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Frontiers in Immunology 2024Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in...
OBJECTIVE
Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in order to discover the microbiome-metabolome interface in AS. Based on prospective cohort studies, we further explored the impact of the tumor necrosis factor inhibitor (TNFi) on the gut microbiota and metabolites in AS.
METHODS
To further understand the gut microbiota and metabolites in AS, along with the influence of TNFi, we initiated a prospective cohort study. Fecal samples were collected from 29 patients with AS before and after TNFi therapy and 31 healthy controls. Metagenomic and metabolomic experiments were performed on the fecal samples; moreover, validation experiments were conducted based on the association between the microbiota and metabolites.
RESULTS
A total of 7,703 species were annotated using the metagenomic sequencing system and by profiling the microbial community taxonomic composition, while 50,046 metabolites were identified using metabolite profiling. Differential microbials and metabolites were discovered between patients with AS and healthy controls. Moreover, TNFi was confirmed to partially restore the gut microbiota and the metabolites. Multi-omics analysis of the microbiota and metabolites was performed to determine the associations between the differential microbes and metabolites, identifying compounds such as oxypurinol and biotin, which were correlated with the inhibition of the pathogenic bacteria and the promotion of the probiotic bacteria . Through experimental studies, the relationship between microbes and metabolites was further confirmed, and the impact of these two types of microbes on the enterocytes and the inflammatory cytokine interleukin-18 (IL-18) was explored.
CONCLUSION
In summary, multi-omics exploration elucidated the impact of TNFi on the gut microbiota and metabolites and proposed a novel therapeutic perspective: supplementation of compounds to inhibit potential pathogenic bacteria and to promote potential probiotics, therefore controlling inflammation in AS.
Topics: Humans; Spondylitis, Ankylosing; Gastrointestinal Microbiome; Probiotics; Male; Female; Metabolome; Adult; Feces; Metagenomics; Middle Aged; Prospective Studies; Metabolomics; Bacteria; Tumor Necrosis Factor Inhibitors
PubMed: 38711505
DOI: 10.3389/fimmu.2024.1369116 -
Frontiers in Pharmacology 2024Herbal formulations are renowned for their complex biological activities, acting on multiple targets and pathways, as evidenced by studies. However, the hypoglycemic...
Herbal formulations are renowned for their complex biological activities, acting on multiple targets and pathways, as evidenced by studies. However, the hypoglycemic effect and underlying mechanisms of Shenqi Compound (SQ), a traditional Chinese herbal formula, remain elusive. This study aimed to elucidate the hypoglycemic effects of SQ and explore its mechanisms of action, focusing on intestinal flora and metabolomics. A Type 2 diabetes mellitus (T2DM) rat model was established through a high-fat diet, followed by variable glucose and insulin injections to mimic the fluctuating glycemic conditions seen in diabetes. An eight-week regimen of SQ significantly mitigated hyperglycemia, inflammation, and insulin resistance in these rats. Notably, SQ beneficially modulated the gut microbiota by increasing populations of beneficial bacteria, such as Lachnospiraceae_NK4A136_group and Akkermansia, while reducing and inhibiting harmful strains such as Ruminococcus and Phascolarctobacterium. Metabolomics analyses revealed that SQ intervention corrected disturbances in Testosterone enanthate and Glycerophospholipid metabolism. Our findings highlight the hypoglycemic potential of SQ and its mechanisms via modulation of the gut microbiota and metabolic pathways, offering a theoretical foundation for the use of herbal medicine in diabetes management.
PubMed: 38708085
DOI: 10.3389/fphar.2024.1349244 -
Journal of Animal Science and... May 2024Dietary supplementation of xylooligosaccharides (XOS) has been found to influence gut health by manipulating cecal microbiota and producing microbe-origin metabolites....
Effect of in ovo feeding of xylobiose and xylotriose on plasma immunoglobulin, cecal metabolites production, microbial ecology, and metabolic pathways in broiler chickens.
BACKGROUND
Dietary supplementation of xylooligosaccharides (XOS) has been found to influence gut health by manipulating cecal microbiota and producing microbe-origin metabolites. But no study investigated and compared the effect of in ovo feeding of xylobiose (XOS2) and xylotriose (XOS3) in chickens. This study investigated the effect of in ovo feeding of these XOS compounds on post-hatch gut health parameters in chickens. A total of 144 fertilized chicken eggs were divided into three groups: a) non-injected control (CON), b) XOS2, and c) XOS3. On the 17 embryonic day, the eggs of the XOS2 and XOS3 groups were injected with 3 mg of XOS2 and XOS3 diluted in 0.5 mL of 0.85% normal saline through the amniotic sac. After hatching, the chicks were raised for 21 d. Blood was collected on d 14 to measure plasma immunoglobulin. Cecal digesta were collected for measuring short-chain fatty acids (SCFA) on d 14 and 21, and for microbial ecology and microbial metabolic pathway analyses on d 7 and 21.
RESULTS
The results were considered significantly different at P < 0.05. ELISA quantified plasma IgA and IgG on d 14 chickens, revealing no differences among the treatments. Gas chromatography results showed no significant differences in the concentrations of cecal SCFAs on d 14 but significant differences on d 21. However, the SCFA concentrations were lower in the XOS3 than in the CON group on d 21. The cecal metagenomics data showed that the abundance of the family Clostridiaceae significantly decreased on d 7, and the abundance of the family Oscillospiraceae increased on d 21 in the XOS2 compared to the CON. There was a reduction in the relative abundance of genus Clostridium sensu stricto 1 in the XOS2 compared to the CON on d 7 and the genus Ruminococcus torques in both XOS2 and XOS3 groups compared to the CON on d 21. The XOS2 and XOS3 groups reduced the genes for chondroitin sulfate degradation I and L-histidine degradation I pathways, which contribute to improved gut health, respectively, in the microbiome on d 7. In contrast, on d 21, the XOS2 and XOS3 groups enriched the thiamin salvage II, L-isoleucine biosynthesis IV, and O-antigen building blocks biosynthesis (E. coli) pathways, which are indicative of improved gut health. Unlike the XOS3 and CON, the microbiome enriched the pathways associated with energy enhancement, including flavin biosynthesis I, sucrose degradation III, and Calvin-Benson-Bassham cycle pathways, in the XOS2 group on d 21.
CONCLUSION
In ovo XOS2 and XOS3 feeding promoted beneficial bacterial growth and reduced harmful bacteria at the family and genus levels. The metagenomic-based microbial metabolic pathway profiling predicted a favorable change in the availability of cecal metabolites in the XOS2 and XOS3 groups. The modulation of microbiota and metabolic pathways suggests that in ovo XOS2 and XOS3 feeding improved gut health during the post-hatch period of broilers.
PubMed: 38702804
DOI: 10.1186/s40104-024-01022-7 -
Frontiers in Immunology 2024Several observational studies have proposed a potential link between gut microbiota and the onset and progression of sepsis. Nevertheless, the causality of gut...
BACKGROUND
Several observational studies have proposed a potential link between gut microbiota and the onset and progression of sepsis. Nevertheless, the causality of gut microbiota and sepsis remains debatable and warrants more comprehensive exploration.
METHODS
We conducted a two-sample Mendelian randomization (MR) analysis to test the causality between gut microbiota and the onset and progression of sepsis. The genome-wide association study (GWAS) summary statistics for 196 bacterial traits were extracted from the MiBioGen consortium, whereas the GWAS summary statistics for sepsis and sepsis-related outcomes came from the UK Biobank. The inverse-variance weighted (IVW) approach was the primary method used to examine the causal association. To complement the IVW method, we utilized four additional MR methods. We performed a series of sensitivity analyses to examine the robustness of the causal estimates.
RESULTS
We assessed the causality of 196 bacterial traits on sepsis and sepsis-related outcomes. Genus [odds ratio (OR) 0.81, 95% confidence interval (CI) (0.69-0.94), = 0.007] and genus (OR 0.85, 95% CI 0.74-0.97, = 0.016) had a protective effect on sepsis, whereas genus (OR 1.10, 95% CI 1.01-1.20, = 0.024) increased the risk of sepsis. When it came to sepsis requiring critical care, genus (OR 0.49, 95% CI 0.31-0.76, = 0.002), genus (OR 0.65, 95% CI 0.43-1.00, = 0.049), and genus (OR 0.51, 95% CI 0.34-0.77, = 0.001) emerged as protective factors. Concerning 28-day mortality of sepsis, genus (OR 0.67, 95% CI 0.48-0.94, = 0.020), genus (OR 0.48, 95% CI 0.27-0.86, = 0.013), genus (OR 0.70, 95% CI 0.52-0.95, = 0.023), and genus (OR 0.82, 95% CI 0.68-0.99, = 0.042) presented a protective effect, whereas genus (OR 1.53, 95% CI 1.00-2.35, = 0.049), genus (OR 1.25, 95% CI 1.04-1.50, = 0.019), and genus (OR 1.43, 95% CI 1.02-2.02, = 0.040) presented a harmful effect. Furthermore, genus (OR 0.42, 95% CI 0.19-0.92, = 0.031), genus (OR 0.34, 95% CI 0.14-0.83, = 0.018), and genus (OR 0.43, 95% CI 0.22-0.83, = 0.012) were associated with a lower 28-day mortality of sepsis requiring critical care.
CONCLUSION
This MR analysis unveiled a causality between the 21 bacterial traits and sepsis and sepsis-related outcomes. Our findings may help the development of novel microbiota-based therapeutics to decrease the morbidity and mortality of sepsis.
Topics: Humans; Sepsis; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Genome-Wide Association Study; Disease Progression; Polymorphism, Single Nucleotide
PubMed: 38698853
DOI: 10.3389/fimmu.2024.1266579 -
Investigative Ophthalmology & Visual... May 2024To identify compositional differences in the gut microbiome of nonmyopes (NM) and myopes using 16S ribosomal RNA sequencing and to investigate whether the microbiome may...
PURPOSE
To identify compositional differences in the gut microbiome of nonmyopes (NM) and myopes using 16S ribosomal RNA sequencing and to investigate whether the microbiome may contribute to the onset or progression of the condition.
METHODS
Faecal samples were collected from 52 adult participants, of whom 23 were NM, 8 were progressive myopes (PM), and 21 were stable myopes (SM). The composition of the gut microbiota in each group was analysed using 16S ribosomal RNA gene sequencing.
RESULTS
There were no significant differences in alpha and beta diversity between the three groups (NM, PM, and SM). However, the distributions of Bifidobacterium, Bacteroides, Megamonas, Faecalibacterium, Coprococcus, Dorea, Roseburia, and Blautia were significantly higher in the myopes (SM and PM combined) when compared with emmetropes. The myopes exhibited significantly greater abundance of bacteria that are linked to the regulation of dopaminergic signalling, such as Clostridium, Ruminococcus, Bifidobacterium, and Bacteroides. Individuals with stable myopia were found to have a significantly higher proportion of Prevotella copri than those with progressive myopia. Bifidobacterium adolescentis, a gamma-aminobutyric acid (GABA)-producing bacterium, was significantly higher in all myopes than in NM and, in the comparison between SM and PM, it is significantly higher in SM. B. uniformis and B. fragilis, both GABA-producing Bacteroides, were present in relatively high abundance in all myopes and in SM compared with PM, respectively.
CONCLUSIONS
The presence of bacteria related to dopamine effect and GABA-producing bacteria in the gut microbiome of myopes may suggest a role of these microorganisms in the onset and progression of myopia.
Topics: Humans; Male; Adult; Female; Gastrointestinal Microbiome; Feces; RNA, Ribosomal, 16S; Myopia; Bacteria; Young Adult; Middle Aged; DNA, Bacterial
PubMed: 38691091
DOI: 10.1167/iovs.65.5.2 -
Microbiology Spectrum Jun 2024Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable , , and tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera and , as well as the species , showed significantly higher relative abundances compared to the control group (CG) ( < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG ( < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG ( < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism ( < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and pathogenic cycle ( < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women.
IMPORTANCE
Probiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism. This could potentially open up new avenues for preventing various pregnancy-related complications. This also provides new insights into the effects of probiotic consumption during pregnancy on the gut microbiota and offers a convenient method for exploring the potential mechanisms underlying the impact of probiotics on the gut microbiota of pregnant women.
Topics: Humans; Female; Gastrointestinal Microbiome; Probiotics; Pregnancy; Adult; RNA, Ribosomal, 16S; Bacteria; Feces; Streptococcus thermophilus; Bifidobacterium longum; Young Adult; Lactobacillus delbrueckii
PubMed: 38687069
DOI: 10.1128/spectrum.00413-24 -
Scientific Reports Apr 2024Gut microbiome dysbiosis contributes to the pathophysiology of both gestational diabetes mellitus (GDM) and its associated adverse outcomes in the woman and offspring....
Gut microbiome dysbiosis contributes to the pathophysiology of both gestational diabetes mellitus (GDM) and its associated adverse outcomes in the woman and offspring. Even though GDM prevalence, complications, and outcomes vary among different ethnic groups, limited information is available about the influence of ethnicity on gut microbiome dysbiosis in pregnancies complicated by GDM. This pilot prospective cohort study examined the impact of ethnicity on gut dysbiosis in GDM among three Asian ethnic groups (Chinese, Malay, Indian) living in Singapore, and investigated the potential modulatory roles of diet and lifestyle modifications on gut microbiome post-GDM diagnosis. Women with GDM (n = 53) and without GDM (n = 16) were recruited. Fecal samples were collected at 24-28- and 36-40-weeks' gestation and analyzed by targeted 16S rRNA gene-based amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) analysis was performed to evaluate differences between groups. Differentially abundant taxa were identified by DeSeq2 based analysis. Functional prediction was performed using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). Among women with GDM, gut microbiome from different ethnicities harbored common microbial features. However, among those without GDM, there was contrasting microbiome composition between ethnic groups. Microbial members such as Collinsella, Blautia, Ruminococcus, Ruminococcus gnavus, Ruminococcus torques, and Eubacterium hallii groups were differentially enriched (p < 0.05) in women with GDM compared to those without. Among women with GDM, no differences in alpha- and beta- diversity were observed when comparing 24-28 weeks' samples with 36-40 weeks' samples, a period covering intense dietary and lifestyle modification, suggesting an inability to modulate gut microbiota through classic GDM management. Women with GDM have a distinct gut microbiome profile which harbours common features across different Asian ethnic groups, consistent with the notion that specific microbes are involved in the pathogenesis of insulin resistance, pro-inflammatory conditions, and other metabolic dysregulation known to be present in GDM.
Topics: Humans; Female; Pregnancy; Gastrointestinal Microbiome; Diabetes, Gestational; Dysbiosis; Pilot Projects; Adult; Singapore; Prospective Studies; Asian People; RNA, Ribosomal, 16S; Diet; Ethnicity; Feces; Bacteria
PubMed: 38684759
DOI: 10.1038/s41598-024-60386-y -
Nature Communications Apr 2024The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large...
The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.
Topics: Humans; Female; Gastrointestinal Microbiome; Middle Aged; Diverticulitis; Feces; Aged; Prospective Studies; Bilophila; Metabolomics; Case-Control Studies; Clostridiales; Bile Acids and Salts; Adult; Dietary Fiber; Metabolome; Metagenomics
PubMed: 38684664
DOI: 10.1038/s41467-024-47859-4 -
Frontiers in Microbiology 2024infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut...
infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ ( = 20) and CDI- ( = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens and in CDI+ compared to CDI- samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI-, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by . This provides evidence of another possible contributor to 's resistance to antibiotics and frequent recurrence . Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI.
PubMed: 38680911
DOI: 10.3389/fmicb.2024.1398018 -
Computational and Structural... Dec 2024Antlers are hallmark organ of deer, exhibiting a relatively high growth rate among mammals, and requiring large amounts of nutrients to meet its development. The rumen...
Antlers are hallmark organ of deer, exhibiting a relatively high growth rate among mammals, and requiring large amounts of nutrients to meet its development. The rumen microbiota plays key roles in nutrient metabolism. However, changes in the microbiota and metabolome in the rumen during antler growth are largely unknown. We investigated rumen microbiota (liquid, solid, ventral epithelium, and dorsal epithelium) and metabolic profiles of sika deer at the early (EG), metaphase (MG) and fast growth (FG) stages. Our data showed greater concentrations of acetate and propionate in the rumens of sika deer from the MG and FG groups than in those of the EG group. However, microbial diversity decreased during antler growth, and was negatively correlated with short-chain fatty acid (SCFA) levels. , , and were the dominant bacteria in the liquid, solid, ventral epithelium, and dorsal epithelium fractions. The proportions of , , and increased significantly in the liquid or dorsal epithelium fractions. Untargeted metabolomics analysis revealed that the metabolites also changed significantly, revealing 237 significantly different metabolites, among which the concentrations of γ-aminobutyrate and creatine increased during antler growth. Arginine and proline metabolism and alanine, aspartate and glutamate metabolism were enhanced. The co-occurrence network results showed that the associations between the rumen microbiota and metabolites different among the three groups. Our results revealed that the different rumen ecological niches were characterized by distinct microbiota compositions, and the production of SCFAs and the metabolism of specific amino acids were significantly changed during antler growth.
PubMed: 38680874
DOI: 10.1016/j.csbj.2024.04.018