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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 -
Gut Microbes 2022Colonic luminal aromatic amines have been historically considered to be derived from dietary source, especially fermented foods; however, recent studies indicate that...
Colonic luminal aromatic amines have been historically considered to be derived from dietary source, especially fermented foods; however, recent studies indicate that the gut microbiota serves as an alternative source of these amines. Herein, we show that five prominent genera of Firmicutes , and ) have the ability to abundantly produce aromatic amines through the action of aromatic amino acid decarboxylase (AADC). cultivation of human fecal samples revealed that a significant positive correlation between copy number of and phenylethylamine (PEA) production. Furthermore, using genetically engineered -colonized BALB/cCrSlc mouse model, we showed that the gut bacterial stimulates the production of colonic serotonin, which is reportedly involved in osteoporosis and irritable bowel syndrome. Finally, we showed that human AADC inhibitors carbidopa and benserazide inhibit PEA production in .
Topics: Animals; Aromatic-L-Amino-Acid Decarboxylases; Benserazide; Carbidopa; Gastrointestinal Microbiome; Humans; Mice; Phenethylamines; Serotonin
PubMed: 36217238
DOI: 10.1080/19490976.2022.2128605 -
Microbial Genomics Jul 2023is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being....
is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of . We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of was 42.73±0.33 mol%, and the mean genome size was 3.46±0.34 Mbp. Genome-wide evolutionary analysis revealed genomes were divided into three major phylogenetic clusters. Pan-core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74 % (1051/28 072), 1.75 % (491/28 072), 9.88 % (2774/28 072) and 84.63 % (23 756/28 072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are (tetracycline-resistance gene, present in 75 strains) and (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of . This study provides new insights for understanding the genomic features and health relevance of , and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.
Topics: Adult; Animals; Humans; Ruminococcus; Phylogeny; Clostridiales; Genomics
PubMed: 37486746
DOI: 10.1099/mgen.0.001071 -
Gut Microbes 2022The utilization of dietary cellulose by resident bacteria in the large intestine of mammals, both herbivores and omnivores (including humans), has been a subject of... (Review)
Review
The utilization of dietary cellulose by resident bacteria in the large intestine of mammals, both herbivores and omnivores (including humans), has been a subject of interest since the nineteenth century. Cellulolytic bacteria are key participants in this breakdown process of cellulose, which is otherwise indigestible by the host. They critically contribute to host nutrition and health through the production of short-chain fatty acids, in addition to maintaining the balance of intestinal microbiota. Despite this key role, cellulolytic bacteria have not been well studied. In this review, we first retrace the history of the discovery of cellulolytic bacteria in the large intestine. We then focus on the current knowledge of cellulolytic bacteria isolated from the large intestine of various animal species and humans and discuss the methods used for isolating these bacteria. Moreover, we summarize the enzymes and the mechanisms involved in cellulose degradation. Finally, we present the contribution of these bacteria to the host.
Topics: Animals; Bacteria; Cellulose; Gastrointestinal Microbiome; Humans; Intestine, Large; Mammals
PubMed: 35184689
DOI: 10.1080/19490976.2022.2031694 -
BMC Microbiology Apr 2024Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional... (Meta-Analysis)
Meta-Analysis
Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.
Topics: Humans; Gastrointestinal Microbiome; Metagenome; Obesity; Bacteria; Feces; Clostridiales; Akkermansia
PubMed: 38580930
DOI: 10.1186/s12866-024-03278-5 -
Microbiology (Reading, England) Aug 2023is a human gut symbiont, part of the infant and adult gut microbiota and associated with intestinal and extra-intestinal disorders. mechanisms of adaptation to the gut...
is a human gut symbiont, part of the infant and adult gut microbiota and associated with intestinal and extra-intestinal disorders. mechanisms of adaptation to the gut are strain-specific and underpinned by the capacity of strains to utilize mucin and dietary glycans and produce bacteriocins and adhesins. Several potential mediators underpinning the association between strains and diseases have been identified, including the capacity to elicit a pro- or anti-inflammatory host response and modulate host metabolism, secondary bile acids and tryptophan metabolic pathways. Based on increasing evidence from metagenomics studies in humans and functional investigations and in mouse models, is emerging as a main player in influencing health and disease outcomes from infants to the elderly.
Topics: Humans; Ruminococcus; Gastrointestinal Microbiome; Symbiosis
PubMed: 37622435
DOI: 10.1099/mic.0.001383 -
BMC Cancer Jul 2023Colorectal cancer (CRC) is a heterogeneous disease, with subtypes that have different clinical behaviours and subsequent prognoses. There is a growing body of evidence...
BACKGROUND
Colorectal cancer (CRC) is a heterogeneous disease, with subtypes that have different clinical behaviours and subsequent prognoses. There is a growing body of evidence suggesting that right-sided colorectal cancer (RCC) and left-sided colorectal cancer (LCC) also differ in treatment success and patient outcomes. Biomarkers that differentiate between RCC and LCC are not well-established. Here, we apply random forest (RF) machine learning methods to identify genomic or microbial biomarkers that differentiate RCC and LCC.
METHODS
RNA-seq expression data for 58,677 coding and non-coding human genes and count data for 28,557 human unmapped reads were obtained from 308 patient CRC tumour samples. We created three RF models for datasets of human genes-only, microbes-only, and genes-and-microbes combined. We used a permutation test to identify features of significant importance. Finally, we used differential expression (DE) and paired Wilcoxon-rank sum tests to associate features with a particular side.
RESULTS
RF model accuracy scores were 90%, 70%, and 87% with area under curve (AUC) of 0.9, 0.76, and 0.89 for the human genomic, microbial, and combined feature sets, respectively. 15 features were identified as significant in the model of genes-only, 54 microbes in the model of microbes-only, and 28 genes and 18 microbes in the model with genes-and-microbes combined. PRAC1 expression was the most important feature for differentiating RCC and LCC in the genes-only model, with HOXB13, SPAG16, HOXC4, and RNLS also playing a role. Ruminococcus gnavus and Clostridium acetireducens were the most important in the microbial-only model. MYOM3, HOXC4, Coprococcus eutactus, PRAC1, lncRNA AC012531.25, Ruminococcus gnavus, RNLS, HOXC6, SPAG16 and Fusobacterium nucleatum were most important in the combined model.
CONCLUSIONS
Many of the identified genes and microbes among all models have previously established associations with CRC. However, the ability of RF models to account for inter-feature relationships within the underlying decision trees may yield a more sensitive and biologically interconnected set of genomic and microbial biomarkers.
Topics: Colorectal Neoplasms; Humans; Random Forest; Machine Learning; Microbiota; Genetic Markers; Male; Female; Adult; Middle Aged; Aged; Aged, 80 and over
PubMed: 37434131
DOI: 10.1186/s12885-023-10848-9 -
Pharmacological Research Mar 2023The gut microbiome is closely shaped by host genetic and dietary factors to regulate metabolic health and disease. However, the signaling mechanisms underlying such...
The gut microbiome is closely shaped by host genetic and dietary factors to regulate metabolic health and disease. However, the signaling mechanisms underlying such interactions have been largely unclear. Here we identify G protein-coupled receptor 35 (Gpr35) as a regulator of gut microbial ecology and the susceptibility to obesity and hepatic steatosis in mice. Both global and intestinal epithelia specific ablation of Gpr35 aggravated high-fat diet (HFD)-induced metabolic disturbance and hepatic steatosis in mice. Gpr35 deficiency induced a remarkable loss of goblet cells and an extensive remodeling of the gut microbiome, featuring enrichment of the Bacteroides and Ruminococcus genera. Antibiotics treatment and co-housing alleviated the metabolic disturbance markers in Gpr35 deficient mice. Spatiotemporal profiling and mono-colonization screening revealed that Ruminococcus gnavus synergized with HFD to promote hepatic steatosis possibly via tryptophan and phenylalanine pathway metabolites. Our results provide mechanistic insights into a genetic-diet-microbe interplay that dictates susceptibility to metabolic disorder.
Topics: Mice; Animals; Gastrointestinal Microbiome; Fatty Liver; Receptors, G-Protein-Coupled; Obesity; Diet, High-Fat; Mice, Inbred C57BL; Liver
PubMed: 36758734
DOI: 10.1016/j.phrs.2023.106690 -
Frontiers in Cellular and Infection... 2023Cervical cancer (CC) is the fourth most frequent malignancy among women worldwide, and its prevention and treatment are evolving rapidly. The gut microbiota has been...
Cervical cancer (CC) is the fourth most frequent malignancy among women worldwide, and its prevention and treatment are evolving rapidly. The gut microbiota has been reported to play a crucial role both in the preservation of homeostasis and the development of cervical cancer. In this study, we collected fecal samples to investigate the microbial signatures in cervical cancer patients compared with healthy controls using 16S rRNA sequencing analysis and metagenomic next-generation sequencing (mNGS) testing. Our findings demonstrated a substantial difference in the gut microbiota composition of cervical cancer patients and healthy controls. The disease and stage were most significantly negatively correlated with , which might be considered a potential clinically relevant biomarker. Functions of differential microbiomes were also analyzed, indicating significant differences in metabolisms and biosynthesis between the two groups. These findings demonstrate that patients with cervical cancer have certain species of gut microbiota that are exclusive to them and particular species have the potential to be used in the prognosis of cervical cancer.
Topics: Humans; Female; Uterine Cervical Neoplasms; RNA, Ribosomal, 16S; Microbiota; Gastrointestinal Microbiome; Feces
PubMed: 36909733
DOI: 10.3389/fcimb.2023.1145950 -
Frontiers in Veterinary Science 2021Ducks with the same genetic background vary greatly in their adiposity phenotypes. The gut microbiota plays an essential role in host physiological development and...
Ducks with the same genetic background vary greatly in their adiposity phenotypes. The gut microbiota plays an essential role in host physiological development and metabolism including fat deposition. However, the association of the gut microbiota with the lipogenic phenotype of ducks remains unknown. In this study, we investigated the cecal microbiota of adult Muscovy ducks and the correlation of the cecal microbiota with fat phenotypes. A total of 200 Muscovy ducks were selected from a population of 5,000 Muscovy ducks to record their abdominal fat weight and collect their cecal contents after being slaughtered and defeathered. The cecal contents were subjective to DNA isolation and 16S rRNA gene sequencing. The results were sorted according to the percentage of abdominal fat and the top 20% ( = 40) and the bottom 20% ( = 40) were set as the high and low groups, respectively. Our results indicated that in the cecum of Muscovy ducks, Bacteroidetes, Firmicutes, and Fusobacteria were the predominant phyla while , and were the top 4 dominant genera. Abdominal fat weight (18.57~138.10 g) and percentage of abdominal fat (1.02~27.12%) were significantly correlated ( = 0.92, < 0.001). Although the lipogenic phenotypes of ducks had a significant difference ( < 0.05), the α-diversities of the high and low groups were not significantly different ( > 0.05). Nevertheless, after random forest analysis, we identified two genera, and , that were significantly associated with fat deposition in Muscovy ducks. In addition, the abundances of and gave a significantly negative and positive association with abdominal fat weight, respectively ( < 0.05). Ducks with a low level of exhibited a tendency toward a high percentage of abdominal fat ( < 0.01), while the percentage of abdominal fat in ducks with high abundance tended to be higher than that in ducks with low abundance ( < 0.01). These findings could provide the basic data on the cecal microbiota in Muscovy ducks as well as a theoretical foundation to limit the fat deposition by modulating the gut microbiota in the duck industry.
PubMed: 33869315
DOI: 10.3389/fvets.2021.609348