Explore the vast range of titles available.

Lactobacillus species are the predominant vaginal microbiota found in healthy women of reproductive age and help to prevent pathogen infection by producing lactic acid, H 2 O 2 and anti-microbial compounds. Identification of novel vaginal Lactobacillus isolates that exhibit efficient colonisation and secrete anti- Candida factors is a promising strategy to prevent vulvovaginal candidiasis. The azole antifungal agents used to treat vulvovaginal candidiasis elicit adverse effects such as allergic responses and exhibit drug interactions. Candida strains with resistance to antifungal treatments are often reported. In this study, we isolated Lactobacillus species from healthy Korean women and investigated their antifungal effects against C . albicans in vitro and in vivo . Lactobacillus conditioned supernatant (LCS) of L . crispatus and L . fermentum inhibited C . albicans growth in vitro . A Lactobacillus -derived compound, which was not affected by proteolytic enzyme digestion and heat inactivation, inhibited growth and hyphal induction of C . albicans after adjustment to neutral pH. Combination treatment with neutral LCSs of L . crispatus and L . fermentum effectively inhibited propagation of C . albicans in a murine in vivo model of vulvovaginal candidiasis.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects. Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in individuals without obesity. Here, gut microbiome analysis using a biopsy-proven NAFLD cohort reveal distinct signatures of microbiome-metabolites associated with significant fibrosis in patients with NAFLD without obesity.

ObjectiveMetabolic syndrome (MetS) arises from complex interactions between host genetic and environmental factors. Although it is now widely accepted that the gut microbiota plays a crucial role in host metabolism, current knowledge on the effect of host genetics on specific gut microbes related to MetS status remains limited. Here, we investigated the links among host genetic factors, gut microbiota and MetS in humans.DesignWe characterised the gut microbial community composition of 655 monozygotic (n=306) and dizygotic (n=74) twins and their families (n=275), of which approximately 18% (121 individuals) had MetS. We evaluated the association of MetS status with the gut microbiota and estimated the heritability of each taxon. For the MetS-related and heritable taxa, we further investigated their associations with the apolipoprotein A-V gene (APOA5) single nucleotide polymorphism (SNP) rs651821, which is known to be associated with triglyceride levels and MetS.ResultsIndividuals with MetS had a lower gut microbiota diversity than healthy individuals. The abundances of several taxa were associated with MetS status; Sutterella, Methanobrevibacter and Lactobacillus were enriched in the MetS group, whereas Akkermansia, Odoribacter and Bifidobacterium were enriched in the healthy group. Among the taxa associated with MetS status, the phylum Actinobacteria, to which Bifidobacterium belongs, had the highest heritability (45.7%). Even after adjustment for MetS status, reduced abundances of Actinobacteria and Bifidobacterium were significantly linked to the minor allele at the APOA5 SNP rs651821.ConclusionsOur results suggest that an altered microbiota composition mediated by a specific host genotype can contribute to the development of MetS.

Faecalibacterium prausnitzii is a major commensal bacterium in the human gut. It produces short-chain fatty acids that promote intestinal health. However, the bacterium is extremely oxygen-sensitive, making it difficult to develop as a probiotic. To facilitate practical application of F. prausnitzii, we investigated factors that affect its growth and mammalian gut colonization. We evaluated cross-feeding interactions between F. prausnitzii and seven Bifidobacterium strains, and the anti-inflammatory properties of bacterial metabolites produced in co-culture, in vitro and in vivo. Co-culture of F. prausnitzii and Bifidobacterium catenulatum, with fructooligosaccharides as an energy source, resulted in the greatest viable cell-count and butyrate production increases. Further, the co-culture supernatant reduced the amount of proinflammatory cytokines produced by HT-29 cells and RAW 264.7 macrophages, an effect that was similar to that of butyrate. Furthermore, feeding mice both Faecalibacterium and Bifidobacterium enhanced F. prausnitzii gut colonization. Finally, feeding the co-culture supernatant decreased interleukin 8 levels in the colon and increased butyrate levels in the cecum in the dextran sodium sulfate-induced colitis mouse model. These observations indicate that the Faecalibacterium-Bifidobacterium co-culture exerts an anti-inflammatory effect by promoting F. prausnitzii survival and short-chain fatty acid production, with possible implications for the treatment of inflammatory bowel disease.

Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus biology. Among these phytochemicals, curcumin (CCM) was the most potent anti-noroviral phytochemical, followed by resveratrol (RVT). In a cell culture infection model, exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91% and 80%, respectively. To confirm the antiviral capability of CCM, we further evaluated its antiviral efficacy at various doses (0.25, 0.5, 0.75, 1, and 2 mg/mL) and durations (short-term: 10, 30, 60, and 120 min; long-term: 1, 3, 7, and 14 days). The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner. Additionally, we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line (HG23). Neither CCM nor RVT had a strong inhibitory effect on HuNoV replication, which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA. Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness.

Background Long-term intake of a Western diet (WD), characterized by a high-fat content and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms by which dietary changes contribute to IBD development remain unknown. Therefore, we examined the influence of long-term intake of a WD on intestinal inflammation and the mechanisms by which WD intake affects IBD development. Methods Mice fed normal diet or WD for 10 weeks, and bowel inflammation was evaluated through pathohistological and infiltrated inflammatory cell assessments. To understand the role of intestinal taste receptor type 1 member 3 (TAS1R3) in WD-induced intestinal inflammation, cultured enteroendocrine cells harboring TAS1R3, subjected to RNA interference or antagonist treatment, and Tas1r3 -deficient mice were used. RNA-sequencing, flow cytometry, 16S metagenomic sequencing, and bioinformatics analyses were performed to examine the involved mechanisms. To demonstrate their clinical relevance, intestinal biopsies from patients with IBD and mice with dextran sulfate sodium-induced colitis were analyzed. Results Our study revealed for the first time that intestinal TAS1R3 is a critical mediator of WD-induced intestinal inflammation. WD-fed mice showed marked TAS1R3 overexpression with hallmarks of serious bowel inflammation. Conversely, mice lacking TAS1R3 failed to exhibit inflammatory responses to WD. Mechanistically, intestinal transcriptome analysis revealed that Tas1r3 deficiency suppressed mTOR signaling, significantly increasing the expression of PPARγ (a major mucosal defense enhancer) and upregulating the expression of PPARγ target-gene (tight junction protein and antimicrobial peptide). The gut microbiota of Tas1r3 -deficient mice showed expansion of butyrate-producing Clostridia. Moreover, an increased expression of host PPARγ-signaling pathway proteins was positively correlated with butyrate-producing microbes, suggesting that intestinal TAS1R3 regulates the relationship between host metabolism and gut microflora in response to dietary factors. In cultured intestinal cells, regulation of the TAS1R3–mTOR–PPARγ axis was critical for triggering an inflammatory response via proinflammatory cytokine production and secretion. Abnormal regulation of the axis was observed in patients with IBD. Conclusions Our findings suggest that the TAS1R3–mTOR–PPARγ axis in the gut links Western diet consumption with intestinal inflammation and is a potential therapeutic target for IBD.

The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium , B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes— IL-17A , IRF4 , RORC , IL-21 , and IL-23R —in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.

Selenium and zinc are essential trace minerals for humans with various biological functions. In this study, selenium- and zinc-tolerant lactic acid bacteria (LAB) isolates were screened out from human fecal samples. Amongst three hundred LAB isolates, the Lactobacillus plantarum SeZi strain displayed the tolerance against selenium and zinc with the greatest biomass production and bioaccumulation of selenium and zinc. To further assess the characteristics of this strain, the lyophilized L. plantarum SeZi were prepared and administered to Institute of Cancer Research (ICR) mice. The mice were divided into four groups, provided with normal chow (Con), or normal chow supplemented with Na2SeO3 and ZnSO4∙7H2O (SZ), L. plantarum SeZi (Lp), or selenium- and zinc-enriched L. plantarum SeZi (SZ + Lp), respectively. After 4 weeks of oral administration, the concentrations of selenium and zinc in blood were significantly increased in the SZ + Lp group when compared to the control or SZ group (p < 0.05). The increased selenium level led to an enhanced glutathione peroxidase activity and decreased blood malondialdehyde level in the SZ + Lp group (p < 0.05). Meanwhile, the results of bacterial community and microbial metabolic pathway analysis via 16S rRNA gene amplicon sequencing showed that L. plantarum SeZi significantly promoted the utilization of selenocysteine, seleno-cystathionine and seleno-methionine in the selenocompounds metabolism. Here, the in vivo antioxidant capacities of the selenium- and zinc-enriched lactobacillus strain showed us the utilization of a unique probiotic as a Se/Zn supplement with high availability, low toxicity, and additional probiotic advantages.

Chronic alcohol consumption often induces hepatic steatosis but rarely causes severe inflammation in Kupffer cells (KCs) despite the increased hepatic influx of lipopolysaccharide (LPS), suggesting the presence of a veiled tolerance mechanism. In addition to LPS, the liver is affected by several gut-derived neurotransmitters through the portal blood, but the effects of catecholamines on KCs have not been clearly explored in alcohol-associated liver disease (ALD). Hence, we investigated the regulatory roles of catecholamine on inflammatory KCs under chronic alcohol exposure. We discovered that catecholamine levels were significantly elevated in the cecum, portal blood, and liver tissues of chronic ethanol-fed mice. Increased catecholamines induced mitochondrial translocation of cytochrome P450 2E1 in perivenous hepatocytes expressing the β2-adrenergic receptor (ADRB2), leading to the enhanced production of growth differentiation factor 15 (GDF15). Subsequently, GDF15 profoundly increased ADRB2 expression in adjacent inflammatory KCs to facilitate catecholamine/ADRB2-mediated apoptosis. Single-cell RNA sequencing of KCs confirmed the elevated expression of Adrb2 and apoptotic genes after chronic ethanol intake. Genetic ablation of Adrb2 or hepatic Gdf15 robustly decreased the number of apoptotic KCs near perivenous areas, exacerbating alcohol-associated inflammation. Consistently, we found that blood and stool catecholamine levels and perivenous GDF15 expression were increased in patients with early-stage ALD along with an increase in apoptotic KCs. Our findings reveal a novel protective mechanism against ALD, in which the catecholamine/GDF15 axis plays a critical role in KC apoptosis, and identify a unique neuro-metabo-immune axis between the gut and liver that elicits hepatoprotection against alcohol-mediated pathogenic challenges. Liver disease: Pathways converge to avert alcohol-induced damage The interplay between neurochemical, metabolic, and immunological processes helps to control inflammatory damage to the liver arising from chronic alcohol consumption. Catecholamine is a neurotransmitter that is also produced outside the brain, including by microbiome in the gut. Researchers in South Korea led by Won-Il Jeong of the Korea Advanced Institute of Science & Technology, Daejeon, and Won Kim at Seoul National University have shown how this molecule contributes to the protective response against alcohol-induced liver damage. Mice routinely dosed with alcohol produced high levels of catecholamine in their gut, which generated a metabolic stress response in a subset of liver cells. These stressed liver cells subsequently transmit signals to certain immune cells within the liver, causing those cells to self-destruct and thereby averting a damaging inflammatory response that could otherwise accelerate disease progression.

The cocktails of antibiotics are utilized to study the functions of microbiota. There have been studies on the alteration of not only the microbiota composition but also the host’s metabolism or immunity. However, the bacterial species associated with these altered physiologic markers are still unclear. Therefore, we supplied mice with drinking water containing ampicillin (AMP), vancomycin (VAN), neomycin (NEO), or metronidazole (MET) to observe the effect of each antibiotic on helper T cells and inflammation-related gene expression and metabolism, including amino acid metabolism and changes in gut microbiota. We observed major changes in gut microbiota in mice treated with AMP and VAN, respectively, immediately after administration. The abundance of the genera Parabacteroides and Akkermansia increased in the AMP and VAN groups, while Prevotella almost disappeared from both groups. The compositional changes in intestinal metabolites in the AMP and VAN groups were more distinct than those in the NEO and MET groups, which was similar to the microbiome results. In particular, the most distinct changes were observed in amino acid related metabolism in AMP and VAN groups; the amounts of phenylalanine and tyrosine were increased in the AMP group while those were decreased in the VAN group. The changed amounts of intestinal amino acids in each of the AMP and VAN groups were correlated with increases in the abundance of the genera Parabacteroides and Akkermansia in the AMP and VAN groups, respectively. The most distinctive changes in intestinal gene expression were observed in the ileum, especially the expression Th17-related genes such as rorgt, il17a, and il17f, which decreased dramatically in the guts of most of the antibiotic-treated groups. These changes were also associated with a significant decrease in Prevotella in both the AMP and VAN groups. Taken together, these findings indicate that changes in gut microbiota as well as host physiology, including host metabolism and immunity, differ depending on the types of antibiotics, and the antibiotic-induced gut microbiota alteration has a correlation with host physiology such as host metabolic or immunological status. Thus, the immune and metabolic status of the host should be taken into account when administering antibiotics.