretation Pan-enteric prolongation of gastrointestinal transit times and a more acidic caecal pH, which may represent heightened caecal fermentation, are present in patients with type 1 diabetes. The potential implication of delayed gastrointestinal transit on the bioavailability of nutrition and on pharmacotherapeutic and glycaemic control warrants further investigation. Trial registration EUDRA CT: 2013-004375-12

Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis. It produces dormant spores, which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment. In Bacillus subtilis, the sin locus coding SinR (113 aa) and SinI (57 aa) is responsible for sporulation inhibition. In B. subtilis, SinR mainly acts as a repressor of its target genes to control sporulation, biofilm formation, and autolysis. SinI is an inhibitor of SinR, so their interaction determines whether SinR can inhibit its target gene expression. The C. difficile genome carries two sinR homologs in the operon that we named sinR and sinR', coding for SinR (112 aa) and SinR' (105 aa), respectively. In this study, we constructed and characterized sin locus mutants in two different C. difficile strains R20291 and JIR8094, to decipher the locus's role in C. difficile physiology. Transcriptome analysis of the sinRR' mutants revealed their pleiotropic roles in controlling several pathways including sporulation, toxin production, and motility in C. difficile. Through various genetic and biochemical experiments, we have shown that SinR can regulate transcription of key regulators in these pathways, which includes sigD, spo0A, and codY. We have found that SinR' acts as an antagonist to SinR by blocking its repressor activity. Using a hamster model, we have also demonstrated that the sin locus is needed for successful C. difficile infection. This study reveals the sin locus as a central link that connects the gene regulatory networks of sporulation, toxin production, and motility; three key pathways that are important for C. difficile pathogenesis.

Mesalamine serves as the gold standard in treating ulcerative colitis. However, its precise mechanism(s) of action remains unclear. Here, we show that mesalamine treatment rapidly decreases polyphosphate levels in diverse bacteria, including members of the human gut microbiome. This decrease sensitizes bacteria towards oxidative stress, reduces colonization and attenuates persister cell and biofilm formation, suggesting that mesalamine aids in diminishing the capacity of bacteria to persist within chronically inflamed environments. Mesalamine, the gold-standard ulcerative colitis treatment, rapidly decreases polyphosphate levels in bacterial members of the gut microbiome, sensitizing them towards oxidative stress and reducing colonization and persister cell and biofilm formation.

How much does the microbiota influence the host's phenotype? Ridaura et al. ( 1241214 ; see the Perspective by Walker and Parkhill ) obtained uncultured fecal microbiota from twin pairs discordant for body mass and transplanted them into adult germ-free mice. It was discovered that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Moreover, obese-phenotype mice were invaded by members of the Bacteroidales from the lean mice, but, happily, the lean animals resisted invasion by the obese microbiota. Mice carrying gut bacteria from lean humans protect their cage mates from the effects of gut bacteria from fat humans. [Also see Perspective by Walker and Parkhill ] The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin’s microbiota (Ob) with mice containing the lean co-twin’s microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.

•Probiotics supplementation slowed weight gain in both the high-fat diet (HFD) and high-sucrose diet (HCD) groups.•An HFD is more likely to reduce gut microbiota diversity, whereas an HCD is more likely to alter the bacterial composition related to obesity.•Probiotics treatment can mitigate diet-induced obesity partly through modulating intestinal microbiota, especially in HCD-induced obesity. Gut microbiota plays a crucial role in host energy homeostasis, which is affected by both high-fat diets (HFDs) and high-sucrose diets (HCDs). Probiotics treatment can effectively modulate intestinal microbiota. However, it remains unclear whether probiotics can effectively improve HFD- and HCD-induced microbiota dysbiosis. Mice were fed either an HFD, HCD, or normal diet for 13 wk and administered probiotics during the last 4 wk of the diet. Fecal and cecal samples were collected and analyzed by high-throughput 16S ribosomal RNA sequencing. Body weight increased more in the HFD group compared with the HCD group. Probiotics supplementation slowed weight gain in both the HFD and HCD groups. Both the HFD and HCD reduced microbial diversity, abundance of butyric acid–producing bacteria, and some other beneficial bacteria, including Lactobacillus, Clostridium sensu stricto, Prevotella, and Alloprevotella, but increased conditional pathogenic bacteria, such as Bacteroides, Alistipes, and Anaerotruncus. Probiotics markedly restored the proportions of bacteria affected in the HFD and HCD groups and increased the abundance of microbiota negatively associated with obesity, including Bifidobacterium, Lactococcus, and Akkermansia. In addition, Oscillibacter, Escherichia/Shigella, Acinetobacter, and Blautia significantly increased in the HCD group; Allobaculum, Olsenella, and Ruminococcus were significantly changed in the HFD group. HCD-induced microbiota dysbiosis was more susceptible to probiotics treatment compared with the HFD. Probiotics treatment can mitigate diet-induced obesity partly through modulating intestinal microbiota, especially in HCD-induced obesity.

Oral-vaccine-induced IgA cross-links growing bacteria into clonal aggregates, inhibiting pathogenesis, adaption and the spread of antimicrobial resistance genes. Clumping antibody protects gut Immunoglobulin A (IgA) is a key component in the body's first line of defence against many infections, but the physical processes that drive its protective function in the gut are poorly defined. Kathrin Moor et al . show that IgA protects against Salmonella infection in the intestines of mice by enchaining the progeny of dividing bacteria into clonal or oligoclonal clumps. This clumping mechanism enables IgA to directly disarm potentially invasive species and prevent bacterial invasion, while avoiding immune processes that could cause damage to the host. Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues (‘immune exclusion’) 1 , 2 , 3 . IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium ( S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (≥10 8 non-motile bacteria per gram). In typical infections, much lower densities 4 , 5 (10 0 –10 7 colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo : IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo . Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.

The high susceptibility of neonates to infections has been assumed to be due to immaturity of the immune system, but the mechanism remains unclear. By colonizing adult germ-free mice with the cecal contents of neonatal and adult mice, we show that the neonatal microbiota is unable to prevent colonization by two bacterial pathogens that cause mortality in neonates. The lack of colonization resistance occurred when Clostridiales were absent in the neonatal microbiota. Administration of Clostridiales, but not Bacteroidales, protected neonatal mice from pathogen infection and abrogated intestinal pathology upon pathogen challenge. Depletion of Clostridiales also abolished colonization resistance in adult mice. The neonatal bacteria enhanced the ability of protective Clostridiales to colonize the gut.

Quercetin, a ubiquitous flavonoid, is known to have antibacterial effects. The purpose of this study was to investigate the effect of quercetin on cecal microbiota of Arbor Acre (AA) broiler chickens in vivo and the bacteriostatic effect and antibacterial mechanism of quercetin in vitro. In vivo, 480 AA broilers (1 day old) were randomly allotted to four treatments (negative control and 0.2, 0.4, or 0.6 g of quercetin per kg of diet) for 42 days. Cecal microbial population and distribution were measured at the end of the experiment. The cecal microflora in these broilers included Proteobacteria, Fimicutes, Bacteroidetes, and Deferribacteres. Compared with the negative control, quercetin significantly decreased the copies of Pseudomonas aeruginosa ( P < 0.05), Salmonella enterica serotype Typhimurium ( P < 0.01), Staphylococcus aureus ( P < 0.01), and Escherichia coli ( P < 0.01) but significantly increased the copies of Lactobacillus ( P < 0.01), Bifidobacterium ( P < 0.01), and total bacteria ( P < 0.01). In vitro, we investigated the bacteriostatic effect of quercetin on four kinds of bacteria ( E. coli, P. aeruginosa, S. enterica Typhimurium, and S. aureus) and the antibacterial mechanism of quercetin in E. coli and S. aureus. The bacteriostatic effect of quercetin was stronger on gram-positive bacteria than on gram-negative bacteria. Quercetin damaged the cell walls and membranes of E. coli (at 50 × MIC) and S. aureus (at 10 × MIC). Compared with the control, the activity of the extracellular alkaline phosphatase and β-galactosidase and concentrations of soluble protein in E. coli and S. aureus were significantly increased (all P < 0.01), and the activity of ATP in S. aureus was significantly increased ( P < 0.01); however, no significant change in ATP activity in E. coli was observed ( P > 0.05). These results suggest that quercetin has potential as an alternative antibiotic feed additive in animal production.