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Renal Failure Dec 2024Research has showcased a correlation between disruptions in gut microbiota and primary membranous nephropathy (pMN), giving rise to the concept of the 'gut-kidney axis'....
BACKGROUND
Research has showcased a correlation between disruptions in gut microbiota and primary membranous nephropathy (pMN), giving rise to the concept of the 'gut-kidney axis'. However, the precise relationship between gut microbiota and pMN remains elusive. Hence, this study endeavors to investigate whether a causal relationship exists between gut microbiota and pMN utilizing Mendelian randomization (MR) analysis.
METHODS
The primary method employed for MR analysis is the inverse variance weighting method, supplemented by MR-Egger and the weighted median method, to infer causality. This approach was validated within the pMN cohort across two distinct populations.
RESULTS
At the species level, the abundance of and was negatively correlated with the risk of pMN. Conversely, pMN was positively associated with abundance at the class level, abundance at the family level, and abundance at the genus level. Specifically, at the species level, pMN was positively correlated with the abundance of , , and
CONCLUSION
These findings lay the groundwork for future research exploring the interplay between pMN and the gut microbiota, with substantial implications for the prevention and treatment of pMN and its associated complications.
Topics: Humans; Mendelian Randomization Analysis; Glomerulonephritis, Membranous; Gastrointestinal Microbiome; Male; Female; Middle Aged; Bifidobacterium bifidum; Adult
PubMed: 38770992
DOI: 10.1080/0886022X.2024.2349136 -
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 -
Experimental and Therapeutic Medicine Jun 2024Multiple myeloma (MM) is a plasma cell clonal disease and these plasma cells can survive in the gut. The intestinal microbiota is a complex ecosystem and its dysfunction...
Multiple myeloma (MM) is a plasma cell clonal disease and these plasma cells can survive in the gut. The intestinal microbiota is a complex ecosystem and its dysfunction can release persistent stimulus signals that trigger genetic mutations and clonal evolution in the gut. The present study analyzed the intestinal microbiota in fecal samples of MM patients in high-altitude and cold regions of China using 16s rRNA sequencing and analyzed significantly enriched species at the phylum and genus levels. Although no significant difference in the alpha diversity was observed between the MM and control groups, a significant difference was noted in the beta diversity. A total of 15 significant differential bacteria at the genus level were found between the two groups, among which , , and were significantly enriched in the MM group. The present study also constructed a disease diagnosis model using Random Forest analysis and verified its accuracy using receiver operating characteristic analysis. In addition, using correlation analysis, it demonstrated that the composition of the intestinal microbiota in patients with MM was associated with complement levels. Notably, the present study predicted that the signaling and metabolic pathways of the intestinal microbiota affected MM progression through Kyoto Encyclopedia of Genes and Genomes functional analysis. The present study provides a new approach for the prevention and treatment of MM, in which the intestinal microbiota may become a novel therapeutic target for MM.
PubMed: 38756900
DOI: 10.3892/etm.2024.12557 -
Pharmacological Research Jun 2024In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis....
In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in IPA group while in IPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant. Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis.
Topics: Humans; Male; Animals; Gastrointestinal Microbiome; Female; Middle Aged; Insulin Resistance; Indoles; Mice, Inbred C57BL; Metabolomics; Mice; Adult; Metabolic Syndrome; Comorbidity; Muscle, Skeletal; Multiomics
PubMed: 38734193
DOI: 10.1016/j.phrs.2024.107207 -
Nutrients Apr 2024Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in...
Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in school-age children have not been reported. School-age children were enrolled to conduct anthropometric measurements and serum zinc and serum inflammatory factors detection, and children were divided into a zinc deficiency group (ZD) and control group (CK) based on the results of serum zinc. Stool samples were collected to conduct metagenome, metabolome, and diversity analysis, and species composition analysis, functional annotation, and correlation analysis were conducted to further explore the function and composition of the gut flora and metabolites of children with zinc deficiency. Beta-diversity analysis revealed a significantly different gut microbial community composition between ZD and CK groups. For instance, the relative abundances of , , , sp000434735, and were more enriched in the ZD group, while probiotic bacteria showed the reverse trend. The functional profile of intestinal flora was also under the influence of zinc deficiency, as reflected by higher levels of various glycoside hydrolases in the ZD group. In addition, saccharin, the pro-inflammatory metabolites, and taurocholic acid, the potential factor inducing intestinal leakage, were higher in the ZD group. In conclusion, zinc deficiency may disturb the gut microbiome community and metabolic function profile of school-age children, potentially affecting human health.
Topics: Humans; Gastrointestinal Microbiome; Zinc; Child; Male; Female; Feces; Bacteria; Intestinal Mucosa; Metabolome; Intestines
PubMed: 38732540
DOI: 10.3390/nu16091289 -
Gut Microbes 2024Colorectal cancer (CRC), a malignant tumor worldwide, is associated with gut microbiota. The influence of gut microbe-derived metabolites on CRC has attracted a lot of...
Colorectal cancer (CRC), a malignant tumor worldwide, is associated with gut microbiota. The influence of gut microbe-derived metabolites on CRC has attracted a lot of attention. However, the role of immunity mediated by commensal microbiota-derived metabolites in tumorigenesis of CRC is not intensively explored. Here we monitored the gut microbial dysbiosis in CRC mouse model ( model) without dietary and pharmacological intervention, followed by characterized of metabolites enriched in CRC model mice. Profound changes of gut microbiome (bacteriome) were observed during intestinal disorders. Metabolomic profiling indicated that agmatine, derived from the gut bacteria and , could interact with Rnf128 to suppress the Rnf128-mediated ubiquitination of β-catenin to further upregulate the downstream targets of β-catenin including Cyclin D1, Lgr5, CD44 and C-myc, thus activating Wnt signaling. The activated Wnt signaling pathway promoted dysplasia of intestinal cells and inflammatory infiltration of lymphocytes via inducing the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) and downregulation of anti-inflammatory cytokine (IL-10), thereby contributing to colorectal carcinogenesis. Therefore, our study presented novel insights into the roles and mechanisms of gut microbiota in pathogenesis of CRC.
Topics: Animals; Gastrointestinal Microbiome; Colorectal Neoplasms; Mice; Carcinogenesis; Wnt Signaling Pathway; Inflammation; Bacteria; Mice, Inbred C57BL; beta Catenin; Dysbiosis; Humans; Disease Models, Animal; Cytokines; Symbiosis; Male
PubMed: 38706224
DOI: 10.1080/19490976.2024.2348441 -
Frontiers in Neuroscience 2024Aging is a complex, time-dependent biological process that involves a decline of overall function. Over the past decade, the field of intestinal microbiota associated...
INTRODUCTION
Aging is a complex, time-dependent biological process that involves a decline of overall function. Over the past decade, the field of intestinal microbiota associated with aging has received considerable attention. However, there is limited information surrounding microbiota-gut-brain axis (MGBA) to further reveal the mechanism of aging.
METHODS
In this study, locomotory function and sensory function were evaluated through a series of behavioral tests.Metabolic profiling were determined by using indirect calorimetry.16s rRNA sequence and targeted metabolomics analyses were performed to investigate alterations in the gut microbiota and fecal short-chain fatty acids (SCFAs). The serum cytokines were detected by a multiplex cytokine assay.The expression of proinflammatory factors were detected by western blotting.
RESULTS
Decreased locomotor activity, decreased pain sensitivity, and reduced respiratory metabolic profiling were observed in aged mice. High-throughput sequencing revealed that the levels of genus Lactobacillus and Dubosiella were reduced, and the levels of genus Alistipes and Bacteroides were increased in aged mice. Certain bacterial genus were directly associated with the decline of physiological behaviors in aged mice. Furthermore, the amount of fecal SCFAs in aged mice was decreased, accompanied by an upregulation in the circulating pro-inflammatory cytokines and increased expression of inflammatory factors in the brain.
DISCUSSION
Aging-induced microbial dysbiosis was closely related with the overall decline in behavior, which may attribute to the changes in metabolic products, e.g., SCFAs, caused by an alteration in the gut microbiota, leading to inflammaging and contributing to neurological deficits. Investigating the MGBA might provide a novel viewpoint to exploring the pathogenesis of aging and expanding appropriate therapeutic targets.
PubMed: 38699678
DOI: 10.3389/fnins.2024.1362239 -
Veterinary World Mar 2024Simiao Yong'an decoction (SYD) is a classic traditional Chinese medicine (TCM) prescription that has the effects of clearing heat, detoxifying, promoting blood...
BACKGROUND AND AIM
Simiao Yong'an decoction (SYD) is a classic traditional Chinese medicine (TCM) prescription that has the effects of clearing heat, detoxifying, promoting blood circulation, and relieving pain. In this study, we investigated the effect of SYD on the diversity of intestinal microbiota after fermentation by .
MATERIALS AND METHODS
SYD was fermented using . Female Sprague-Dawley rats were randomly divided into the following four groups with six rats in each group: Negative sample group (NS), water exaction non-fermentation group (WE), s group (BS), and fermentation liquid group (FL). All rats were orally administered for 14 days. High-throughput Illumina sequencing was used to analyze 16S rRNA expression in rat fecal samples.
RESULTS
A total of 2782 operational taxonomical units (OTUs) were identified in this study, and 634 OTUs were shared among all samples. Bacteroidetes (28.17%-53.20%) and Firmicutes (48.35%-67.83%) were the most abundant phyla identified among the four groups. The abundance of Escherichia and Alistipes was lower in the FL group than in the NS group, whereas the abundance of Bifidobacteria and Lactobacillus was increased in the FL group (p < 0.05). The abundance of Bifidobacterium was significantly upregulated in the FL group compared with the WE and BS groups (p < 0.05).
CONCLUSION
After fermentation, SYD had a significantly better effect than SYD or . SYD significantly promoted the growth of intestinal probiotics, inhibited the growth of pathogenic bacteria, and maintained the balance of intestinal microbiota in SD rats. This study provides new insights into the development and use of SYD.
PubMed: 38680148
DOI: 10.14202/vetworld.2024.712-719 -
Biomedicines Apr 2024In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates...
Complementary Therapeutic Effect of Fecal Microbiota Transplantation in Ulcerative Colitis after the Response to Anti-Tumor Necrosis Factor Alpha Agent Was Lost: A Case Report.
In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). , , , , , and , which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.
PubMed: 38672155
DOI: 10.3390/biomedicines12040800 -
Communications Biology Apr 2024Ethnicity 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...
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.
Topics: Adult; Female; Humans; Male; Bacteria; Bangladesh; Ethnicity; Feces; Gastrointestinal Microbiome; Indigenous Peoples; RNA, Ribosomal, 16S; South Asian People
PubMed: 38664512
DOI: 10.1038/s42003-024-06191-9