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BMC Pulmonary Medicine Apr 2024Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated...
BACKGROUND
Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation.
METHODS
Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed.
RESULTS
Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5.
CONCLUSIONS
Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.
Topics: Humans; Pulmonary Arterial Hypertension; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Familial Primary Pulmonary Hypertension; Choline; Methylamines
PubMed: 38632547
DOI: 10.1186/s12890-024-03008-7 -
Microbiome Jul 2023Understanding how the host's microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant...
BACKGROUND
Understanding how the host's microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant breeders. Currently, selection for resilience is considered a critical step in improving the sustainability of livestock systems. Environmental variance (V ), the within-individual variance of a trait, has been successfully used as a proxy for animal resilience. Selection for reduced V could effectively shift gut microbiome composition; reshape the inflammatory response, triglyceride, and cholesterol levels; and drive animal resilience. This study aimed to determine the gut microbiome composition underlying the V of litter size (LS), for which we performed a metagenomic analysis in two rabbit populations divergently selected for low (n = 36) and high (n = 34) V of LS. Partial least square-discriminant analysis and alpha- and beta-diversity were computed to determine the differences in gut microbiome composition among the rabbit populations.
RESULTS
We identified 116 KEGG IDs, 164 COG IDs, and 32 species with differences in abundance between the two rabbit populations studied. These variables achieved a classification performance of the V rabbit populations of over than 80%. Compared to the high V population, the low V (resilient) population was characterized by an underrepresentation of Megasphaera sp., Acetatifactor muris, Bacteroidetes rodentium, Ruminococcus bromii, Bacteroidetes togonis, and Eggerthella sp. and greater abundances of Alistipes shahii, Alistipes putredinis, Odoribacter splanchnicus, Limosilactobacillus fermentum, and Sutterella, among others. Differences in abundance were also found in pathways related to biofilm formation, quorum sensing, glutamate, and amino acid aromatic metabolism. All these results suggest differences in gut immunity modulation, closely related to resilience.
CONCLUSIONS
This is the first study to show that selection for V of LS can shift the gut microbiome composition. The results revealed differences in microbiome composition related to gut immunity modulation, which could contribute to the differences in resilience among rabbit populations. The selection-driven shifts in gut microbiome composition should make a substantial contribution to the remarkable genetic response observed in the V rabbit populations. Video Abstract.
Topics: Animals; Rabbits; Gastrointestinal Microbiome; Feces; Microbiota; Phenotype; Metagenome
PubMed: 37400907
DOI: 10.1186/s40168-023-01580-4 -
Research Square Aug 2023The relationships between psychosocial stress and diet with gut microbiota composition and diversity deserve ongoing investigation. The primary aim of this study was to...
A cross-sectional study observing the association of psychosocial stress and dietary intake with gut microbiota genera and alpha diversity among a young adult cohort of black and white women in Birmingham, Alabama.
BACKGROUND
The relationships between psychosocial stress and diet with gut microbiota composition and diversity deserve ongoing investigation. The primary aim of this study was to examine the associations of psychosocial stress measures and dietary variables with gut microbiota genera abundance and alpha diversity among young adult, black and white females. The secondary aim was to explore mediators of psychosocial stress and gut microbiota diversity and abundance.
METHODS
Data on 60 females who self-identified as African American (AA; n = 29) or European American (EA; n = 31) aged 21-45 years were included. Cortisol was measured in hair and saliva, and 16S analysis of stool samples were conducted. Discrimination experiences (recent and lifetime), perceived stress, and depression were evaluated based on validated instruments. Spearman correlations were performed to evaluate the influence of psychosocial stressors, cortisol measures, and dietary variables on gut microbiota genus abundance and alpha diversity measured by amplicon sequence variant(ASV) count. Mediation analyses assessed the mediating role of select dietary variables and cortisol measures on the associations between psychosocial stress, and abundance, and ASV count.
RESULTS
AA females were found to have significantly lower ASV count and abundance. Results for the spearman correlations assessing the influence of psychosocial stress and dietary variables on gut microbiota abundance and ASV count were varied. Finally, diet nor cortisol was found to partially or fully mediate the associations between subjective stress measures, ASV count, and and abundance.
CONCLUSION
In this cross-sectional study, AA females had lower alpha diversity and abundance compared to EA females. Some psychosocial stressors and dietary variables were found to be correlated with ASV count and few gut microbiota genera. Larger scale studies are needed to explore the relationships among psychosocial stress, diet and the gut microbiome.
PubMed: 37609244
DOI: 10.21203/rs.3.rs-3146763/v1 -
Frontiers in Microbiology 2024The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the...
INTRODUCTION
The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the causal impact of GM on LC and identify potential immune cell mediators.
METHODS
The utilized data for the Genome-Wide Association Studies (GWAS) were summarized as follows: gut microbiota data from the Dutch Microbiome Project (DMP) ( = 7,738), lung cancer data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and International Lung Cancer Consortium (ILCCO) ( = 29,266, = 56,450) included four types of cancer: NSCLC, LUAD, LUSC, and SCLC, and immune cell data from European populations ( = 3,757). We employed bi-directional two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and mediation analysis to assess the causal relationship between GM and LC and potential immune cell mediators.
RESULTS
Bi-directional UVMR analysis revealed that 24 gut microbiota species can affect LC, while LC can affect the abundance of 17 gut microbiota species. Mediation analysis demonstrated that six immune cells mediated the causal relationships of seven gut microbiota species on LC: "CCR7 on naive CD8+ T cell" mediated the causal relationship between s_Alistipes_putredinis and LUAD, with a mediation proportion of 9.5% and = 0.018; "IgD- CD27- B cell %lymphocyte" mediated the causal relationships between g_Gordonibacter and s_Gordonibacter_pamelaeae with LUSC, with mediation proportions of 11.8% and 11.9%, respectively and = 0.029; "CD20- CD38- B cell %lymphocyte" mediated the causal relationship between s_Bacteroides_clarus and SCLC, with a mediation proportion of 13.8% and = 0.005; "CD20 on IgD+ CD38- unswitched memory B cell" mediated the causal relationship between s_Streptococcus_thermophilus and SCLC, with a mediation proportion of 14.1% and = 0.023; "HLA DR on CD14- CD16+ monocyte" mediated the causal relationship between s_Bifidobacterium_bifidum and SCLC, with a mediation proportion of 8.7% and = 0.012; "CD45 on Granulocytic Myeloid-Derived Suppressor Cells" mediated the causal relationship between f_Lactobacillaceae and SCLC, with a mediation proportion of 4.0% and = 0.021.
CONCLUSION
This Mendelian randomization study identified several specific gut microbiotas that exhibit causal relationships with lung cancer and potentially mediate immune cells.
PubMed: 38765682
DOI: 10.3389/fmicb.2024.1390722 -
Journal of Neuroinflammation Sep 2023The contribution of the gut microbiome to neuroinflammation, cognition, and Alzheimer's disease progression has been highlighted over the past few years. Additionally,...
The contribution of the gut microbiome to neuroinflammation, cognition, and Alzheimer's disease progression has been highlighted over the past few years. Additionally, inhibition of various components of the complement system has repeatedly been demonstrated to reduce neuroinflammation and improve cognitive performance in AD mouse models. Whether the deletion of these complement components is associated with distinct microbiome composition, which could impact neuroinflammation and cognitive performance in mouse models has not yet been examined. Here, we provide a comprehensive analysis of conditional and constitutive knockouts, pharmacological inhibitors, and various housing paradigms for the animal models and wild-type controls at various ages. We aimed to determine the impact of C1q or C5aR1 inhibition on the microbiome in the Arctic and Tg2576 mouse models of AD, which develop amyloid plaques at different ages and locations. Analysis of fecal samples from WT and Arctic mice following global deletion of C1q demonstrated significant alterations to the microbiomes of Arctic but not WT mice, with substantial differences in abundances of Erysipelotrichales, Clostridiales and Alistipes. While no differences in microbiome diversity were detected between cohoused wildtype and Arctic mice with or without the constitutive deletion of the downstream complement receptor, C5aR1, a difference was detected between the C5aR1 sufficient (WT and Arctic) and deficient (C5ar1KO and ArcticC5aR1KO) mice, when the mice were housed segregated by C5aR1 genotype. However, cohousing of C5aR1 sufficient and deficient wildtype and Arctic mice resulted in a convergence of the microbiomes and equalized abundances of each identified order and genus across all genotypes. Similarly, pharmacologic treatment with the C5aR1 antagonist, PMX205, beginning at the onset of beta-amyloid plaque deposition in the Arctic and Tg2576 mice, demonstrated no impact of C5aR1 inhibition on the microbiome. This study demonstrates the importance of C1q in microbiota homeostasis in neurodegenerative disease. In addition, while demonstrating that constitutive deletion of C5aR1 can significantly alter the composition of the fecal microbiome, these differences are not present when C5aR1-deficient mice are cohoused with C5aR1-sufficient animals with or without the AD phenotype and suggests limited if any contribution of the microbiome to the previously observed prevention of cognitive and neuronal loss in the C5aR1-deficient AD models.
Topics: Animals; Mice; Alzheimer Disease; Complement C1q; Disease Models, Animal; Gastrointestinal Microbiome; Neurodegenerative Diseases; Neuroinflammatory Diseases; Receptors, Complement
PubMed: 37726739
DOI: 10.1186/s12974-023-02885-9 -
BMC Microbiology Jul 2023Intestinal flora has been proposed to mediate the occurrence of postmenopausal osteoporosis (PMO). However, the mechanism by which microbes and their metabolites...
BACKGROUND
Intestinal flora has been proposed to mediate the occurrence of postmenopausal osteoporosis (PMO). However, the mechanism by which microbes and their metabolites interactively promote PMO remains unknown.
METHODS
This study aimed to investigate changes in the intestinal flora and associated metabolites, and their role in PMO. 16S rRNA gene sequencing and metabolomics were performed to obtain postmenopausal women with osteopenia (lower bone mass, LBM), postmenopausal women with osteoporosis (OST), and healthy women as the control group.
RESULTS
We identified taxa-specific and metabolite differences in the intestinal flora of the participants of this study. The pathogenic bacteria Klebsiella (0.59% and 0.71%, respectively) and Escherichia-Shigella (2.72% and 4.30%, respectively) were enriched in the LBM and OST groups (p < 0.05). Some short-chain fatty acid (SCFAs) producing bacteria, Lactobacillus, Akkermansia, Prevotella, Alistipes, and Butyricicoccus, were reduced in patients with LBM and OST compared to the control. Moreover, fecal metabolomic analyses suggested that the metabolites of indole-3-acetic acid and 7-ketodeoxycholic acid were altered in the LBM and OST groups compared to the control (p < 0.05). Enrichment analysis suggested that valine, leucine, and isoleucine biosynthesis; aromatic amino acid biosynthesis; and phenylalanine metabolism were significantly associated with the identified microbiota biomarkers and OST. Moreover, metabolite marker signatures distinguished patients in the OST from those in the control group with an area under the curve (AUC) of 0.978 and 1.00 in the negative and positive ion modes, respectively. Finally, we also found that the fecal level of interleukin-10 (IL-10) in the OST group was significantly lower than that in the control group and LBM group (p < 0.05), while tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly higher in the OST group than that in the control group (p < 0.05).
CONCLUSIONS
This study provides robust evidence connecting the intestinal flora and fecal metabolomics with PMO. Integrated metabolite and microbiota analyses demonstrated that in addition to dysregulated bacteria, indole-3-acetic acid, 7-ketodeoxycholic acid, and other metabolites can be used for the distinguish of LBM and PMO.
Topics: Humans; Female; Osteoporosis, Postmenopausal; RNA, Ribosomal, 16S; Bone Density; Metabolomics; Interleukin-6; Amino Acids
PubMed: 37495941
DOI: 10.1186/s12866-023-02927-5 -
Frontiers in Endocrinology 2023Bone mass accumulated in early adulthood is an important determinant of bone mass throughout the lifespan, and inadequate bone deposition may lead to associated skeletal...
INTRODUCTION
Bone mass accumulated in early adulthood is an important determinant of bone mass throughout the lifespan, and inadequate bone deposition may lead to associated skeletal diseases. Recent studies suggest that gut bacteria may be potential factors in boosting bone mass. Strontium (Sr) as a key bioactive element has been shown to improve bone quality, but the precise way that maintains the equilibrium of the gut microbiome and bone health is still not well understood.
METHODS
We explored the capacity of SrCl2 solutions of varying concentrations (0, 100, 200 and 400 mg/kg BW) on bone quality in 7-week-old male Wistar rats and attempted to elucidate the mechanism through gut microbes.
RESULTS
The results showed that in a Wistar rat model under normal growth conditions, serum Ca levels increased after Sr-treatment and showed a dose-dependent increase with Sr concentration. Three-point mechanics and Micro-CT results showed that Sr exposure enhanced bone biomechanical properties and improved bone microarchitecture. In addition, the osteoblast gene markers , , and mRNA levels were significantly increased to varying degrees after Sr treatment, and the osteoclast markers RANKL and TRAP were accompanied by varying degrees of reduction. These experimental results show that Sr improves bones from multiple angles. Further investigation of the microbial population revealed that the composition of the gut microbiome was changed due to Sr, with the abundance of 6 of the bacteria showing a different dose dependence with Sr concentration than the control group. To investigate whether alterations in bacterial flora were responsible for the effects of Sr on bone remodeling, a further pearson correlation analysis was done, 4 types of bacteria (, , and ) were deduced to be the primary contributors to Sr-relieved bone loss. Of these, we focused our analysis on the most firmly associated .
DISCUSSION
To summarize, our current research explores changes in bone mass following Sr intervention in young individuals, and the connection between Sr-altered intestinal flora and potentially beneficial bacteria in the attenuation of bone loss. These discoveries underscore the importance of the "gut-bone" axis, contributing to an understanding of how Sr affects bone quality, and providing a fresh idea for bone mass accumulation in young individuals and thereby preventing disease due to acquired bone mass deficiency.
Topics: Rats; Male; Animals; Bone Density; Gastrointestinal Microbiome; Rats, Wistar; Strontium; Bone Diseases, Metabolic
PubMed: 37795367
DOI: 10.3389/fendo.2023.1198475 -
Microorganisms Sep 2023Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We...
Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We analyzed Iwaki health check-up data collected from 2017 to 2019 and constructed generalized linear mixed models. The independent variable was the relative abundance of each of the 37 gut microbiota genera that were reported to be associated with depression. The dependent variable was the presence of depression assessed by the Center for Epidemiologic Studies Depression Scale. Potential confounders, including grip strength, gender, height, weight, smoking, and drinking habits, were adjusted in the regression models. Nine genera's regression coefficients (, , , , , , , , and ) showed statistical significance after multiple comparisons adjustment. Among these nine gut bacteria genera, , , , , , and were reported to be associated with butyrate production in the intestine. Our results indicate that gut microbiotas may influence the depression condition of the host via the butyrate-producing process.
PubMed: 37764129
DOI: 10.3390/microorganisms11092286 -
Frontiers in Microbiology 2024The host genes play a crucial role in shaping the composition and structure of the gut microbiome. Red deer is listed as an endangered species by the International Union...
The host genes play a crucial role in shaping the composition and structure of the gut microbiome. Red deer is listed as an endangered species by the International Union for the Conservation of Nature, and its pilose antlers have good medicinal value. Hybridization can lead to heterosis, resulting in increased pilose antler production and growth performance in hybrid deer. However, the role of the gut microbiome in hybrid deer remains largely unknown. In this study, alpha and beta diversity analysis showed that hybridization altered the composition and structure of the gut microbiome of the offspring, with the composition and structure of the hybrid offspring being more similar to those of the paternal parents. Interestingly, the LefSe differential analysis showed that there were some significantly enriched gut microbiome in the paternal parents (such as , , etc.) and the maternal parents (including , , etc.), which remained significantly enriched in the hybrid offspring. Additionally, the hybrid offspring exhibited a significant advantage over the parental strains, particularly in taxa that can produce short-chain fatty acids, such as , , and . Similar to bacterial transmission, metagenomic analysis showed that some signaling pathways related to pilose antler growth ("Wnt signaling pathway," "PI3K Akt signaling pathway," "MAPK signaling pathway") were also enriched in hybrid red deer after hybridization. Furthermore, metabolomic analysis revealed that compared with the paternal and maternal parents, the hybrid offspring exhibited significant enrichment in metabolites related to "Steroid hormone biosynthesis," "Tryptophan metabolism," "Valine, leucine and isoleucine metabolism," and "Vitamin B metabolism." Notably, the metagenomic analysis also showed that these metabolic pathways were significantly enriched in hybrid deer. Finally, a correlation analysis between the gut microbiome and metabolites revealed a significant positive correlation between the enriched taxa in hybrid deer, including the , , and , and metabolites, such as 7α-hydroxytestosterone, L-kynurenine, indole, L-isoleucine, and riboflavin. The study contributes valuable data toward understanding the role of the gut microbiome from red deer in hybridization and provides reference data for further screening potential probiotics and performing microbial-assisted breeding that promotes the growth of red deer pilose antlers and bodies, development, and immunity.
PubMed: 38784815
DOI: 10.3389/fmicb.2024.1387957 -
Science Advances Dec 2023Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We...
Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We investigated the relationship between the microbiome and neuroanatomy and cognition of 381 healthy children, demonstrating that differences in microbial taxa and genes are associated with overall cognitive function and the size of brain regions. Using a combination of statistical and machine learning models, we showed that species including , , and were enriched or depleted in children with higher cognitive function scores. Microbial metabolism of short-chain fatty acids was also associated with cognitive function. In addition, machine models were able to predict the volume of brain regions from microbial profiles, and taxa that were important in predicting cognitive function were also important for predicting individual brain regions and specific subscales of cognitive function. These findings provide potential biomarkers of neurocognitive development and may enable development of targets for early detection and intervention.
Topics: Child; Humans; Neuroanatomy; Feces; Cognition; Brain; Gastrointestinal Microbiome
PubMed: 38134274
DOI: 10.1126/sciadv.adi0497