Prevotella Sp Research Articles

Gut Microbiome Changes among Undernutrition and Stunting Infants and Children under 2 Years: A Scoping Review

Background Undernutrition and stunting are significant public health concerns globally, particularly in low- and middle-income countries. Nutritional intervention is the cornerstone of the management and prevention of these conditions. However, the gut microbiome has recently emerged as an essential modulator of the effects of nutritional interventions in undernutrition and stunting. This scoping review aims to examine the impact of nutrition intake (including if there is any intervention) over time on gut microbiome changes in infants and children under the age of 2 who experience undernutrition and stunting. Methods A literature search was conducted in PubMed and Cochrane Library, including studies from 2013 to 2023, using terms related to malnutrition, stunting, failure to thrive, and gut microbiome. Inclusion criteria were applied to select eligible studies for review. Five studies were chosen to be included in this review. Results The findings indicate that nutrition intake over time, including dietary supplementation and prebiotics, can influence the gut microbiome composition, diversity, and functionality in undernutrition and stunting infants and children. These may promote the growth of beneficial bacteria while reducing the abundance of harmful pathogens. Moreover, improvements in nutritional status, growth parameters, and immune function were observed in association with positive changes in the gut microbiota. Conclusion Nutrition intake can positively modulate the gut microbiome in undernutrition and stunting infants by supporting the growth of beneficial gut bacteria such as Actinobacteria, Bacteroides, Streptococcus, Bifidobacterium, Prevotella sp, and other bacterial taxa that vary with age, ultimately contributing to enhanced growth and development outcomes. Further studies are needed to better understand the mechanisms underlying these effects and to develop targeted nutritional interventions that optimize the gut microbiome in undernutrition and stunting infants and children under 2 years.

Crystallization and Preliminary X-ray Diffraction Study of a Putative β-glycosidase from the Oral Bacteria Prevotella sp.

Crystallization and Preliminary X-ray Diffraction Study of a Putative β-glycosidase from the Oral Bacteria Prevotella sp.

The role of selenium intervention in gut microbiota homeostasis and gene function in mice with breast cancer on a high-fat diet.

This study aimed to investigate the effect of selenium on gut microbiota in mice with breast cancer under a high-fat diet. A total of 12 female BALB/c mice were randomly divided into two groups: 4 T1 + selenium+ high-fat diet group and 4 T1 + high-fat diet group. Mice were injected with 4 T1 cells on the right 4th mammary fat pad and kept on a high-fat diet. Fecal samples were collected, and DNA was extracted for metagenomic sequencing and bioinformatics analysis. Relevant target genes and pathways were annotated and metabolically analyzed to explore the intervention effect of selenium on breast cancer in the high-fat diet state. Selenium supplementation in the high-fat diet altered the composition and diversity of gut microbiota in mice with breast cancer. The gut microbial composition was significantly different in the selenium intervention group, with an increased abundance of Proteobacteria, Actinobacteria, and Verrucomicrobia phyla and species such as Helicobacter ganmani, Helicobacter japonicus, and Akkermansia muciniphila, while phyla, such as Bacteroidetes, Firmicutes, Deferribacteres, and Spirochaetes, and species, such as Prevotella sp. MGM2, Muribaculum intestinale, Lactobacillus murinus, and Prevotella sp. MGM1, were decreased. Functional analysis revealed differential expression of genes related to carbohydrate-active enzymes, pathogen-host interactions, cell communication, cell auto-induction, membrane transporters, and virulence factors. Furthermore, 37 COGs and 48 metabolites with rising metabolic potential in the selenium intervention group were predicted. Selenium alters the homeostasis of gut microbiota in mice with breast cancer on a high-fat diet, affecting their composition, abundance, and associated metabolism. These findings suggest that the mechanism involves interfering with gut microbiota homeostasis, leading to altered synthesis of tumor-associated proteins and fatty acids and inducing tumor cell apoptosis and pyroptosis.

Effect of feed supplementation with docosahexaenoic acid in regio- and enantiopure triacylglycerols on gut metabolome and microbiota in rats

Docosahexaenoic acid [22:6(n-3), DHA] plays an important role in human physiology including gut health. This research aimed to investigate the impact of positional distribution of DHA in dietary triacylglycerols (TAG) on gut metabolomic profile and microbiota. In the 4-week feeding trial, the Sprague-Dawley rats were fed on an n-3 deficient feed supplemented with TAG containing DHA at the sn-1, 2, or 3 position and palmitic acid at the remaining positions. Three groups receiving standard n-3 adequate feed, n-3 deficient feed, or n-3 deficient feed supplemented with tripalmitin were included as controls. The gut metabolome was studied using LC–MS-based non-targeted metabolomics, and microbiota profiles were investigated by 16S rRNA sequencing. Compared to the n-3 adequate diet, four-week feeding on the n-3 deficient diet affected the fecal pyrimidine metabolism, steroid biosynthesis, and arginine and proline metabolism. Feeding with DHA-containing TAGs, especially TAG with DHA at sn-3 position, increased the level of N5-Carboxy aminoimidazole ribonucleotide related to purine biosynthesis and dimethylbenzimidazole involved in vitamin B2 biosynthesis. N-3 deficient diet lowered the abundance of the genus Alistipes and the species Bacteroides massiliensis in the gut microbiota. Compared to the n-3 deficient groups, feeding with DHA-containing TAGs decreased the abundance of species Prevotella sp. CAG: 1031, and feeding with sn-2 DHA resulted in an increase in the abundance of Bacteroides fragilis and a decrease in the abundance of Faecalibacterium sp. CAP 74. This is the first study showing that dietary DHA from different positions of TAG may affect gut metabolites and microbiota differently.

Multi-omics reveal mechanisms of high enteral starch diet mediated colonic dysbiosis via microbiome-host interactions in young ruminant

BackgroundAlthough rumen development is crucial, hindgut undertakes a significant role in young ruminants’ physiological development. High-starch diet is usually used to accelerate rumen development for young ruminants, but always leading to the enteral starch overload and hindgut dysbiosis. However, the mechanism behind remains unclear. The combination of colonic transcriptome, colonic luminal metabolome, and metagenome together with histological analysis was conducted using a goat model, with the aim to identify the potential molecular mechanisms behind the disrupted hindgut homeostasis by overload starch in young ruminants.ResultCompared with low enteral starch diet (LES), high enteral starch diet (HES)-fed goats had significantly higher colonic pathology scores, and serum diamine oxidase activity, and meanwhile significantly decreased colonic mucosal Mucin-2 (MUC2) protein expression and fecal scores, evidencing the HES-triggered colonic systemic inflammation. The bacterial taxa Prevotella sp. P4-67, Prevotella sp. PINT, and Bacteroides sp. CAG:927, together with fungal taxa Fusarium vanettenii, Neocallimastix californiae, Fusarium sp. AF-8, Hypoxylon sp. EC38, and Fusarium pseudograminearum, and the involved microbial immune pathways including the “T cell receptor signaling pathway” were higher in the colon of HES goats. The integrated metagenome and host transcriptome analysis revealed that these taxa were associated with enhanced pathogenic ability, antigen processing and presentation, and stimulated T helper 2 cell (TH2)-mediated cytokine secretion functions in the colon of HES goats. Further luminal metabolomics analysis showed increased relative content of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), and decreased the relative content of hypoxanthine in colonic digesta of HES goats. These altered metabolites contributed to enhancing the expression of TH2-mediated inflammatory-related cytokine secretion including GATA Binding Protein 3 (GATA3), IL-5, and IL-13. Using the linear mixed effect model, the variation of MUC2 biosynthesis explained by the colonic bacteria, bacterial functions, fungi, fungal functions, and metabolites were 21.92, 20.76, 19.43, 12.08, and 44.22%, respectively. The variation of pathology scores explained by the colonic bacterial functions, fungal functions, and metabolites were 15.35, 17.61, and 57.06%.ConclusionsOur findings revealed that enteral starch overload can trigger interrupted hindgut host-microbiome homeostasis that led to impaired mucosal, destroyed colonic water absorption, and TH2-mediated inflammatory process. Except for the colonic metabolites mostly contribute to the impaired mucosa, the nonnegligible contribution from fungi deserves more future studies focused on the fungal functions in hindgut dysbiosis of young ruminants.256VYnm1kgM5kPxw6ZAn-oVideo

Identifying the oral microbiome of adolescents with and without dental fluorosis based on full-length 16S rRNA gene sequencing.

Dental fluorosis, resulting from long-term environmental exposure to fluoride, is prevalent among diverse populations worldwide. Severe fluorosis not only compromises the aesthetic appeal of teeth but also impairs their functionality. This study aims to investigate the oral microbiome in dental fluorosis and the health individuals of adolescents living in the endemic fluorosis area of Guizhou, China through full-length 16S rDNA sequencing. Fourty-six individuals meet the sampling criteria, and we divided these samples into the following groups: a healthy group (H = 23) and a dental fluorosis group (F = 23), and two subgroups of Miao ethnicity: a healthy Miao group (Hm = 13) and a dental fluorosis Miao group (Fm = 15). A total of 660,389 high-quality sequences were obtained, and 12,007 Amplicon Sequence Variants (ASVs) were identified, revealing significant variations in oral microbiome between Fm and Hm groups. The composition of oral microbiota was similar between the H and F groups. At the genus level, Pseudopropionibacterium and at the species level, Streptococcus oralis_subsp.dentisani_clade_058 were less abundant in group F than in group H (P < 0.05). Further analysis revealed that the abundance of Capnocytophaga gingivalis and Kingella denitrificans was significantly lower in Fm fluorosis patients than in the Hm group (P < 0.05). Based on the LEfSe analysis, the potential core biomarkers in the oral of Fm fluorosis patients were identified at different taxonomic levels, ranging from phylum to species. These include Gammaproteobacteria, Prevotella sp_HMT_304, Gemella sanguinis, and Gracilibacteria_(GN02). Network analysis revealed that the microbiota in the fluorosis group exhibited more complex interactions with each other than the healthy group. Notably, within the Hm group, the potential biomarkers Capnocytophaga gingivalis and Kingella denitrificans exhibited a positive correlation. Finally, we employed PICRUSt2 analysis to explore the abundance clustering of the top 30 functional units in each sample, and we found that the metabolic pathway compositions of the four groups were similar. In summary, our findings suggest that the microbial composition of plaque in Hm patients with dental fluorosis is significantly altered, and we identified the potential marker microorganisms that contribute to these changes.

Antidepressant effects of sulforaphane (SFN) and its derivatives SLL-III-9 and SLL-III-120 and their potential underlying mechanisms based on the microbiota-gut-brain axis.

Broccoli (Brassica oleracea L.) is a vegetable with numerous nutritional properties, with sulforaphane (SFN) being the most abundant and unique bioactive ingredient. SFN has anti-inflammatory, antioxidant, and anti-cancer activities. In this study, a series of SFN derivatives were synthesized and screened for improved antidepressant effects. Among these, the SFN derivatives SLL-III-9 and SLL-III-120 were the best candidates, and the potential antidepressant mechanism of SFN, SLL-III-9, and SLL-III-120 associated with their effects in a chronic unpredictable mild stress (CUMS) mouse model was explored based on the microbiota-gut-brain axis. All three compounds were able to relieve depression-like behaviors in CUMS mice and regulate the composition of the gut bacteria Firmicutes, Actinobacteria, Parabasalia, and Tenericutes at the phylum level and Bacteroidales bacterium, Lachnospiraceae bacterium A4, Muribaculum intestinale, Muribaculaceae bacterium, and Prevotella sp. MGM1 at the species level, possibly altering their function associated with the anti-inflammatory effect. Additionally, SFN and its derivatives upregulated the expression of the tight junction proteins ZO-1, occludin, and claudin and increased the concentration of IL-10, dopamine (DA), 5-hydroxytryptamine (5-HT) and the brain-derived neurotrophic factor (BDNF), while downregulating the expressions of proteins related to the NF-κB/NLRP3 pathway and reducing the concentration of TNF-α. Further in vitro studies revealed significant inhibition of the production of inflammatory factors IL-1β, IL-18, IL-6, and TNF-α in LPS-activated BV2 cells via the NF-κB/NLRP3 pathway when these cells were treated with SFN or its two derivatives. Taken together, the results suggested that SFN and its two derivatives, SLL-III-9 and SLL-III-120, could be considered potential compounds for the development of a promising and safe agent for combating depression.

Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome.

Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI-], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. The median (IQR) age of our cohort was 14 years (12-16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI-, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI- and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.

Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals.

Although gut microbiota alteration and related blood microbe profiles in human immunodeficiency virus (HIV)-infected individuals are associated with the disease progression, how abnormal blood microbe profiles influence the inflammation and immune restoration are not fully understood. To address these issues, this study enrolled 24 healthy controls (HCs) and 91 HIV-infected individuals, including 30 treatment-naïve individuals (TNs), 31 immunological non-responders (INRs), and 30 immunological responders (IRs); subsequently, we analyzed blood microbe profiles using metagenomic sequencing and Olink proteomics technology, and identify inflammation-related proteins in peripheral blood samples of these individuals. The results showed increased translocation of microbes in the blood of TNs. This translocation did not return to normal level in either IRs or INRs who received antiretroviral therapy. In addition, Porphyromonas gingivalis significantly increased in TNs, IRs, and INRs compared to HCs. P. gingivalis was inversely associated with CD4+ T-cell counts, CD4/CD8 ratio, latency-associated peptide transforming growth factor-β1, and tumor necrosis factor-related activation-induced cytokine (TRANCE) and positively associated with HIV reservoirs. Burkholderia multivorans and Bacillus thuringiensis significantly decreased in TNs, IRs, and INRs compared to HCs and were positively associated with CD4+ T-cell counts and the CD4/CD8 ratio and negatively associated with HIV reservoir size and pro-inflammatory factors. We identified several species of microbes that were associated with CD4+ T-cell restoration on antiretroviral therapy, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius were positively associated with HIV reservoir size and pro-inflammatory proteins. Another group of bacteria, B. multivorans, B. thuringiensis, Vibrio vulnificus, and Acinetobacter baumannii, which were negatively associated and pro-inflammatory proteins. In conclusion, different microbes within blood of HIV-infected individuals were found to be closely associated with persistent inflammation and immune restoration, suggesting the blood microbe profiles of HIV-infected individuals also influence disease progression. IMPORTANCE The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.

Metagenome of Gut Microbiota Provides a Novel Insight into the Pathogenicity of Balantioides coli in Weaned Piglets

Balantioides coli plays an important role in the diarrhea of weaned piglets, but its pathogenic potential and interaction with gut microbes remain unclear. To investigate the impact of B. coli colonization on the gut bacterial structure and function of weaned piglets, a metagenomic analysis based on shotgun sequencing was performed on fresh fecal samples collected from ten B. coli-colonized piglets and eight B. coli-free ones in this study. The results showed that decreasing diversity and shifted composition and function of the bacterial community were detected in the weaned piglets infected by B. coli. In contrast to the B. coli-negative group, the relative abundances of some members of the Firmicutes phylum including Clostridium, Ruminococcus species, and Intestinimonas butyriciproducens, which produce short-chain fatty acids, were significantly reduced in the B. coli-positive group. Notably, some species of the Prevotella genus (such as Prevotella sp. CAG:604 and Prevotella stercorea) were significantly increased in abundance in the B. coli-positive piglets. A functional analysis of the gut microbiota demonstrated that the differential gene sets for the metabolism of carbohydrates and amino acids were abundant in both groups, and the more enriched pathways in B. coli-infected piglets were associated with the sugar-specific phosphotransferase system (PTS) and the two-component regulatory system, as well as lipopolysaccharide (LPS) biosynthesis. Furthermore, several species of Prevotella were significantly positively correlated to the synthesis of lipid A, leading to the exporting of endotoxins and, thereby, inducing inflammation in the intestines of weaned piglets. Taken together, these findings revealed that colonization by B. coli was distinctly associated with the dysbiosis of gut bacterial structure and function in weaned piglets. Lower relative abundances of Clostridiaceae and Ruminococcaceae and higher abundances of Prevotella species were biomarkers of B. coli infection in weaned piglets.

Fecal microbiota transplantation combined with anti-PD-1 inhibitor for unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.

105 Background: The gut microbiome is emerging as a key regulator of the immune system during immunotherapy. However, the effect of modulating the gut microbiome in patients (pts) with cancer refractory to immunotherapy remains largely unknown. We aimed to evaluate whether the fecal microbiota transplantation (FMT) could help overcome resistance in pts with advanced solid cancer refractory to anti-PD-(L)1 inhibitors and identify specific commensal bacteria that contribute to the efficacy of FMT (NCT04264975). Methods: This is a prospective, single-arm clinical trial of FMT plus anti-PD-(L)1 inhibitor in pts with advanced solid cancer refractory to anti-PD-(L)1 inhibitors. The key eligibility criteria for donors included ongoing durable complete or partial response ≥ 6 months with anti-PD-(L)1 monotherapy for advanced solid tumors. FMT was performed using colonoscopy, followed by continuation or reintroduction of anti-PD-(L)1 inhibitor until unacceptable toxicity or disease progression. Repeated FMT from the same or different donors was allowed. Results: From Jan. 2019 to Aug. 2020, 13 pts with metastatic gastric cancer (GC) (n=4), esophageal squamous cell carcinoma (ESCC) (n=5), and hepatocellular carcinoma (HCC) (n=4) were enrolled; male (77%), median age=60 yrs (range, 38-76), and median line of prior systemic therapy=3 (range, 2-5). All had confirmed disease progression on nivolumab monotherapy with primary (46.2%) or secondary resistance (53.8%), and underwent FMT with continued nivolumab. There were six FMT donors (HCC [n=4], GC [n=1], ESCC) [n=1], who had maintained (CR; n=4) or (PR; n=2) with nivolumab or pembrolizumab monotherapy. Of the 13 recipients, five showed SD and one achieved PR after FMT with a disease control rate of 46.2% (6/13) and an objective response rate of 7.7% (1/13). Recipient #7 (R7), who had metastatic HCC with primary resistance to nivolumab, initially showed PD to the 1st FMT from donor #1, but achieved PR after the 2nd FMT from donor #5. Clinical response was accompanied by an increase in levels of cytotoxic T cells in the blood and tumor microenvironment, immune cytokines, and the relative abundance of a new species derived from donor #5 showing 97% whole genome nucleotide sequence similarity with Prevotella sp. Marseille-P4119. We isolated this species from feces of R7 and preclinical experiments showed that treatment with this species activated human CD4+ and CD8+ T cells with increased IFN-γ secretion, and suppressed tumor growth in a syngeneic mouse model by enhancing tumor infiltration of cytotoxic T cells. Moreover, the combination treatment with anti-PD-1 and this species reduced the tumor volume more than with anti-PD-1 alone. Conclusions: FMT containing the effective microbiota could overcome resistance to anti-PD-1 inhibitor by modulating the tumor microenvironment in advanced solid cancer pts. Clinical trial information: NCT04264975 .

Pursuing new periodontal pathogens with an improved RNA-oligonucleotide quantification technique (ROQT)

ObjectiveThe aim of this study was to optimize the sensitivity, specificity and cost-effectiveness of the RNA-Oligonucleotide Quantification Technique (ROQT) in order to identify periodontal pathogens that remain unrecognized or uncultured in the oral microbiome. DesignTotal nucleic acids (TNA) were extracted from subgingival biofilm samples using an automated process. RNA, DNA and Locked Nucleic Acid (LNA) digoxigenin-labeled oligonucleotide probes targeting 5 cultivated/named species and 16 uncultivated or unnamed bacterial taxa were synthesized. Probe specificity was determined by targeting 96 oral bacterial species; sensitivity was assessed using serial dilutions of reference bacterial strains. Different stringency temperatures were compared and new standards were tested. The tested conditions were evaluated analyzing samples from periodontally healthy individuals, and patients with moderate or severe periodontitis. ResultsThe automated extraction method at 63⁰C along with LNA-oligunucleotides probes, and use of reverse RNA sequences for standards yielded stronger signals without cross-reactions. In the pilot clinical study, the most commonly detected uncultivated/unrecognized species were Selenomonas sp. HMT 134, Prevotella sp. HMT 306, Desulfobulbus sp. HMT 041, Synergistetes sp. HMT 360 and Bacteroidetes HMT 274. In the cultivated segment of the microbiota, the most abundant taxa were T. forsythia HMT 613 and Fretibacterium fastidiosum (formerly Synergistetes) HMT 363. ConclusionsIn general, samples from severe patients had the greatest levels of organisms. Classic (T. forsythia, P. gingivalis) and newly proposed (F. alocis and Desulfobulbus sp. HMT 041) pathogens were present in greater amounts in samples from severe periodontitis sites, followed by moderate periodontitis sites.

Characterization of gut microbial and metabolite alterations in faeces of Goto Kakizaki rats using metagenomic and untargeted metabolomic approach.

In recent years, the incidence of type 2 diabetes (T2DM) has shown a rapid growth trend. Goto Kakizaki (GK) rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients. A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites. We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance. To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics. Ten GK rats (model group) and Wistar rats (control group) were observed for 10 wk, and various glucose-related indexes, mainly including weight, fasting blood glucose (FBG) and insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β cell (HOMA-β) were assessed. The faecal gut microbiota was sequenced by metagenomics, and faecal metabolites were analysed by untargeted metabolomics. Multiple metabolic pathways were evaluated based on the differential metabolites identified, and the correlations between blood glucose and the gut microbiota and metabolites were analysed. The model group displayed significant differences in weight, FBG and insulin levels, HOMA-IR and HOMA-β indexes (P < 0.05, P < 0.01) and a shift in the gut microbiota structure compared with the control group. The results demonstrated significantly decreased abundances of Prevotella sp. CAG:604 and Lactobacillus murinus (P < 0.05) and a significantly increased abundance of Allobaculum stercoricanis (P < 0.01) in the model group. A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus. An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups. Fourteen potential metabolic biomarkers, including glycochenodeoxycholic acid, uric acid, 13(S)-hydroxyoctadecadienoic acid (HODE), N-acetylaspartate, β-sitostenone, sphinganine, 4-pyridoxic acid, and linoleic acid, were identified. Moreover, FBG and HOMA-IR were found to be positively correlated with glutathione, 13(S)-HODE, uric acid, 4-pyridoxic acid and allantoic acid and ne-gatively correlated with 3-α, 7-α, chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane (P < 0.05, P < 0.01). Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine (P < 0.01), and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp. CAG:604 (P < 0.01). The metabolic pathways showing the largest differences were arginine biosynthesis; primary bile acid biosynthesis; purine metabolism; linoleic acid metabolism; alanine, aspartate and glutamate metabolism; and nitrogen metabolism. Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.

Association of gut microbiota and SCFAs with finishing weight of Diannan small ear pigs.

Finishing weight is a key economic trait in the domestic pig industry. Evidence has linked the gut microbiota and SCFAs to health and production performance in pigs. Nevertheless, for Diannan small ear (DSE) pigs, a specific pig breed in China, the potential effect of gut microbiota and SCFAs on their finishing weight remains unclear. Herein, based on the data of the 16S ribosomal RNA gene and metagenomic sequencing analysis, we found that 13 OTUs could be potential biomarkers and 19 microbial species were associated with finishing weight. Among these, carbohydrate-decomposing bacteria of the families Streptococcaceae, Lactobacillaceae, and Prevotellaceae were positively related to finishing weight, whereas the microbial taxa associated with intestinal inflammation and damage exhibited opposite effects. In addition, interactions of these microbial species were found to be linked with finishing weight for the first time. Gut microbial functional annotation analysis indicated that CAZymes, such as glucosidase and glucanase could significantly affect finishing weight, given their roles in increasing nutrient absorption efficiency. Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthologies (KOs) and KEGG pathways analysis indicated that glycolysis/gluconeogenesis, phosphotransferase system (PTS), secondary bile acid biosynthesis, ABC transporters, sulfur metabolism, and one carbon pool by folate could act as key factors in regulating finishing weight. Additionally, SCFA levels, especially acetate and butyrate, had pivotal impacts on finishing weight. Finishing weight-associated species Prevotella sp. RS2, Ruminococcus sp. AF31-14BH and Lactobacillus pontis showed positive associations with butyrate concentration, and Paraprevotella xylaniphila and Bacteroides sp. OF04-15BH were positively related to acetate level. Taken together, our study provides essential knowledge for manipulating gut microbiomes to improve finishing weight. The underlying mechanisms of how gut microbiome and SCFAs modulate pigs' finishing weight required further elucidation.

The effects of elemene emulsion injection on rat fecal microbiota and metabolites: Evidence from metagenomic exploration and liquid chromatography-mass spectrometry.

Elemene emulsion injection (EEI) has been approved for interventional and intracavitary chemotherapy in treating malignant ascites in China, but few studies have focused on the effects of EEI on gut microbiota and metabolites. In this study, we investigated the effects of EEI on the fecal microbiota and metabolites in healthy Sprague-Dawley (SD) rats. We randomly assigned 18 male SD rats to three groups (n = 6 in each group): the sham group (group S), the low-concentration EEI group (L-EEI), and the high-concentration EEI group (H-EEI). The L-EEI and H-EEI rats were administered 14 days of consecutive EEI, 20 mg/kg, and 40 mg/kg intraperitoneally (IP). Group S rats were administered the same volume of normal saline. On day 14, each animal's feces were collected for metagenomic sequencing and metabolomic analysis, and the colonic contents were collected for 16S rRNA sequencing. EEI could alter the β-diversity but not the α-diversity of the fecal microbiota and induce structural changes in the fecal microbiota. Different concentrations of EEI affect the fecal microbiota differently. The effects of different EEI concentrations on the top 20 bacteria with significant differences at the species level among the three groups were roughly divided into three categories: (1) A positive or negative correlation with the different EEI concentrations. The abundance of Ileibacterium Valens increased as the EEI concentration increased, while the abundance of Firmicutes bacteria and Clostridium sp. CAC: 273 decreased. (2) The microbiota showed a tendency to increase first, then decrease or decrease first, and then increase as EEI concentration increased-the abundance of Prevotella sp. PCHR, Escherichia coli, and Candidatus Amulumruptor caecigallinarius tended to decrease with L-EEI but significantly increased with H-EEI. In contrast, L-EEI significantly increased Ruminococcus bromii and Dorea sp. 5-2 abundance, and Oscillibacter sp. 1-3 abundance tended to increase, while H-EEI significantly decreased them. (3) L-EEI and H-EEI decreased the abundance of bacteria (Ruminococcaceae bacterium, Romboutsia ilealis, and Staphylococcus xylosus). Fecal metabolites, like microbiota, were sensitive to different EEI concentrations and correlated with fecal microbiota and potential biomarkers. This study shows that intraperitoneal EEI modulates the composition of rat fecal microbiota and metabolites, particularly the gut microbiota's sensitivity to different concentrations of EEI. The impact of changes in the microbiota on human health remains unknown, particularly EEI's efficacy in treating tumors.

Exploring a Possible Link between the Fecal Microbiota and the Production Performance of Pigs.

Simple SummaryThe aim of this study is to investigate the relationship between fecal microbiota and the backfat thickness of pigs by 16S rRNA gene sequencing. Our study found that there were significant differences in the composition of microbiota at the species level, characterized by a higher abundance of Lactobacillus reuteri (L. reuteri) in pigs with low-backfat thickness. Additionally, functional profiling of microbial communities indicated that the isoquinoline alkaloid biosynthesis, arachidonic acid metabolism, and styrene degradation were significantly different between low- and high-backfat thickness groups. Furthermore, feeding L. reuteri reduced the intake-to-gain ratio and had the potential to reduce backfat thickness. These findings show that microbiota could alter the production performance of pigs.The backfat thickness of pigs not only affects the physical properties and taste of meat, but it also closely relates to the reproduction performance of sows. Accumulating evidence indicates that, apart from genetic factors, gut microbiota can also modulate the fat deposition and muscle growth. However, the differential microbiota in pigs with different backfat thickness, and whether microbiota affects backfat thickness, remains elusive. Firstly, 16S ribosomal RNA (16S rRNA) gene sequencing was performed on 62 fecal samples from pigs with different backfat thicknesses, and the compositions of microbiota among different groups with different backfat thicknesses were different. The abundance of Lactobacillus. reuteri (L. reuteri) and Prevotella sp RS2 was significantly higher in pigs with low-backfat thickness than that in pigs with middle and high-backfat thickness; meanwhile, the abundance of Desulfovibrio piger was significantly lower (p < 0.05) in pigs with low-backfat thickness. Furthermore, the functional profiling of microbial communities suggested that the abundance of isoquinoline alkaloid biosynthesis and styrene degradation were significantly lower (p < 0.05) in the low-backfat thickness group than that in middle and high-backfat thickness groups. Finally, L. reuteri fed to Meishan piglets was capable of improving the production performance and had the potential to reduce backfat thickness. This study provides new evidence that microbiota can regulate the phenotype of the host, and dietary supplementation with L. reuteri can improve the production performance of piglets.

Riemerella anatipestifer AS87_RS02955 Acts as a Virulence Factor and Displays Endonuclease Activity.

Riemerella anatipestifer is an important bacterial pathogen in the global duck industry and causes heavy economic losses. In our previous study, we demonstrated that R. anatipestifer type IX secretion system components GldK and GldM, and the secretion protein metallophosphoesterase, acted as virulence factors. In this study, R. anatipestifer AS87_RS02955 was investigated for virulence and enzymatic activity properties. We constructed AS87_RS02955 mutation and complementation strains to assess bacterial virulence. In vivo bacterial loads showed a significantly reduced bacterial loads in the blood of ducks infected with mutant strain Yb2Δ02955, which was recovered in the blood of ducks infected with the complementation strain cYb2Δ02955, demonstrating that AS87_RS02955 was associated with virulence. Further studies showed AS87_RS02955 was a novel nonspecific endonuclease with no functionally conserved domain, but enzymatic activity toward DNA and RNA was indicated. DNase activity was activated by Zn2+, Cu2+, Mg2+, Ca2+, and Mn2+ ions but inhibited by ethylenediaminetetraacetic acid. RNase activity was independent of metal cations, but stimulated by Mg2+, Ca2+, and Mn2+. RAS87_RS02955 enzymatic activity was active across a broad pH and temperature range. Moreover, we identified four sites in rAS87_RS02955, F39, F92, I134, and F145, which were critical for enzymatic activity. In summary, we showed that R. anatipestifer AS87_RS02955 encoded a novel endonuclease with important roles in bacterial virulence. IMPORTANCE R. anatipestifer AS87_RS02955 was identified as a novel T9SS effector and displayed a nonspecific endonuclease activity in this study. The protein did not contain a conserved His-Asn-His motif structure, which is similar to the endonuclease from Prevotella sp. Its mutant strain Yb2Δ02955 demonstrated significantly attenuated virulence, suggesting AS87_RS02955 is an important virulence factor. Moreover, AS87_RS02955 displayed nonspecific endonuclease activity to cleave λ DNA and MS2 RNA, while four protein sites were critical for endonuclease activity. In conclusion, R. anatipestifer AS87_RS02955 plays important roles in bacterial virulence.

Characteristics of salivary microbiota in children with obstructive sleep apnea: A prospective study with polysomnography.

ObjectivesThe present study aimed to investigate the characteristics of salivary microbiota of children with obstructive sleep apnea (OSA) and to assess longitudinal alterations in salivary microbiota before and after adenotonsillectomy.MethodsA set of cross-sectional samples consisted of 36 OSA children (17 boys and 19 girls, 7.47 ± 2.24 years old) and 22 controls (9 boys and 13 girls, 7.55 ± 2.48 years old) were included in the study, among which eight OSA children (five boys and three girls, 8.8 ± 2.0 years old) who underwent treatment of adenotonsillectomy were followed up after 1 year. Saliva samples were collected, and microbial profiles were analyzed by bioinformatics analysis based on 16S rRNA sequencing.ResultsIn cross-sectional samples, the OSA group had higher α-diversity as estimated by Chao1, Shannon, Simpson, Pielou_e, and observed species as compared with the control group (p < 0.05). β-Diversity based on the Bray–Curtis dissimilarities (p = 0.004) and Jaccard distances (p = 0.001) revealed a significant separation between the OSA group and control group. Nested cross-validated random forest classifier identified the 10 most important genera (Lactobacillus, Escherichia, Bifidobacterium, Capnocytophaga, Bacteroidetes_[G-7], Parvimonas, Bacteroides, Klebsiella, Lautropia, and Prevotella) that could differentiate OSA children from controls with an area under the curve (AUC) of 0.94. Linear discriminant analysis effect size (LEfSe) analysis revealed a significantly higher abundance of genera such as Prevotella (p = 0.027), Actinomyces (p = 0.015), Bifidobacterium (p < 0.001), Escherichia (p < 0.001), and Lactobacillus (p < 0.001) in the OSA group, among which Prevotella was further corroborated in longitudinal samples. Prevotella sp_HMT_396 was found to be significantly enriched in the OSA group (p = 0.02) with significantly higher levels as OSA severity increased (p = 0.014), and it had a lower abundance in the post-treatment group (p = 0.003) with a decline in each OSA child 1 year after adenotonsillectomy.ConclusionsA significantly higher microbial diversity and a significant difference in microbial composition and abundance were identified in salivary microbiota of OSA children compared with controls. Meanwhile, some characteristic genera (Prevotella, Actinomyces, Lactobacillus, Escherichia, and Bifidobacterium) were found in OSA children, among which the relationship between Prevotella spp. and OSA is worth further studies.

Antibiotic resistance genes and bacterial community distribution patterns in pig farms.

Antibiotic-resistant pathogens pose high risks to human and animal health worldwide. In recent years, many studies have been carried out to investigate the role of gut microbiota as a pool of antibiotic resistance genes (ARGs) in human and animals. Both the structure and function of the gut bacterial community and related ARGs in pig remain unknown. In this study, we characterized the gut microbiomes and resistomes of fecal samples collected from sixteen pig farms located in sixteen cities of Shandong Province by metagenomic sequencing. Alpha diversity indicated that fecal samples from Dezhou (DZ) and Jinan (J) showed higher alpha diversity, and the lowest was from pig farms of Rizhao (RZ). Other pig farms showed similar alpha diversity. Besides, we found that the composition of gut bacterial among these pig farms varied greatly. Helcococcus massiliensis was the dominant bacterial species in pig farms of RZ and Zibo (ZB), while Prevotella sp. P5-92 occupied a superior proportion in Binzhou (BZ) and Yantai (YT). The proportion of Lactobacillus johnsonii was similar among farms of Qingdao (QD), Linyi (LY), Taian (TA), Weifang (WF), Weihai (WH), and YT. In total, 1112 ARGs were obtained and classified into 69 groups from 48 fecal samples. ARG abundance was higher in farms of Dongying (DY) and WH than others, while the lowest farms in BZ and ZB. Interestingly, it is found that BZ pig farm was exclusive, so the tetQ gene showed a higher abundance. In contrast, the load of APH(3') - IIIa in fecal samples from DY, J-1, LC, WF, and WH was high. Meanwhile, the most relevant ARGs and the corresponding microbes were screened out. Our metagenomic sequencing data provides new insights into the abundance, diversity, and structure of bacterial community in pig farms. Meanwhile, we screened ARG-carrying bacteria and explored the correlation between ARGs and bacterial community, which provide a comprehensive view of the pig fecial ARGs and microbes in different farms of Shandong.

Microbiome associations between esophageal adenocarcinoma and esophageal squamous cell carcinoma.

e16050 Background: Microbiomes in tumor environment are thought to be associated with outcomes of precision therapy. Esophageal squamous cell carcinoma (ESCC) and Eophageal adenocarcinoma (EA) are the two subtypes of esophageal cancer. Although gene mutation and expression profiles have been well characterized, the microbial set between them are poorly studied. Methods: The microbial dataset of the identified species and their relative abundance using whole genome sequencing (WGS) and whole exome sequencing (WES) was obtained from TCMA database, which includes 17 EA samples and 32 ESCC samples. To investigate the microbial difference between EA and ESCC, The alpha diversity (Shanno and Simpson index) and beta diversity (PCoA, NMDS, Adonis) were calculated using the identified species to examine the overall difference between the two subtypes. The student's t-test were used to examine the relative abundance of single species Using the identified differential abundant microbial species, correlation analysis were performed to investigate whether synergistic effects exist for some species between the two subtypes. Moreover, taxonomy set enrichment analysis was used to find out whether the differential genus between EA and ESCC were associated with cancers. Finally, cox regression was used to investigated differential species between EA and ESCC affected the survival rate of EA group or ESCC group. Results: Through alpha and beta diversities, we didn’t find overall difference between EA and ESCC both in WGS and WES datasets. However, seventeen and two differential abundance species were found using Student’s t-test in WGS and WES datasets, respectively. The relative abundances of the differential species were mostly higher in ESCC than in EA. Correlation analyses showed that prevotella sp. HMSC069G02 and prevotella sp. HMSC077E08 were highly correlated. There were eight differential species ( prevotella aurantiaca, prevotella dentalis, prevotella marshii, etc.) were found in WGS and two species ( prevotella sp. C561, prevotella pleuritidis) in WES, respectively. The ten species all belong to prevotella genus, and taxon set enrichment analysis showed prevotella genus was associated with esophageal cancer, implies the identified differential species may be different in ESCC and EA patients. Among them, prevotella dentalis and prevotella buccae were found to be potentially risk factors in ESCC after Cox regression. Conclusions: This study investigated the microbiome difference between EA and ESCC cancers. Although we didn’t find the overall difference between the two subtypes, our preliminary results showed there exist some differential species between two subtypes. We found prevotella dentalis and prevotella buccae were the potential risk factors in ESCC, and the results can help further understand the therapy outcome differences between EA and ESCC from the microbial aspect.