Can longer lifespan be associated with gut microbiota involvement in lipid metabolism?

Biological aging is linked to altered body composition and reduced neuroactive steroid hormones like dehydroepiandrosterone sulfate (DHEAS), which can stimulate the GABA signaling pathway via gut microbiota. Our study examined the association of gut microbiota with lifespan in mice through comprehensive analysis of its composition and functional involvement in cholesterol sulfate, a precursor of DHEAS, metabolism. We used 16S rRNA and metagenomic sequencing, followed by metabolic pathway prediction and TLC and MALDI-TOF cholesterol sulfate identification. Significant increases in bacteria such as Bacteroides, typical for long-lived and Odoribacter and Colidextribacter, specific for short-lived mice were detected. Furthermore, for males (Rikenella, Alloprevotella) and females (Lactobacillus, Bacteroides), specific bacterial groups emerged as predictors (AUC=1), highlighting sex-specific patterns. Long-lived mice showed a strong correlation of Bacteroides (0.918) with lipid and steroid hormone metabolism, while a negative correlation of GABAergic synapse with body weight (-0.589). We found that several Bacteroides species harboring the sulfotransferase gene and gene cluster for sulfonate donor synthesis are involved in converting cholesterol to cholesterol sulfate, significantly higher in the feces of long-lived individuals. Overall, we suggest that increased involvement of gut bacteria, mainly Bacteroides spp., in cholesterol sulfate synthesis could ameliorate aging through lipid metabolism.

Investigating the bacterial profiles of Lactobacillus, Bifidobacterium, Actinobacteria, Fusobacterium, Firmicutes, and Bacteroides in stool samples from patients with severe depression and healthy individuals.

Depression is a multifaceted mental health disorder with complex etiology and significant global burden. Recent research indicates that the gut microbiota plays a role in the pathophysiology of depression, highlighting the potential role of specific bacterial species in influencing mood and cognitive function. In this study, we aimed to investigate the presence, copy numbers, and Ct values of selected bacterial species in stool samples from depressed patients (n=50) compared to control subjects (n=50). Our findings revealed significant differences in the abundance of Fusobacterium spp., Bifidobacterium spp., Lactobacillus spp., Bacteroidetes phylum, Firmicutes phylum, and Actinobacteria spp. between the two groups. Dysregulation of the gut microbiota, characterized by decreased presence of beneficial bacteria (e.g., Bifidobacterium spp., Lactobacillus spp.) and altered abundance of potentially pathogenic bacteria (e.g., Fusobacterium spp.), may contribute to the development or exacerbation of depression. These findings support the emerging concept of the gut-brain axis and its role in mental health. However, further research is needed to better understand the underlying mechanisms and explore the therapeutic potential of microbiota-targeted interventions for depression. Understanding the intricate interplay between the gut microbiota and depression could pave the way for novel treatment strategies and personalized approaches in mental health care.

TolRad, a model for predicting radiation tolerance using Pfam annotations, identifies novel radiosensitive bacterial species from reference genomes and MAGs.

The trait of ionizing radiation (IR) tolerance is variable between bacterium, with species succumbing to acute doses as low as 60 Gy and extremophiles able to survive doses exceeding 10,000 Gy. While survival screens have identified multiple highly radioresistant bacteria, such systemic searches have not been conducted for IR-sensitive bacteria. The taxonomy-level diversity of IR sensitivity is poorly understood, as are genetic elements that influence IR sensitivity. Using the protein domain (Pfam) frequencies from 61 bacterial species with experimentally determined D10 values (the dose at which only 10% of the population survives), we trained TolRad, a random forest binary classifier, to distinguish between radiosensitive (D10 < 200 Gy) and radiation-tolerant (D10 > 200 Gy) bacteria. On untrained species, TolRad had an accuracy of 0.900. We applied TolRad to 152 UniProt-hosted bacterial proteomes associated with the human microbiome, including 37 strains from the ATCC Human Microbiome Collection, and classified 34 species as radiosensitive. Whereas IR-sensitive species (D10 < 200 Gy) in the training data set had been confined to the phylum Proteobacterium, this initial TolRad screen identified radiosensitive bacteria in two additional phyla. We experimentally validated the predicted radiosensitivity of a Bacteroidota species from the human microbiome. To demonstrate that TolRad can be applied to metagenome-assembled genomes (MAGs), we tested the accuracy of TolRad on Egg-NOG assembled proteomes (0.965) and partial proteomes. Finally, three collections of MAGs were screened using TolRad, identifying further phyla with radiosensitive species and suggesting that environmental conditions influence the abundance of radiosensitive bacteria. IMPORTANCE: Bacterial species have vast genetic diversity, allowing for life in extreme environments and the conduction of complex chemistry. The ability to harness the full potential of bacterial diversity is hampered by the lack of high-throughput experimental or bioinformatic methods for characterizing bacterial traits. Here, we present a computational model that uses de novo-generated genome annotations to classify a bacterium as tolerant of ionizing radiation (IR) or as radiosensitive. This model allows for rapid screening of bacterial communities for low-tolerance species that are of interest for both mechanistic studies into bacterial sensitivity to IR and biomarkers of IR exposure.

Regulation of Bacteroides acidifaciens by the aryl hydrocarbon receptor in IL-22-producing immune cells has sex-dependent consequential impact on colitis.

Introduction: Colitis is an inflammatory bowel disease (IBD) characterized by immune cell dysregulation and alterations in the gut microbiome. In our previous report, we showed a natural product in cruciferous vegetables and ligand of the aryl hydrocarbon receptor (AhR), indole-3-carbinol (I3C), was able to reduce colitis-induced disease severity and microbial dysbiosis in an interleukin-22 (IL-22) dependent manner. Methods: In the current study, we performed single-cell RNA sequencing (scRNAseq) from colonocytes during colitis induction and supplementation with I3C and show how this treatment alters expression of genes involved in IL-22 signaling. To further define the role of IL-22 signaling in I3C-mediated protection during colitis and disease-associated microbial dysbiosis, we generated mice with AhR deficiency in RAR-related orphan receptor c (Rorc)-expressing cells (AhR ΔRorc ) which depletes this receptor in immune cells involved in production of IL-22. Colitis was induced in wildtype (WT), AhR ΔRorc , and littermate (LM) mice with or without I3C treatment. Results: Results showed AhR ΔRorc mice lost the efficacy effects of I3C treatment which correlated with a loss of ability to increase IL-22 by innate lymphoid type 3 (ILC3s), not T helper 22 (Th22) cells. 16S rRNA microbiome profiling studies showed AhR ΔRorc mice were unable to regulate disease-associated increases in Bacteroides, which differed between males and females. Lastly, inoculation with a specific disease-associated Bacteroides species, Bacteroides acidifaciens (B. acidifaciens), was shown to exacerbate colitis in females, but not males. Discussion: Collectively, this report highlights the cell and sex-specific role of AhR in regulating microbes that can impact colitis disease.

Structural characterization and Bacteroides proliferation promotion activity of a novel homogeneous arabinoglucuronoxylan from Commelina communis L.

Commelina communis L., a functional food and herbal plant in Asia, has been used against obesity, diabetes, and infections for centuries. A growing body of studies has demonstrated that indigestible polysaccharides are significant in obesity management. However, the structures and bioactivities of homogeneous polysaccharides from C. communis remain unclear. This study presented the structural characterization, simulated digestion, and human gut Bacteroides proliferation promotion activity of a novel homogeneous polysaccharide (CCB-3) from C. communis. The results showed that CCB-3 was an arabinoglucuronoxylan, primarily composed of arabinose, galactose, xylose, glucuronic acid (GlcA), and 4-O-methyl GlcA with a molecular weight (Mw) of 58.8 kDa. Following a 6-hour exposure to simulated gastrointestinal fluid, the Mw of CCB-3 remained unchanged, revealing that CCB-3 was an indigestible polysaccharide. Notably, CCB-3 could promote the proliferation of B. thetaiotaomicron, B. ovatus, and B. cellulosilyticus and produce short-chain fatty acids (SCFAs) and 1,2-propanediol. These findings might shed light on the discovery of polysaccharide-based leading compounds from C. communis against obesity.

Extracellular vesicles from mesenchymal stem cells alter gut microbiota and improve neuroinflammation and motor impairment in rats with mild liver damage.

Gut microbiota perturbation and motor dysfunction have been reported in steatosis patients. Rats with mild liver damage (MLD) show motor dysfunction mediated by neuroinflammation and altered GABAergic neurotransmission in the cerebellum. The extracellular vesicles (EV) from mesenchymal stem cells (MSC) have emerged as a promising therapeutic proxy whose molecular basis relies partly upon TGFß action. This study aimed to assess if MSC-EVs improve motor dysfunction in rats with mild liver damage and analyze underlying mechanisms, including the role of TGFß, cerebellar neuroinflammation and gut microbiota. MLD in rats was induced by carbon tetrachloride administration and EVs from normal (C-EVs) or TGFß-siRNA treated MSCs (T-EV) were injected. Motor coordination, locomotor gait, neuroinflammation and TNF-α-activated pathways modulating GABAergic neurotransmission in the cerebellum, microbiota composition in feces and microbial-derived metabolites in plasma were analyzed. C-EVs reduced glial and TNFα-P2X4-BDNF-TrkB pathway activation restoring GABAergic neurotransmission in the cerebellum and improving motor coordination and all the altered gait parameters. T-EVs also improved motor coordination and some gait parameters, but the mechanisms involved differed from those of C-EVs. MLD rats showed increased content of some Bacteroides species in feces, correlating with decreased kynurenine aside from motor alterations. These alterations were all normalized by C-EVs, whereas T-EVs only restored kynurenine levels. Our results support the value of MSC-EVs on improving motor dysfunction in MLD and unveil a possible mechanism by which altered microbiota may contribute to neuroinflammation and motor impairment. Some of the underlying mechanisms are TGFß-dependent.

Impact of ginsenoside Rb1 on gut microbiome and associated changes in pharmacokinetics in rats.

Ginsenoside Rb1 exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb1. However, the impact of gut microbiota on the pharmacokinetics of Rb1 are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb1 intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb1 and Rd were substantially affected after orally supplementing Rb1 (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb1 and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb1 administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb1 pharmacokinetics.

Altered intestinal Streptococcus anginosus and 5α-reductase gene levels in patients with hepatocellular carcinoma and elevated Bacteroides stercoris in atezolizumab/bevacizumab non-responders.

Introduction. Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide.Gap statement. Monitoring of HCC and predicting its immunotherapy responses are challenging.Aim. This study explored the potential of the gut microbiome for HCC monitoring and predicting HCC immunotherapy responses.Methods. DNA samples were collected from the faeces of 22 patients with HCC treated with atezolizumab/bevacizumab (Atz/Bev) and 85 healthy controls. The gut microbiome was analysed using 16S rRNA next-generation sequencing and quantitative PCR (qPCR).Results. The microbiomes of patients with HCC demonstrated significant enrichment of Lactobacillus, particularly Lactobacillus fermentum, and Streptococcus, notably Streptococcus anginosus. Comparative analysis between Atz/Bev responders (R) and non-responders (NR) revealed a higher abundance of Bacteroides stercoris in the NR group and Bacteroides coprocola in the R group. Using qPCR analysis, we observed elevated levels of S. anginosus and reduced levels of 5α-reductase genes, essential for the synthesis of isoallolithocholic acid, in HCC patients compared to controls. Additionally, the analysis confirmed a significantly lower abundance of B. stercoris in the Atz/Bev R group relative to the NR group.Conclusions. The gut microbiome analysis and specific gene quantification via qPCR could provide a rapid, less invasive, and cost-effective approach for assessing the increased risk of HCC, monitoring patient status, and predicting immunotherapy responses.

Multi-omics approach for understanding the response of Bacteroides fragilis to carbapenems.

Background: The prevalence of Bacteroides fragilis isolates resistant to first-line beta-lactam drugs is increasing, resulting in reduced treatment efficacy. Investigating the bacterial transcriptome and proteome can uncover links between bacterial genes and resistance mechanisms. In this study, we experimentally assessed in vitro the transcriptional and proteomic profiles of B. fragilis exposed to SICs of meropenem, an effective antimicrobial agent, collected from patients with intra-abdominal diseases at Astana City Hospital, Kazakhstan. Methods: B. fragilis was cultured in brain heart infusion broth and sub-cultured every 48 h for 8 days in media with and without meropenem. Total RNA was extracted from the liquid cultures using a commercial RNeasy mini kit, and strand-specific RNA sequencing (RNA-seq) was performed on the DNBSEQ platform. Raw RNA-seq data were retrieved from BioProject No. PRJNA531645 and uploaded to the NCBI Sequence Read Archive (accession no. SRX22081155). Proteins of B. fragilis were extracted and separated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis, followed by analysis of the eluted peptides using liquid chromatography-tandem mass spectrometry. Cluster analysis utilised the Database for Annotation, Visualisation, and Integrated Discovery. Results: The subinhibitory concentration (SIC) of meropenem was determined to be 0.5 µg/L (minimum inhibitory concentration: 1). Mapping of reads to the reference genome identified 2477 expressed genes in all B. fragilis BFR KZ01 samples. Ten differentially expressed genes (DEGs) were common across comparison groups during and post-antibiotic exposure (wMEM vs. MEM2 and MEM2 vs. rMEM8); however, no substantially enriched Gene Ontology terms were identified. The cluster analysis highlighted a significant enrichment cluster (W-0560 oxidoreductase) of DEGs following antibiotic withdrawal. In total, 859 B. fragilis proteins were identified, with the expressions of three proteins, 3-oxoacyl-[acyl carrier protein] reductase, acetyl-CoA carboxylase biotin carboxylase subunit, and beta-ketoacyl-ACP synthase III, being upregulated in the enriched protein folding category. Notably, chaperone proteins such as FKBP-type peptidyl-prolyl cis-trans isomerases (involved in the cis-trans isomerisation of prolyl peptide bonds) and GroES (a co-chaperone functioning with GroEL) were also identified. Conclusions: Under the influence of low doses of antibiotics defense mechanisms are activated which contribute to the emergence of resistance. These results provide insight into the response of B. fragilis to meropenem exposure, mainly at the SIC, contributing to the understanding bacterial survival strategies under stress conditions.

Bacteroides salyersiae Is a Candidate Probiotic Species with Potential Anti-Colitis Properties in the Human Colon: First Evidence from an In Vivo Mouse Model.

Previous studies have indicated a critical role of intestinal bacteria in the pathogenesis of ulcerative colitis (UC). B. salyersiae is a commensal species from the human gut microbiota. However, what effect it has on UC development has not been investigated. In the present study, we explored this issue and demonstrated for the first time that oral administration of B. salyersiae CSP6, a bacterium previously isolated from the fecal sample of a healthy individual, protected against dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. In particular, B. salyersiae CSP6 improved mucosal damage and attenuated gut dysbiosis in the colon of DSS-fed mice. Specifically, B. salyersiae CSP6 decreased the population of pathogenic Escherichia-Shigella spp. and increased the abundance of probiotic Dubosiella spp. and Bifidobacterium pseudolongum. Additionally, by reshaping the colonic microbiota, B. salyersiae CSP6 remarkably increased the fecal concentrations of equol, 8-deoxylactucin, and tiglic acid, three beneficial metabolites that have been well documented to exert strong anti-inflammatory effects. Altogether, our study provides novel evidence that B. salyersiae is a candidate probiotic species with potential anti-colitis properties in the human colon, which has applications for the development of next-generation probiotics.

Determinants of raffinose family oligosaccharide use in Bacteroides species.

Bacteroides species are successful colonizers of the human colon and can utilize a wide variety of complex polysaccharides and oligosaccharides that are indigestible by the host. To do this, they use enzymes encoded in polysaccharide utilization loci (PULs). While recent work has uncovered the PULs required for the use of some polysaccharides, how Bacteroides utilize smaller oligosaccharides is less well studied. Raffinose family oligosaccharides (RFOs) are abundant in plants, especially legumes, and consist of variable units of galactose linked by α-1,6 bonds to a sucrose (glucose α-1-ß-2 fructose) moiety. Previous work showed that an α-galactosidase, BT1871, is required for RFO utilization in Bacteroides thetaiotaomicron. Here, we identify two different types of mutations that increase BT1871 mRNA levels and improve B. thetaiotaomicron growth on RFOs. First, a novel spontaneous duplication of BT1872 and BT1871 places these genes under the control of a ribosomal promoter, driving high BT1871 transcription. Second, nonsense mutations in a gene encoding the PUL24 anti-sigma factor likewise increase BT1871 transcription. We then show that hydrolases from PUL22 work together with BT1871 to break down the sucrose moiety of RFOs and determine that the master regulator of carbohydrate utilization (BT4338) plays a role in RFO utilization in B. thetaiotaomicron. Examining the genomes of other Bacteroides species, we found homologs of BT1871 in a subset and showed that representative strains of species with a BT1871 homolog grew better on melibiose than species that lack a BT1871 homolog. Altogether, our findings shed light on how an important gut commensal utilizes an abundant dietary oligosaccharide. IMPORTANCE: The gut microbiome is important in health and disease. The diverse and densely populated environment of the gut makes competition for resources fierce. Hence, it is important to study the strategies employed by microbes for resource usage. Raffinose family oligosaccharides are abundant in plants and are a major source of nutrition for the microbiota in the colon since they remain undigested by the host. Here, we study how the model commensal organism, Bacteroides thetaiotaomicron utilizes raffinose family oligosaccharides. This work highlights how an important member of the microbiota uses an abundant dietary resource.

Therapeutic Effects of Bacteroides fragilis Vesicles in a Model of Chemically Induced Colitis in Rats.

The anti-inflammatory properties of Bacteroides fragilis vesicles were studied in a rat model of dextran sodium sulfate-induced colitis. According to the histology results, addition of B. fragilis vesicles to the therapy promoted colon repair. Evaluation of the disease activity index confirms the high rate of colon recovery: against the background of vesicle administration, the absence of blood in stool, normal stool consistency, and body weight normalization were observed.

Evaluation of the Disk Diffusion Test for Bacteroides fragilis Group Clinical Isolates.

Background: Bacteroides fragilis group (BFG) isolates are the most frequently isolated gram-negative anaerobic bacteria and exhibit higher levels of antimicrobial resistance than other anaerobic bacteria. Reliable susceptibility testing is needed because of reports of resistance to the most active antibiotics. Recently, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) introduced disk zone diameter breakpoints. We evaluated the disk diffusion test (DDT) for susceptibility testing of BFG isolates compared with the agar dilution method. Methods: In total, 150 BFG isolates were collected from three institutes in Korea. The agar dilution method was conducted according to the CLSI guidelines. DDT was performed following the EUCAST guideline. Fastidious anaerobe agar supplemented with 5% defibrinated horse blood was used as the culture medium. Nine antimicrobials were evaluated: penicillin, cefoxitin, cefotetan, imipenem, meropenem, piperacillin-tazobactam, clindamycin, moxifloxacin, and metronidazole. Results: The categorical agreement (CA) between the two methods was >90.0% for imipenem, meropenem, clindamycin, and metronidazole. However, the CA for piperacillintazobactam was low, at 83.2%. Major errors were found: 5.4% for imipenem, 7.4% for meropenem, and 12.8% for piperacillin-tazobactam. All minor errors were <10%. We propose using the area of technical uncertainty (ATU) zone-overlapping area for susceptible and resistant strains to reduce errors in the DDT. Outside the ATU, the CAs of cefoxitin, cefotetan, and piperacillin-tazobactam were >90.0%, whereas that of moxifloxacin was increased to 88.5%. Conclusions: The DDT can be a useful alternative antimicrobial susceptibility test for BFG isolates when using the ATU zone to reduce errors.

Effect of BF839 + earthworm protein supplement on motor and some non-motor symptoms of Parkinson's disease: a randomized clinical trial.

Introduction: Some studies have found that probiotics have the potential to treat PD, and earthworm protein is a traditional Chinese medicine used for the treatment of PD. The purpose of this study was to evaluate the safety and efficacy of Bacteroides fragilis 839 (BF839) + earthworm protein supplement as an adjunctive therapy for PD and to observe changes in the gut microbiota. Methods: Forty-six patients with PD were recruited for a 12-week 1:1 randomized, double-blind, placebo-controlled clinical trial to evaluate changes in motor and some non-motor symptom scores and detect metagenomic changes in the gut microbiota. Results: From baseline to 12 weeks, compared with placebo, the trial group showed significant reductions in the United Parkinson's Disease Rate Scale (UPDRS) total score (-7.74 ± 5.92 vs. -1.83 ± 4.14, p < 0.001), UPDRS part I (-0.72 ± 0.81 vs. -0.20 ± 0.72, p = 0.026), UPDRS part II (-2.50 ± 2.24 vs. -0.22 ± 1.98, p = 0.001), UPDRS part III (-3.43 ± 3.42 vs. -1.33 ± 2.65, p = 0.024), and UPDRS part IV (-1.13 ± 1.19 vs. -0.15 ± 0.57, p = 0.001). Significant reductions in the Hamilton Depression Scale-24 score (-3.91 ± 3.99 vs. +1.15 ± 3.42, p < 0.001), Self-Rating Anxiety Scale scores (-7.04 ± 5.71 vs. -1.23 ± 2.34, p < 0.001), and Constipation scoring system scores (-8.59 ± 4.75 vs. 0.27 ± 1.24, p < 0.001), were also noted. In the trial group, one patient experienced mild eczema and one suffered low blood pressure, which could not be conclusively attributed to supplementation. Compared to the placebo group, the trial group showed a marked increase in Enterococcus faecium and a decrease in Klebsiella. Conclusion: This study is the first to report that probiotics plus earthworm protein can remarkably improve the motor and some non-motor symptoms of PD without serious adverse effects. However, further clinical trials and exploration of the underlying mechanisms are required. Clinical trial registration: Clinical trial registry http://www.chictr.org.cn/, Identification No: ChiCTR2000035122.

Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial.

Background: The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD. Methods: We examined 60 children aged 2-10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥106 CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16. Results: Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms. Conclusion: BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.

Causal Relationship of Skin Microbiota on Psoriasis: A Mendelian Randomization Study.

Objective: Epidemiological investigations have indicated an association between skin microbiota imbalance and psoriasis, however, the causal relationship has not been confirmed through Mendelian randomization (MR). MR employed genetic instrumental variables (IVs) to evaluate the causal relationship between skin microbiota and psoriasis, providing new insights for potential treatments. Methods: Summary statistics for psoriasis and related traits were available from FinnGen R10 and United Kingdom Biobank (UKB) consortium. The genome-wide association studies (GWAS) on skin microbiota in three skin microenvironments came from two population-based German cohorts. Several selection processes were used to determine the optimal instrumental variables. Five MR methods were performed and different sensitivity analyses approaches yield robustness evidence under different assumptions. Results: 449 SNPs were employed as IVs for 53 bacterial genera, with F-statistics between 20.18 and 42.44, indicating no evidence of weak instrument bias. Bacteroides was associated with psoriasis from UKB in IVW (OR, 95% CI: 0.914, 0.869-0.961; P < 0.001, PB-H = 0.007). The taxon was also associated with psoriasis vulgaris (IVW: OR, 95% CI, 0.918, 0.872-0.967; P = 0.001, P B-H = 0.054) and psoriasis and related disorders (IVW: OR, 95% CI, 0.915, 0.875-0.957; P < 0.001, P B-H = 0.008). Consistent causal estimates were identified in terms of both magnitude and direction, indicating a protective effect of Bacteroides. Conclusion: The MR study found that Bacteroides in the antecubital fossa may protect against psoriasis, offering genetic proof that skin microbiota helps prevent the condition.

Bacteroides uniformis degrades ß-glucan to promote Lactobacillus johnsonii improving indole-3-lactic acid levels in alleviating colitis.

BACKGROUND: Intake of dietary fiber is associated with a reduced risk of inflammatory bowel disease. ß-Glucan (BG), a bioactive dietary fiber, has potential health-promoting effects on intestinal functions; however, the underlying mechanism remains unclear. Here, we explore the role of BG in ameliorating colitis by modulating key bacteria and metabolites, confirmed by multiple validation experiments and loss-of-function studies, and reveal a novel bacterial cross-feeding interaction. RESULTS: BG intervention ameliorates colitis and reverses Lactobacillus reduction in colitic mice, and Lactobacillus abundance was significantly negatively correlated with the severity of colitis. It was confirmed by further studies that Lactobacillus johnsonii was the most significantly enriched Lactobacillus spp. Multi-omics analysis revealed that L. johnsonii produced abundant indole-3-lactic acid (ILA) leading to the activation of aryl hydrocarbon receptor (AhR) responsible for the mitigation of colitis. Interestingly, L. johnsonii cannot utilize BG but requires a cross-feeding with Bacteroides uniformis, which degrades BG and produces nicotinamide (NAM) to promote the growth of L. johnsonii. A proof-of-concept study confirmed that BG increases L. johnsonii and B. uniformis abundance and ILA levels in healthy individuals. CONCLUSIONS: These findings demonstrate the mechanism by which BG ameliorates colitis via L. johnsonii-ILA-AhR axis and reveal the important cross-feeding interaction between L. johnsonii and B. uniformis. Video Abstract.

Molecular characterization and antibiotic resistance of clinical Bacteroides and related genera from a tertiary care center in Türkiye.

OBJECTIVES: This study was conducted to measure the prevalence of antibiotic resistance, and corresponding resistance genes among Bacteroides and related genera in a tertiary hospital. METHODS: We examined 138 clinical strains of Bacteroides, Phocaeicola and Parabacteroides species isolated between July 2018 and June 2022. Antibiotic susceptibility tests were conducted using agar dilution. The bft gene and antibiotic resistance genes were targeted by real-time PCR. RESULTS: Resistance rates of all strains against ampicillin, cefoxitin, piperacillin-tazobactam, meropenem, imipenem, clindamycin, metronidazole, and tigecycline were 97.8 %, 28.3 %, 11.6 %, 7.9 %, 5.1 %, 47.8 %, 0 % and 4.3 %, respectively. Non-fragilis Bacteroidales spp. (NFB) exhibited lower susceptibility rates compared to B. fragilis for cefoxitin, clindamycin, and piperacillin-tazobactam. The prevalence of meropenem resistance was higher in B. fragilis (15.5 %) than in NFB (0 %). Among all strains, the rates of cepA, cfxA, cfiA, ermF, ermG, ermB, nim, linA, mefA, msrSA, tetQ, tetX, tetX1 and bft genes were 42.8 %, 44.9 %, 8.7 %, 44.2 %, 10.9 %, 2.2 %, 0.7 %, 29.0 %, 17.4 %, 7.2 %, 76.1 %, 8.0 %, 37.7 % and 16.7 %, respectively. In five B. fragilis strains, insertion sequences [IS1187(n = 3), ISBf6(n = 1), IS612B(n = 1)] were detected in the upstream region of cfiA. NimE with ISBf6 on plasmid pBFM29b was detected in one B. fragilis strain, intermediate to metronidazole (MIC = 16 µg/mL). ErmF was the most abundant gene responsible for clindamycin resistance. TetQ and tetX1 genes exhibited a higher frequency in strains that were not susceptible to tigecycline (MIC ≥8 µg/ml). CONCLUSIONS: Monitoring the resistance trends of Bacteroides and related genera is crucial given the observed resistance to all classes of antibiotics and the presence of various resistance mechanisms.

Bacteroides uniformis Ameliorates Carbohydrate and Lipid Metabolism Disorders in Diabetic Mice by Regulating Bile Acid Metabolism via the Gut-Liver Axis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. METHODS: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). RESULTS: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product-vaccarin (VAC)-that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. CONCLUSIONS: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.