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Frontiers in Microbiology 2023The gut microbiota has emerged as an intriguing and potentially influential factor in regulating bone health. However, the causal effect of the gut microbiota on bone...
BACKGROUND
The gut microbiota has emerged as an intriguing and potentially influential factor in regulating bone health. However, the causal effect of the gut microbiota on bone mineral density (BMD) appears to differ throughout various life stages.
METHODS
We conducted a Mendelian randomization (MR) analysis to investigate the potential causal relationship between gut microbiota and BMD in five distinct age groups: 0-15, 15-30, 30-45, 45-60, and 60 years and older. The analysis employed three different methods, namely MR-Egger, weighted median, and Inverse-variance weighting, to ensure the robustness of our findings, a series of sensitivity analyses were also conducted, such as horizontal pleiotropy tests, heterogeneity tests, and leave-one-out sensitivity tests.
RESULTS
In the age group of 0-15 years, _group and _group were identified as risk factors for BMD. During the 15-30 age group, , , and _UCG_003 were found to be protective factors for BMD. In the 30-45 age group, genus demonstrated a protective effect on BMD, while and were identified as risk factors for BMD. Moving on to the 45-60 age group, _group, _UCG_004, and were observed to be protective factors for BMD, while _group, , and were associated with an increased risk of BMD. In individuals aged 60 years and older, and _UCG_002 were also noted as risk factors for BMD. Conversely, _group, _group, , and _3 were found to be protective factors for BMD, whereas and were identified as risk factors for BMD.
CONCLUSION
A robust causal relationship between gut microbiota and bone mineral density (BMD) exists throughout all stages of life, with Firmicutes phylum being the primary group associated with BMD across age groups. Gut microbiota linked with BMD primarily belong to the Firmicutes phylum across age groups. The diversity of gut microbiota phyla associated with BMD depicts relatively stable patterns during the ages of 0-45 years. However, for individuals aged 45 years and above, there is an observed increase in the number of gut microbiota species linked with BMD, and by the age of 60 years, a trend toward an increase in the Bacteroidetes phylum categories is proposed.
PubMed: 37937216
DOI: 10.3389/fmicb.2023.1268935 -
BMC Pregnancy and Childbirth Aug 2023Previous observational cohort studies have shown that the composition of the gut microbiota is related to the risk of intrahepatic cholestasis of pregnancy (ICP),...
BACKGROUND
Previous observational cohort studies have shown that the composition of the gut microbiota is related to the risk of intrahepatic cholestasis of pregnancy (ICP), although it is unclear if the association is causative. This study used Mendelian randomization (MR) to systematically examine whether the gut microbiota was causally linked to ICP.
METHODS
We obtained the genome-wide association study (GWAS) summary statistics of gut microbiota and ICP from published GWASs. Maximum likelihood (ML), MR-Egger regression, weighted median, inverse variance weighted (IVW), and weighted model were used to investigate the causal association between gut microbiota and ICP. We further conducted a series of sensitivity analyses to confirm the robustness of the primary results of the MR analyses. Reverse MR analysis was performed on the bacterial taxa that were reported to be causally linked to ICP risk in forwarding MR analysis to evaluate the possibility of reverse causation.
RESULTS
MR analysis revealed that phylum Tenericutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), class Bacteroidia (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), class Mollicutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), and order Bacteroidales (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), and were positively associated with the risk of ICP. And we identified that the relative abundance of genus Dialister (OR: 0.562, 95%CI: 0.323-0.977, P = 0.041), genus Erysipelatoclostridium (OR: 0.695, 95%CI: 0.490-0.987, P = 0.042), genus Eubacterium (brachy group) (OR: 0.661, 95%CI: 0.497-0.880, P = 0.005), genus Eubacterium (hallii group) (OR: 0.664, 95%CI: 0.451-0.977, P = 0.037), genus Holdemania (OR: 0.590, 95%CI: 0.414-0.840, P = 0.003), genus Ruminococcus (torques group) (OR: 0.448, 95%CI: 0.235-0.854, P = 0.015), and genus Veillonella (OR: 0.513, 95%CI: 0.294-0.893, P = 0.018) were related to a lower risk of ICP. Additional sensitivity analyses confirmed the robustness of the association between specific gut microbiota composition and ICP. No evidence of reverse causality from ICP to identified bacterial taxa was found in the findings of the reverse MR analyses.
CONCLUSIONS
Under MR assumptions, our findings propose new evidence of the relationship between gut microbiota and ICP risk. Our results show that the gut microbiota may be useful target of intervention for ICP.
Topics: Female; Pregnancy; Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Bacteroidetes
PubMed: 37543573
DOI: 10.1186/s12884-023-05889-8 -
Frontiers in Immunology 2023Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing...
INTRODUCTION
Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD.
METHODS
Fecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.
RESULTS
For alpha diversity, Faith's phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray-Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini-Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of group and lower relative abundance of .
DISCUSSION AND CONCLUSION
group reportedly includes pro-inflammatory bacteria. In contrast, suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of in parallel with increased abundance of group might be a susceptibility factor for KD.
Topics: Male; Child; Humans; Child, Preschool; Gastrointestinal Microbiome; Dysbiosis; RNA, Ribosomal, 16S; Mucocutaneous Lymph Node Syndrome; Phylogeny; Acute Disease; Ruminococcus
PubMed: 38022552
DOI: 10.3389/fimmu.2023.1268453 -
Microorganisms Aug 2023Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community... (Review)
Review
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the . Twenty-four studies were eligible. We identified strong evidence of two microbial markers and for ADA vs. CRC, and nine microbial markers -Lachnoclostridium, -Ruminococcus, spp., , Enterobacteriaceae, spp., Bacteroides, -, spp.-, , and for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
PubMed: 37630597
DOI: 10.3390/microorganisms11082037 -
BMC Microbiology Oct 2023The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and...
BACKGROUND
The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.
METHODS
We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites.
RESULTS
An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP.
CONCLUSIONS
Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.
Topics: Humans; Female; Pregnancy; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Feces; Bile Acids and Salts; Hypoxanthines
PubMed: 37784030
DOI: 10.1186/s12866-023-02983-x -
Cancer Medicine Jul 2023Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC...
BACKGROUND
Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC pathogenesis and progression, but the details remain unclear.
METHODS
We enrolled a cohort of 50 CRC patients and 52 healthy controls from an East China population. Taxonomic and functional analysis of the fecal microbiota were performed using 16S rDNA (50 + 52 samples) and shotgun metagenomic sequencing (8 + 6 samples), respectively, with particular attention paid to gut-colonized oral bacteria.
RESULTS AND CONCLUSIONS
The results showed more detected bacterial species but lower species evenness within the samples from CRC patients. To determine the specific bacteria enriched in each group, we analyzed their possible protective, carcinogenic, or opportunistic roles in the CRC process. Among the ectopic oral bacteria, we observed a significant increase in the abundance of Fusobacterium and decreased abundance of Prevotella and Ruminococcus in the CRC group. Main differences in the functional composition of these two groups were related to energy metabolism and biosynthesis, especially the glycolytic pathway. Furthermore, we validated the colonization of Fusobacterium nucleatum subsp. animalis within CRC tissues and studied its impact on the host intestinal epithelium and tumor cells. With high selectivity for cancerous tissues, this subspecies promoted CRC cell proliferation and induced potential DNA damage.
Topics: Humans; Gastrointestinal Microbiome; Colorectal Neoplasms; Bacteria; Microbiota; Carcinogenesis
PubMed: 37260140
DOI: 10.1002/cam4.6194 -
Frontiers in Microbiology 2024This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.
BACKGROUND
This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.
METHODS
We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed.
RESULTS
A positive correlation was observed between and the risk of osteoporosis, while showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the was significantly reduced, while the abundance of was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors.
CONCLUSION
and may regulate the development of osteoporosis through the microbiota-gut-bone axis.
PubMed: 38835486
DOI: 10.3389/fmicb.2024.1373013 -
Frontiers in Immunology 2023Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver...
INTRODUCTION
Metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as an increasingly recognized problem among people living with HIV (PLWH). The gut-liver axis is considered to be strongly implicated in the pathogenesis of MASLD. We aimed to characterize the gut microbiota composition in PLWH and MASLD and compare it with that of two control groups: PLWH without MASLD and individuals with MASLD without HIV infection.
METHODS
We collected clinical data and stool samples from participants. Bacterial 16S rRNA genes were amplified, sequenced, and clustered into operational taxonomic unit. Alpha diversity was studied by Shannon and Simpson indexes. To study how different the gut microbiota composition is between the different groups, beta diversity estimation was evaluated by principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity. To further analyze differences in microbiome composition we performed a linear discriminant analysis (LDA) effect size (LEfSe).
RESULTS
We included 30 HIVMASLD, 30 HIVMASLD and 20 HIVMASLD participants. Major butyrate producers, including , , and dominated the microbiota in all three groups. Shannon's and Simpson's diversity metrics were higher among MASLD individuals (Kruskal-Wallis p = 0.047). Beta diversity analysis showed distinct clustering in MASLD, with MASLD participants overlapping regardless of HIV status (ADONIS significance <0.001). MASLD was associated with increased homogeneity across individuals, in contrast to that observed in the HIV+NAFDL- group, in which the dispersion was higher (Permanova test, p value <0.001; ANOSIM, p value <0.001). MASLD but not HIV determined a different microbiota structure (HIV vs. HIVMASLD, q-value = 0.002; HIVMASLD vs. HIVMASLD, q-value = 0.930; and HIVMASLD vs. HIVMASLD, q-value < 0.001). The most abundant genera in MASLD- were , and . In contrast, the most enriched genera in MASLD+ were , and
CONCLUSIONS
We found a microbiome signature linked to MASLD, which had a greater influence on the overall structure of the gut microbiota than HIV status alone.
Topics: Humans; HIV Infections; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Metabolic Diseases; Clostridiales; Fatty Liver
PubMed: 38162648
DOI: 10.3389/fimmu.2023.1297378 -
European Journal of Cancer (Oxford,... Sep 2023Cyclin-dependent kinase (CDK)4/6-inhibitors with endocrine therapy represent the standard of treatment of hormone receptor-positive(HR+)/human epidermal growth factor...
BACKGROUND
Cyclin-dependent kinase (CDK)4/6-inhibitors with endocrine therapy represent the standard of treatment of hormone receptor-positive(HR+)/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Gut microbiota seems to predict treatment response in several tumour types, being directly implied in chemotherapy resistance and development of adverse effects. No evidence is available on gut microbiota impact on efficacy of HR+ breast cancer treatment.
PATIENTS AND METHODS
We assessed the potential association among faecal microbiota and therapeutic efficacy of CDK4/6-inhibitors on 14 MBC patients classified as responders (R) and non-responders (NR) according to progression-free survival. A stool sample was collected at baseline and V3-V4 16S targeted sequencing was employed to assess its bacterial composition. Statistical associations with R and NR were studied.
RESULTS
No significant differences were observed between R and NR in terms of α-/β-diversity at the phylum and species level. Machine-learning (ML) algorithms evidenced four bacterial species as a discriminant for R (Bifidobacterium longum, Ruminococcus callidus) and NR (Clostridium innocuum, Schaalia odontolytica), and an area under curve (AUC) of 0.946 after Random Forest modelling. Network analysis evidenced two major clusters of bacterial species, named Species Interacting Groups (SIG)1-2, with SIG1 harbouring 75% of NR-related bacterial species, and SIG2 regrouping 76% of R-related species (p < 0.001). Cross-correlations among several patients' circulating immune cells or biomarkers and bacterial species' relative abundances showed associations with potential prognostic implications.
CONCLUSIONS
Our results provide initial insights into the gut microbiota involvement in sensitivity and/or resistance to CDK4/6-inhibitors + endocrine therapy in MBC. If confirmed in larger trials, several microbiota manipulation strategies might be hypothesised to improve response to CDK4/6-inhibitors.
Topics: Humans; Female; Breast Neoplasms; Cross-Sectional Studies; Prospective Studies; Progression-Free Survival; Receptor, ErbB-2; Microbiota; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Cyclin-Dependent Kinase 4
PubMed: 37454444
DOI: 10.1016/j.ejca.2023.112948 -
Internal and Emergency Medicine Aug 2023This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases... (Review)
Review
This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases involving the IL-17 and NF-κB signaling pathways. Inflammatory cytokines including TNF-α and Th17 cells in CD patients can induce activation of the ERK1/2, NF-κB and Bcl-2 pathways. Hub genes are involved in the generation of cancer stem cells (CSCs) and are related to inflammatory mediators, including CXCL8, IL1-β and PTGS2, which promote inflammation and breast cancer growth, metastasis, and development. CD activity is highly associated with altered intestinal microbiota processes, including secretion of complex glucose polysaccharides by Ruminococcus gnavus colonies; furthermore, γ-proteobacteria and Clostridium are associated with CD recurrence and active CD, while Ruminococcaceae, Faecococcus and Vibrio desulfuris are associated with CD remission. Intestinal microbiota disorder promotes breast cancer occurrence and development. Bacteroides fragilis can produce toxins that induce breast epithelial hyperplasia and breast cancer growth and metastasis. Gut microbiota regulation can also improve chemotherapy and immunotherapy efficacy in breast cancer treatment. Intestinal inflammation can affects the brain through the brain-gut axis, which activates the hypothalamic‒pituitary‒adrenal (HPA) axis to induce anxiety and depression in patients; these effects can inhibit the antitumor immune responses of the immune system and promote breast cancer occurrence in patients with CD. There are few studies on the treatment of patients with CD concomitant with breast cancer, but published studies show three main strategies: new biological agents combined with breast cancer treatment methods, intestinal fecal bacteria transplantation, and dietary treatment.
Topics: Humans; Female; Crohn Disease; NF-kappa B; Breast Neoplasms; Intestinal Mucosa; Neoplasm Recurrence, Local; Inflammation
PubMed: 37138170
DOI: 10.1007/s11739-023-03281-0