[Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis].

Objective: To investigate the causality between intestinal flora and hypertrophic scars (HS) of human. Methods: This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora (n=18 473) and HS (n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results: A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions: There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

Gut microbiome composition reveals the distinctiveness between the Bengali people and the Indigenous ethnicities in Bangladesh.

Ethnicity has a significant role in shaping the composition of the gut microbiome, which has implications in human physiology. This study intends to investigate the gut microbiome of Bengali people as well as several indigenous ethnicities (Chakma, Marma, Khyang, and Tripura) residing in the Chittagong Hill Tracts areas of Bangladesh. Following fecal sample collection from each population, part of the bacterial 16 s rRNA gene was amplified and sequenced using Illumina NovaSeq platform. Our findings indicated that Bangladeshi gut microbiota have a distinct diversity profile when compared to other countries. We also found out that Bangladeshi indigenous communities had a higher Firmicutes to Bacteroidetes ratio than the Bengali population. The investigation revealed an unclassified bacterium that was differentially abundant in Bengali samples while the genus Alistipes was found to be prevalent in Chakma samples. Further research on these bacteria might help understand diseases associated with these populations. Also, the current small sample-sized pilot study hindered the comprehensive understanding of the gut microbial diversity of the Bangladeshi population and its potential health implications. However, our study will help establish a basic understanding of the gut microbiome of the Bangladeshi population.

Jian Gan powder ameliorates immunological liver injury in mice by modulating the gut microbiota and metabolic profiles.

BACKGROUND: Immunological liver injury (ILI) is a common liver disease associated with the microbiota-gut-liver axis. Jian Gan powder (JGP) exhibits both protective and therapeutic effects on hepatitis virus-induced ILI in the clinic. However, the underlying mechanisms remain elusive. The aim of this study is to investigate the hepatoprotective effects and associated mechanisms of JGP in the context of gut microbiota, utilizing a mouse model of ILI. METHODS: The mouse model was established employing Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS). Following treatment with JGP (7.5, 15, or 30 g/kg), serum, liver, and fresh fecal samples were analyzed. 16S rRNA gene sequencing and untargeted metabolomics profiling were performed to assess the role of JGP on the gut microbiota and its metabolites. RESULTS: JGP treatment markedly reduced serum IFN-γ, IL-6, IL-22, and hepatic p-STAT3 (phosphorylated transducer and activator of transcription-3) expression. In contrast, JGP increased the percentage of proliferating cell nuclear antigen-positive liver cells in treated mice. Fecal 16S rRNA gene sequencing revealed that JGP treatment restored the levels of Alloprevotella, Burkholderia-Caballeronia-Paraburkholderia, Muribaculum, Streptococcus, and Stenotrophomonas. Additionally, metabolomics analysis of fecal samples showed that JGP restored the levels of allylestrenol, eplerenone, phosphatidylethanolamine (PE) (P-20:0/0:0), sphingomyelin (SM) d27:1, soyasapogenol C, chrysin, and soyasaponin I. CONCLUSIONS: JGP intervention improves ILI by restoring gut microbiota and modifying its metabolic profiles. These results provide a novel insight into the mechanism of JGP in treating ILI and the scientific basis to support its clinical application.

Altered microbiome of serum exosomes in patients with acute and chronic cholecystitis.

BACKGROUND: This study aimed to investigate the differences in the microbiota composition of serum exosomes from patients with acute and chronic cholecystitis. METHOD: Exosomes were isolated from the serum of cholecystitis patients through centrifugation and identified and characterized using transmission electron microscopy and nano-flow cytometry. Microbiota analysis was performed using 16S rRNA sequencing. RESULTS: Compared to patients with chronic cholecystitis, those with acute cholecystitis exhibited lower richness and diversity. Beta diversity analysis revealed significant differences in the microbiota composition between patients with acute and chronic cholecystitis. The relative abundance of Proteobacteria was significantly higher in exosomes from patients with acute cholecystitis, whereas Actinobacteria, Bacteroidetes, and Firmicutes were significantly more abundant in exosomes from patients with chronic cholecystitis. Furthermore, functional predictions of microbial communities using Tax4Fun analysis revealed significant differences in metabolic pathways such as amino acid metabolism, carbohydrate metabolism, and membrane transport between the two patient groups. CONCLUSIONS: This study confirmed the differences in the microbiota composition within serum exosomes of patients with acute and chronic cholecystitis. Serum exosomes could serve as diagnostic indicators for distinguishing acute and chronic cholecystitis.

Association between gut microbiota and onset of type 2 diabetes mellitus: a two-sample Mendelian randomization study.

Aim: Mendelian randomization (MR) analysis has been used in the exploration of the role of gut microbiota (GM) in type 2 diabetes mellitus (T2DM); however, it was limited to the genus level. This study herein aims to investigate the relationship of GM, especially at the species level, with T2DM in order to provide some evidence for further exploration of more specific GM taxa and pathway abundance in T2DM. Methods: This two-sample MR study was based on the summary statistics of GM from the available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium as well as the Dutch Microbiome Project (DMP), whereas the summary statistics of T2DM were obtained from the FinnGen consortium released data. Inverse variance weighted (IVW), MR-Egger, strength test (F), and weighted median methods were used to examine the causal association between GM and the onset of T2DM. Cochran's Q statistics was employed to quantify the heterogeneity of instrumental variables. Bonferroni's correction was conducted to correct the bias of multiple testing. We also performed reverse causality analysis. Results: The corrected IVW estimates suggested the increased relative abundance of family Oxalobacteraceae (OR = 1.0704) and genus Oxalobacter (OR = 1.0874), respectively, were associated with higher odds of T2DM, while that of species faecis (OR = 0.9460) had a negative relationship with T2DM. The relationships of class Betaproteobacteria, family Lactobacillaceae, species finegoldii, and species longum with T2DM were also significant according to the IVW results (all P < 0.05). Conclusions: GM had a potential causal association with T2DM, especially species faecis, finegoldii, and longum. Further studies are still needed to clarify certain results that are contradictory with previous findings.

Causal associations between human gut microbiota and osteomyelitis: a Mendelian randomization study.

Background: Recent studies have emphasized the role of gut microbiota in the onset and progression of osteomyelitis. However, the exact types of gut microbiota and their mechanisms of action remain unclear. Additionally, there is a lack of theoretical support for treatments that improve osteomyelitis by altering the gut microbiota. Methods: In our study, we utilized the largest genome-wide association study (GWAS) meta-analysis to date from the MiBioGen consortium, involving 13,400 participants. The GWAS data for osteomyelitis were sourced from the UK Biobank, which included 4,836 osteomyelitis cases and 486,484 controls. We employed a two-sample Mendelian randomization framework for a detailed investigation into the causal relationship between gut microbiota and osteomyelitis. Our methods included inverse variance weighting, MR-Egger, weighted median, and weighted mode approaches. Additionally, we applied Cochran's Q statistic to assess the heterogeneity of the instrumental variable. Results: At the class level, Bacilli and Bacteroidia were positively correlated with the risk of osteomyelitis. At the order level, only Bacteroidales showed a positive association with osteomyelitis. At the genus level, an increased abundance of Butyricimonas, Coprococcus3, and Tyzzerella3 was positively associated with the risk of osteomyelitis, whereas Lachnospira was negatively associated. Sensitivity analyses showed no evidence of heterogeneity or pleiotropy. Conclusion: This study reveals that classes Bacilli and Bacteroidia, order Bacteroidales, and genera Butyricimonas, Coprococcus3, and Tyzzerella3 are implicated in increasing the risk of osteomyelitis, while the genus Lachnospira is associated with a reduced risk. Future investigations are warranted to elucidate the precise mechanisms through which these specific bacterial groups influence the pathophysiology of osteomyelitis.

Oral-to-rectum microbial transmission in orthopedic patients without a history of intestinal disorders.

The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%-9.37% of the rectal microbiota. Particularly, Streptococcus salivarius, Fusobacterium nucleatum, and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis, formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota.

Non-significant influence between aerobic and anaerobic sample transport materials on gut (fecal) microbiota in healthy and fat-metabolic disorder Thai adults.

Background: The appropriate sample handling for human fecal microbiota studies is essential to prevent changes in bacterial composition and quantities that could lead to misinterpretation of the data. Methods: This study firstly identified the potential effect of aerobic and anaerobic fecal sample collection and transport materials on microbiota and quantitative microbiota in healthy and fat-metabolic disorder Thai adults aged 23-43 years. We employed metagenomics followed by 16S rRNA gene sequencing and 16S rRNA gene qPCR, to analyze taxonomic composition, alpha diversity, beta diversity, bacterial quantification, Pearson's correlation with clinical factors for fat-metabolic disorder, and the microbial community and species potential metabolic functions. Results: Our study successfully obtained microbiota results in percent and quantitative compositions. Each sample exhibited quality sequences with a >99% Good's coverage index, and a relatively plateau rarefaction curve. Alpha diversity indices showed no statistical difference in percent and quantitative microbiota OTU richness and evenness, between aerobic and anaerobic sample transport materials. Obligate and facultative anaerobic species were analyzed and no statistical difference was observed. Supportively, the beta diversity analysis by non-metric multidimensional scale (NMDS) constructed using various beta diversity coefficients showed resembling microbiota community structures between aerobic and anaerobic sample transport groups (P = 0.86). On the other hand, the beta diversity could distinguish microbiota community structures between healthy and fat-metabolic disorder groups (P = 0.02), along with Pearson's correlated clinical parameters (i.e., age, liver stiffness, GGT, BMI, and TC), the significantly associated bacterial species and their microbial metabolic functions. For example, genera such as Ruminococcus and Bifidobacterium in healthy human gut provide functions in metabolisms of cofactors and vitamins, biosynthesis of secondary metabolites against gut pathogens, energy metabolisms, digestive system, and carbohydrate metabolism. These microbial functional characteristics were also predicted as healthy individual biomarkers by LEfSe scores. In conclusion, this study demonstrated that aerobic sample collection and transport (<48 h) did not statistically affect the microbiota and quantitative microbiota analyses in alpha and beta diversity measurements. The study also showed that the short-term aerobic sample collection and transport still allowed fecal microbiota differentiation between healthy and fat-metabolic disorder subjects, similar to anaerobic sample collection and transport. The core microbiota were analyzed, and the findings were consistent. Moreover, the microbiota-related metabolic potentials and bacterial species biomarkers in healthy and fat-metabolic disorder were suggested with statistical bioinformatics (i.e., Bacteroides plebeius).

The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis.

Background: Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore the causal relationship between gut microbiota and BTC, conduct an appraisal of the gut microbiome's utility in facilitating the early diagnosis of BTC. Methods: We acquired the summary data for Genome-wide Association Studies (GWAS) pertaining to BTC (418 cases and 159,201 controls) from the Biobank Japan (BBJ) database. Additionally, the GWAS summary data relevant to gut microbiota (N = 18,340) were sourced from the MiBioGen consortium. The primary methodology employed for the analysis consisted of Inverse Variance Weighting (IVW). Evaluations for sensitivity were carried out through the utilization of multiple statistical techniques, encompassing Cochrane's Q test, the MR-Egger intercept evaluation, the global test of MR-PRESSO, and a leave-one-out methodological analysis. Ultimately, a reverse Mendelian Randomization analysis was conducted to assess the potential for reciprocal causality. Results: The outcomes derived from IVW substantiated that the presence of Family Streptococcaceae (OR = 0.44, P = 0.034), Family Veillonellaceae (OR = 0.46, P = 0.018), and Genus Dorea (OR = 0.29, P = 0.041) exerted a protective influence against BTC. Conversely, Class Lentisphaeria (OR = 2.21, P = 0.017), Genus Lachnospiraceae FCS020 Group (OR = 2.30, P = 0.013), and Order Victivallales (OR = 2.21, P = 0.017) were associated with an adverse impact. To assess any reverse causal effect, we used BTC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between BTC and five different types of gut microbiota. The sensitivity analysis disclosed an absence of empirical indicators for either heterogeneity or pleiotropy. Conclusion: This investigation represents the inaugural identification of indicative data supporting either beneficial or detrimental causal relationships between gut microbiota and the risk of BTC, as determined through the utilization of MR methodologies. These outcomes could hold significance for the formulation of individualized therapeutic strategies aimed at BTC prevention and survival enhancement.

Similarities and differences: species and diet impact gut microbiota of captive pheasants.

The fecal microbiota plays an important role in maintaining animal health and is closely related to host life activities. In recent years, there have been an increasing number of studies on the fecal microbiota from birds. An exploration of the effects of species and living environments on the composition of gut microbiota will provide better protection for wildlife. In this study, non-injury sampling and 16S rDNA high-throughput sequencing were used to investigate the bacterial composition and diversity of the fecal microbiota in silver pheasants (Lophura nycthemera) and golden pheasants (Chrysolophus pictus) from Tianjin Zoo and Beijing Wildlife Park. The results showed that the abundance of Firmicutes was the highest in all fecal samples. At the genus level, Bacteroides was the common dominant bacteria, while there were some differences in other dominant bacteria genera. There were significant differences in fecal microbial composition between the golden pheasants from Tianjin Zoo and Beijing Wildlife Park. The metabolic analysis and functional prediction suggested that the gut microbiota composition and host metabolism were influenced by dietary interventions and living conditions. The results of this study provide the basis for further research of intestinal microbial of L. nycthemera and C. pictus, and valuable insights for conservation of related species.

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research.

Background: Gut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases. Methods: Thirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates. Results: The combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10-3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10-3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10-2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10-2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10-3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity. Conclusion: This study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.

Intestinal microbiome profiles in broiler chickens raised without antibiotics exhibit altered microbiome dynamics relative to conventionally raised chickens.

The present study was undertaken to profile and compare the cecal microbial communities in conventionally (CONV) grown and raised without antibiotics (RWA) broiler chickens. Three hundred chickens were collected from five CONV and five RWA chicken farms on days 10, 24, and 35 of age. Microbial genomic DNA was extracted from cecal contents, and the V4-V5 hypervariable regions of the 16S rRNA gene were amplified and sequenced. Analysis of 16S rRNA sequence data indicated significant differences in the cecal microbial diversity and composition between CONV and RWA chickens on days 10, 24, and 35 days of age. On days 10 and 24, CONV chickens had higher richness and diversity of the cecal microbiome relative to RWA chickens. However, on day 35, this pattern reversed such that RWA chickens had higher richness and diversity of the cecal microbiome than the CONV groups. On days 10 and 24, the microbiomes of both CONV and RWA chickens were dominated by members of the phylum Firmicutes. On day 35, while Firmicutes remained dominant in the RWA chickens, the microbiome of CONV chickens exhibited am abundance of Bacteroidetes. The cecal microbiome of CONV chickens was enriched with the genus Faecalibacterium, Pseudoflavonifractor, unclassified Clostridium_IV, Bacteroides, Alistipes, and Butyricimonas, whereas the cecal microbiome of RWA chickens was enriched with genus Anaerofilum, Butyricicoccu, Clostridium_XlVb and unclassified Lachnospiraceae. Overall, the cecal microbiome richness, diversity, and composition were greatly influenced by the management program applied in these farms. These findings provide a foundation for further research on tailoring feed formulation or developing a consortium to modify the gut microbiome composition of RWA chickens.

Impact of Limosilactobacillus fermentum probiotic treatment on gut microbiota composition in sahiwal calves with rotavirus diarrhea: A 16S metagenomic analysis study".

BACKGROUND: Diarrhea poses a major threat to bovine calves leading to mortality and economic losses. Among the causes of calf diarrhea, bovine rotavirus is a major etiological agent and may result in dysbiosis of gut microbiota. The current study was designed to investigate the effect of probiotic Limosilactobacillus fermentum (Accession No.OR504458) on the microbial composition of rotavirus-infected calves using 16S metagenomic analysis technique. Screening of rotavirus infection in calves below one month of age was done through clinical signs and Reverse Transcriptase PCR. The healthy calves (n = 10) were taken as control while the infected calves (n = 10) before treatment was designated as diarrheal group were treated with Probiotic for 5 days. All the calves were screened for the presence of rotavirus infection on each day and fecal scoring was done to assess the fecal consistency. Infected calves after treatment were designated as recovered group. Fecal samples from healthy, recovered and diarrheal (infected calves before sampling) were processed for DNA extraction while four samples from each group were processed for 16S metagenomic analysis using Illumina sequencing technique and analyzed via QIIME 2. RESULTS: The results show that Firmicutes were more abundant in the healthy and recovered group than in the diarrheal group. At the same time Proteobacteria was higher in abundance in the diarrheal group. Order Oscillospirales dominated healthy and recovered calves and Enterobacterials dominated the diarrheal group. Alpha diversity indices show that diversity indices based on richness were higher in the healthy group and lower in the diarrheal group while a mixed pattern of clustering between diarrheal and recovered groups samples in PCA plots based on beta diversity indices was observed. CONCLUSION: It is concluded that probiotic Limosilactobacillus Fermentum N-30 ameliorate the dysbiosis caused by rotavirus diarrhea and may be used to prevent diarrhea in pre-weaned calves after further exploration.

Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study.

BACKGROUND: Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. METHODS: We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR-Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR-Egger intercept test, MR-PRESSO global test, and leave-one-out method. RESULT: Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9, Eubacterium oxidoreducens group, and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. CONCLUSION: Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Revealing the genetic traits of the foodborne microbial genus hafnia: Implications for the human gut microbiome.

The bacterial genus Hafnia has recently attracted attention due to its complex metabolic features and host-interaction capabilities, which are associated with health benefits, primarily weight loss. However, significant gaps remain in our understanding of the genomic characteristics of this emerging microbial group. In this study, we utilized all available high-quality genomes of Hafnia alvei and Hafnia paralvei to uncover the broad distribution of Hafnia in human and honeybee guts, as well as in dairy products, by analysing 1068 metagenomic datasets. We then investigated the genetic traits related to Hafnia's production of vitamins and short-chain fatty acids (SCFAs) through a comparative genomics analysis that included all dominant bacterial species in the three environments under study. Our findings underscore the extensive metabolic capabilities of Hafnia, particularly in the production of vitamins such as thiamine (B1), nicotinate (B3), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12), and menaquinone (K2). Additionally, Hafnia demonstrated a conserved genetic makeup associated with SCFA production, including acetate, propanoate, and butanoate. These metabolic traits were further confirmed using RNAseq analyses of a newly isolated H. paralvei strain T10. Overall, our study illuminates the ecological distribution and genetic attributes of this bacterial genus, which is of increasing scientific and industrial relevance.

Cohabiting with ulcerative colitis patients decreases differences of gut microbiome between healthy individuals and the patients.

Background: Ulcerative colitis (UC), which is characterized by chronic relapsing inflammation of the colon, results from a complex interaction of factors involving the host, environment, and microbiome. The present study aimed to investigate the gut microbial composition and metabolic variations in patients with UC and their spouses. Materials and Methods: Fecal samples were collected from 13 healthy spouses and couples with UC. 16S rRNA gene amplicon sequencing and metagenomics sequencing were used to analyze gut microbiota composition, pathways, gene expression, and enzyme activity, followed by the Kyoto Encyclopedia of Genes and Genomes. Results: We found that the microbiome diversity of couples with UC decreased, especially that of UC patients. Bacterial composition, such as Firmicutes, was altered between UC patients and healthy controls, but was not significantly different between UC patients and their spouses. This has also been observed in pathways, such as metabolism, genetic information processing, organismal systems, and human diseases. However, the genes and enzymes of spouses with UC were not significantly different from those of healthy individuals. Furthermore, the presence of Faecalibacterium correlated with oxidative phosphorylation, starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and the bacterial secretion system, showed a marked decline in the UC group compared with their spouses, but did not vary between healthy couples. Conclusion: Our study revealed that cohabitation with UC patients decreased differences in the gut microbiome between healthy individuals and patients. Not only was the composition and diversity of the microbiota diminished, but active pathways also showed some decline. Furthermore, Firmicutes, Faecalibacterium, and the four related pathways may be associated with the pathological state of the host rather than with human behavior.

Pan-genome insights into adaptive evolution of bacterial symbionts in mixed host-microbe symbioses represented by human gut microbiota Bacteroides cellulosilyticus.

Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host's lifestyle. The link between microbial symbiosis and host development remains poorly understood. In particular, little is known about the adaptive evolution of gut bacteria in host-microbe symbioses. Recently, symbiotic relationships have been categorized as open, closed, or mixed, reflecting their modes of inter-host transmission and resulting in distinct genomic features. Members of the genus Bacteroides are the most abundant human gut microbiota and possess both probiotic and pathogenic potential, providing an excellent model for studying pan-genome evolution in symbiotic systems. Here, we determined the complete genome of an novel clinical strain PL2022, which was isolated from a blood sample and performed pan-genome analyses on a representative set of Bacteroides cellulosilyticus strains to quantify the influence of the symbiotic relationship on the evolutionary dynamics. B. cellulosilyticus exhibited correlated genomic features with both open and closed symbioses, suggesting a mixed symbiosis. An open pan-genome is characterized by abundant accessory gene families, potential horizontal gene transfer (HGT), and diverse mobile genetic elements (MGEs), indicating an innovative gene pool, mainly associated with genomic islands and plasmids. However, massive parallel gene loss, weak purifying selection, and accumulation of positively selected mutations were the main drivers of genome reduction in B. cellulosilyticus. Metagenomic read recruitment analyses showed that B. cellulosilyticus members are globally distributed and active in human gut habitats, in line with predominant vertical transmission in the human gut. However, existence and/or high abundance were also detected in non-intestinal tissues, other animal hosts, and non-host environments, indicating occasional horizontal transmission to new niches, thereby creating arenas for the acquisition of novel genes. This case study of adaptive evolution under a mixed host-microbe symbiosis advances our understanding of symbiotic pan-genome evolution. Our results highlight the complexity of genetic evolution in this unusual intestinal symbiont.

Blood lipids mediate the effects of gut microbiome on endometriosis: a mendelian randomization study.

BACKGROUND: There is evidence for an association between the gut microbiome and endometriosis. However, their causal relationship and the mediating role of lipid metabolism remain unclear. METHODS: Using genome-wide association study (GWAS) data, we conducted a bidirectional Mendelian randomization (MR) analysis to investigate the causal relationships between gut microbiome and endometriosis. The inverse variance weighted (IVW) method was used as the primary model, with other MR models used for comparison. Sensitivity analysis based on different statistical assumptions was used to evaluate whether the results were robust. A two-step MR analysis was further conducted to explore the mediating effects of lipids, by integrating univariable MR and the multivariate MR method based on the Bayesian model averaging method (MR-BMA). RESULTS: We identified four possible intestinal bacteria genera associated with the risk of endometriosis through the IVW method, including Eubacterium ruminantium group (odds ratio [OR] = 0.881, 95% CI: 0.795-0.976, P = 0.015), Anaerotruncus (OR = 1.252, 95% CI: 1.028-1.525, P = 0.025), Olsenella (OR = 1.110, 95% CI: 1.007-1.223, P = 0.036), and Oscillospira (OR = 1.215, 95% CI: 1.014-1.456, P = 0.035). The further two-step MR analysis identified that the effect of Olsenella on endometriosis was mediated by triglycerides (proportion mediated: 3.3%; 95% CI = 1.5-5.1%). CONCLUSION: This MR study found evidence for specific gut microbiomes associated with the risk of endometriosis, which might partially be mediated by triglycerides.

Landscapes of gut bacterial and fecal metabolic signatures and their relationship in severe preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. METHODS: In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. RESULTS: We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. CONCLUSION: Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.