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Atopic dermatitis (AD) is a public health concern and is increasing in prevalence in urban areas. Recent advances in sequencing technology have demonstrated that the development of AD not only associate with the skin microbiome but gut microbiota. Gut microbiota plays an important role in allergic diseases including AD. The hypothesis of the “gut-skin” axis has been proposed and the cross-talk mechanism between them has been gradually demonstrated in the research. Probiotics contribute to the improvement of the intestinal environment, the balance of immune responses, regulation of metabolic activity. Most studies suggest that probiotic supplements may be an alternative for the prevention and treatment of AD. This study aimed to discuss the effects of probiotics on the clinical manifestation of AD based on gut microbial alterations. Here we reviewed the gut microbial alteration in patients with AD, the association between gut microbiota, epidermal barrier, and toll-like receptors, and the interaction of probiotics and gut microbiota. The potential mechanisms of probiotics on alleviating AD via upregulation of epidermal barrier and regulation of immune signaling had been discussed, and their possible effective substances on AD had been explored. This provides the supports for targeting gut microbiota to attenuate AD.

ABSTRACT Bacterial species in the human gut predominantly exist in the form of mixed-species biofilms on mucosal surfaces. In this study, the biofilm-forming ability of many human gut bacterial strains (133 strains recovered from human faeces) on mucin-coated and non-coated polystyrene surfaces was determined. A significant variation (P < 0.05) in the biofilm-forming ability of many bacterial species on both surfaces was noticed. Based on some preliminary trials, four bacterial species were selected (Bifidobacterium bifidum, Bifidobacterium longum subsp. infantis, Parabacteroides distasonis and Bacteroides ovatus), which could not form any abundant biofilm individually under the in vitro conditions investigated, but produced abundant biofilms when co-cultured in different combinations of two, three and four species, giving an evidence of synergistic interactions in multispecies biofilm formation. There was a 4.74-fold increase in the biofilm mass when all strains developed a biofilm together. Strain-specific qPCR analysis showed that B. bifidum was the most dominant species (56%) in the four-species biofilm after 24 h, followed by B. longum subsp. infantis (36.2%). Study involving cell free supernatant of the cooperating strains showed that cell viability as well as physical presence of cooperating cells were prerequisites for the observed synergy in biofilms. The molecular mechanism behind these interactions and subsequent effects on the functionality of the strains involved were not determined in our study but merit further work. Interactions among the bacteria dwelling in the human gut.

Bifidobacterium bifidum is part of the core microbiota of healthy infant guts where it may form biofilms on epithelial cells, mucosa, and food particles in the gut lumen. Little is known about transcriptional changes in B. bifidum engaged in synergistic multispecies biofilms with ecologically relevant species of the human gut. Recently, we reported prevalence of synergism in mixed-species biofilms formed by the human gut microbiota. This study represents a comparative gene expression analysis of B. bifidum when grown in a single-species biofilm and in two multispecies biofilm consortia with Bifidobacterium longum subsp. infantis, Bacteroides ovatus, and Parabacteroides distasonis in order to identify genes involved in this adaptive process in mixed biofilms and the influence on its metabolic and functional traits. Changes up to 58% and 43% in its genome were found when it grew in three- and four-species biofilm consortia, respectively. Upregulation of genes of B. bifidum involved in carbohydrate metabolism (particularly the galE gene), quorum sensing (luxS and pfs), and amino acid metabolism (especially branched chain amino acids) in both multispecies biofilms, compared to single-species biofilms, suggest that they may be contributing factors for the observed synergistic biofilm production when B. bifidum coexists with other species in a biofilm.

Akkermansia muciniphila is a commensal bacterium of the gut mucus layer. Although both in vitro and in vivo data have shown that A. muciniphila strains exhibit strain-specific modulation of gut functions, its ability to moderate immunity to ulcerative colitis have not been verified. We selected three isolated human A. muciniphila strains (FSDLZ39M14, FSDLZ36M5 and FSDLZ20M4) and the A. muciniphila type strain ATCC BAA-835 to examine the effects of different A. muciniphila strains on dextran sulfate sodium-induced colitis. All of the A. muciniphila strains were cultured anaerobically in brain heart infusion medium supplemented with 0.25% type II mucin from porcine stomach. To create animal models, colitis was established in C57BL/6 mice which randomly divided into six groups with 10 mice in each group by adding 3% dextran sulfate sodium to drinking water for 7 days. A. muciniphila strains were orally administered to the mice at a dose of 1 × 10 9 CFU. Only A. muciniphila FSDLZ36M5 exerted significant protection against ulcerative colitis (UC) by increasing the colon length, restoring body weight, decreasing gut permeability and promoting anti-inflammatory cytokine expression. However, the other strains (FSDLZ39M14, ATCC BAA-835 and FSDLZ20M4) failed to provide these effects. Notably, A. muciniphila FSDLZ20M4 showed a tendency to exacerbate inflammation according to several indicators. Gut microbiota sequencing showed that A. muciniphila FSDLZ36M5 supplementation recovered the gut microbiota of mice to a similar state to that of the control group. A comparative genomic analysis demonstrated that the positive effects of A. muciniphila FSDLZ36M5 compared with the FSDLZ20M4 strain may be associated with specific functional genes that are involved in immune defense mechanisms and protein synthesis. Our results verify the efficacy of A. muciniphila in improving UC and provide gene targets for the efficient and rapid screening of A. muciniphila strains with UC-alleviating effects.

Gut microbiome plays an essential role in asthma development, and probiotic-based manipulation of the gut microbiome has been proposed to prevent asthma. Although the preventive effect of Lactobacillus supplementation against allergies has been reported, the precise Lactobacillus species beneficial for effective prevention of asthma remain unidentified and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the efficacy of oral administration of six Lactobacillus species and the mechanism underlying asthma prevention via gut microbiome modulation. We investigated the effects of oral administration of L. rhamnosus, L. fermentum, L. casei, L. gasseri, L. salivarius, and L. reuteri (five strains of each species) on asthma and gut microbiome of house dust mite (HDM)-treated murine models of asthma. Of these, L. reuteri administration was the most effective: it alleviated airway inflammation, decreased total IgE and HDM-IgG1, and reduced Th2-associated pro-inflammatory cytokines. Moreover, modulation of specific microbial genera by L. reuteri was more effective in asthma prevention than the modulation of the overall microbiota composition. Lactobacillus and Enterococcus were enriched after L. reuteri supplementation and were closely associated with total IgE and IL-13 production. Furthermore, L. reuteri specifically altered the gut microbial function toward butyrate generation. Thus, L. reuteri may reduce the risk of asthma development by modulating specific gut microbiota to improve the lung immune environment. Our study suggests a novel option for gut microbiome manipulation via L. reuteri supplementation for suppression of asthma and other allergic diseases.

Background The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations and perform precisely targeted modulation for obese individuals. Results This study proposed a systematic machine learning framework and applied it to 870 human stool metagenomes across five countries to obtain comprehensive regional shared biomarkers and conduct a personalized modulation analysis. In our pipeline, a heterogeneous ensemble feature selection diagram is first developed to determine an optimal subset of biomarkers through the aggregation of multiple techniques. Subsequently, a deep reinforcement learning method was established to alter the targeted composition to the desired healthy target. In this manner, we can realize personalized modulation by counterfactual inference. Consequently, a total of 42 species were identified as regional shared biomarkers, and they showed good performance in distinguishing obese people from the healthy group (area under curve (AUC) =0.85) when demonstrated on validation datasets. In addition, by pooling all counterfactual explanations, we found that Akkermansia muciniphila , Faecalibacterium prausnitzii, Prevotella copri, Bacteroides dorei, Bacteroides eggerthii, Alistipes finegoldii, Alistipes shahii, Eubacterium sp. _CAG_180, and Roseburia hominis may be potential broad-spectrum targets with consistent modulation in the multi-regional obese population. Conclusions This article shows that based on our proposed machine-learning framework, we can obtain more comprehensive and accurate biomarkers and provide modulation analysis for the obese population. Moreover, our machine-learning framework will also be very useful for other researchers to further obtain biomarkers and perform counterfactual modulation analysis in different diseases.

Tryptophan is metabolized by microorganisms into various indole derivatives that have been proven to alleviate diseases and promote human health. Lactic acid bacteria (LAB) are a broad microbial concept, some of which have been developed as probiotics. However, the capacity of most LAB to metabolize tryptophan is unknown. In this study, the aim is to reveal the rule of tryptophan metabolism in LAB by multi-omics. The findings showed that LAB were rich in genes for tryptophan catabolism and that multiple genes were shared among LAB species. Although the number of their homologous sequences was different, they could still form the same metabolic enzyme system. The metabolomic analysis revealed that LAB were capable of producing a variety of metabolites. Strains belonging to the same species can produce the same metabolites and have similar yields. A few strains showed strain-specificity in the production of indole-3-lactic acid (ILA), indole-3-acetic acid, and 3-indolealdehyde (IAld). In the genotype-phenotype association analysis, the metabolites of LAB were found to be highly consistent with the outcomes of gene prediction, particularly ILA, indole-3-propionic acid, and indole-3-pyruvic acid. The overall prediction accuracy was more than 87% on average, which indicated the predictability of tryptophan metabolites of LAB. Additionally, genes influenced the concentration of metabolites. The levels of ILA and IAld were significantly correlated with the numbers of aromatic amino acid aminotransferase and amidase, respectively. The unique indolelactate dehydrogenase in Ligilactobacillus salivarius was the primary factor contributing to its large production of ILA. In summary, we demonstrated the gene distribution and production level of tryptophan metabolism in LAB and explored the correlation between genes and phenotypes. The predictability and specificity of the tryptophan metabolites in LAB were proven. These results provide a novel genomic method for the discovery of LAB with tryptophan metabolism potential and offer experimental data for probiotics that produce specific tryptophan metabolites.

Lactobacillus is the dominant genus during fruit and vegetable juices (FVFs) fermentation, which are the key factors for taste and flavor. This study was performed to investigate the effects of different Lactobacillus spp. on profile of volatile flavor compounds and nonvolatile taste compounds in FVFs fermentation. A total of 14 compounds were identified as discriminant flavor and taste markers for fermented FVFs via gas chromatography–mass spectrometry (GC‐MS)‐based multimarker profiling. The PCA score plot and PLS‐DA showed that different FVFs were divided into three distinct types, suggesting that the different species significantly affect the volatile and nonvolatile compounds profiles of FVFs. Lactobacillus casei and Lactobacillus rhamnosus (Type A FVFs) might make a greater contribution to the umami taste. Lactobacillus plantarum and Lactobacillus acidophilus (Type B FVFs) make a greater contribution to the sour taste. Lactobacillus fermentum may be an potential critical contributor to produce volatile compounds. We reveal that different Lactobacillus strains play different roles in modifying these compounds related to flavor and taste features. The main factors affecting the flavor formation of fermented fruits and vegetables were obtained. The results will be beneficial for fruit and vegetable processing to achieve better and certain quality characteristics.

The gut microbiota could affect human health and disease. Although disease-associated microbiota alteration has been extensively investigated in the Chinese population, a nationwide Chinese gut microbiota baseline is still lacking. Here we performed 16 S rRNA gene sequencing on fecal samples from 2678 healthy Chinese individuals, who belonged to eight ethnic groups and resided in 63 counties/cities of 28 provinces. We identified four enterotypes, three of which were enriched for Prevotella, Bacteroides, and Escherichia, respectively, whereas the fourth one had no dominant genus. By assessing the association between the gut microbiota and 20 variables belonging to six categories, geography, demography, diet, urbanization, lifestyle, and sampling month, we revealed that geography explained the largest microbiota variation, and clarified the distinct patterns in the associations with staple food type, ethnicity, and urban/rural residence. Specifically, the gut microbiota of Han Chinese and ethnic minority groups from the same sites was more alike than that of the same ethnic minority groups from different sites. Individuals consuming wheat as staple food were predicted to have more microbial genes involving in glucan 1,3-beta-glucosidase and S-adenosyl-l-methionine biosynthesis than those who consumed rice, based on functional prediction. Besides, an appreciable effect of urbanization on decreased intra-individual diversity, increased inter-individual diversity, and increased proportion of the Bacteroides enterotype was observed. Collectively, our study provided a nationwide gut microbiota baseline of the Chinese population and knowledge on important covariates, which are fundamental to translational microbiota research.

Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.