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Frontiers in Cellular and Infection... 2023In recent years, observational studies have provided evidence supporting a potential association between autism spectrum disorder (ASD) and gut microbiota. However, the...
BACKGROUND
In recent years, observational studies have provided evidence supporting a potential association between autism spectrum disorder (ASD) and gut microbiota. However, the causal effect of gut microbiota on ASD remains unknown.
METHODS
We identified the summary statistics of 206 gut microbiota from the MiBioGen study, and ASD data were obtained from the latest Psychiatric Genomics Consortium Genome-Wide Association Study (GWAS). We then performed Mendelian randomization (MR) to determine a causal relationship between the gut microbiota and ASD using the inverse variance weighted (IVW) method, simple mode, MR-Egger, weighted median, and weighted model. Furthermore, we used Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis to identify heterogeneity and pleiotropy. Moreover, the Benjamin-Hochberg approach (FDR) was employed to assess the strength of the connection between exposure and outcome. We performed reverse MR analysis on the gut microbiota that were found to be causally associated with ASD in the forward MR analysis to examine the causal relationships. The enrichment analyses were used to analyze the biological function at last.
RESULTS
Based on the results of IVW results, genetically predicted and had a possible positive association with ASD (IVW OR=1.14, 95% CI: 1.00-1.29, =3.7×10), four gut microbiota with a potential protective effect on ASD: (OR=0.81, 95% CI: 0.69-0.96, =1.4×10), (OR=0.81, 95% CI: 0.69-0.96, =1.5×10), (OR=0.83, 95% CI: 0.70-0.98, =2.8×10), and (OR=0.82, 95% CI: 0.68-0.99, =3.6×10). After FDR multiple-testing correction we further observed that there were two gut microbiota still have significant relationship with ASD: (IVW OR=1.24; 95% CI: 1.09-1.40, =9.2×10) was strongly positively correlated with ASD and (IVW OR=0.78, 95% CI: 0.67-0.89, =6.9×10) was strongly negatively correlated with ASD. The sensitivity analysis excluded the influence of heterogeneity and horizontal pleiotropy.
CONCLUSION
Our findings reveal a causal association between several gut microbiomes and ASD. These results deepen our comprehension of the role of gut microbiota in ASD's pathology, providing the foothold for novel ideas and theoretical frameworks to prevent and treat this patient population in the future.
Topics: Humans; Gastrointestinal Microbiome; Autism Spectrum Disorder; Genome-Wide Association Study; Mendelian Randomization Analysis; Bacteroidetes
PubMed: 38156319
DOI: 10.3389/fcimb.2023.1267721 -
Archives of Gerontology and Geriatrics Oct 2023The relationship among gut microbiota, sarcopenia components, and influencing factors in female sarcopenic patients has been poorly investigated.
BACKGROUND
The relationship among gut microbiota, sarcopenia components, and influencing factors in female sarcopenic patients has been poorly investigated.
METHODS
Female participants completed questionnaires of physical activity and dietary frequency and were assessed for the presence of sarcopenia by the Asian Working Group of Sarcopenia 2019 (AWGS 2019) criteria. Fecal samples were collected from 17 sarcopenia and 30 non-sarcopenia subjects for 16S sequencing and short chain fatty acid (SCFA) detection.
RESULTS
The prevalence of sarcopenia was 19.20% among 276 participants. The dietary protein, fat, dietary fiber, vitamin B1, niacin, vitamin E, phosphorus, magnesium, iron, zinc, and cooper intake of sarcopenia were all remarkably low. In addition, the richness of gut microbiota (Chao1 and ACE indexes) was considerably reduced in sarcopenic patients, and the sarcopenic gut microbiota and its metabolite were decreased in Firmicutes/Bacteroidetes, Agathobacter, Dorea and Butyrate and were enriched in Shigella and Bacteroides. Correlation analysis showed that Agathobacter and Acetate were positively correlated with grip strength and gait speed, respectively, and Bifidobacterium was negatively correlated with grip strength and appendicular skeletal muscle index (ASMI). Moreover, the protein intake was positively related to Bifidobacterium.
CONCLUSIONS
This cross-sectional study revealed the alterations of gut microbiota composition, SCFA, and nutrient intake in women with sarcopenia and their relation to sarcopenic components. These results provide insights into further studies on the role of nutrition and gut microbiota in sarcopenia and its use as a therapeutic approach.
Topics: Humans; Female; Aged; Sarcopenia; Gastrointestinal Microbiome; Independent Living; Cross-Sectional Studies; East Asian People; Eating
PubMed: 37216814
DOI: 10.1016/j.archger.2023.105063 -
Digestion 2023Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the... (Observational Study)
Observational Study
BACKGROUND AND AIM
Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome.
METHODS
We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis.
RESULTS
Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group.
CONCLUSION
Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs.
Topics: Humans; Gastrointestinal Microbiome; Dysbiosis; Diarrhea; Bacteria; Antineoplastic Agents; RNA, Ribosomal, 16S
PubMed: 37231829
DOI: 10.1159/000528282 -
Genome Biology Oct 2023The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to...
BACKGROUND
The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.
RESULTS
Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.
CONCLUSION
This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.
Topics: Humans; Metagenome; Gastrointestinal Microbiome; Kidney Failure, Chronic; Microbiota; Renal Insufficiency, Chronic; Feces; Clostridiales
PubMed: 37828586
DOI: 10.1186/s13059-023-03056-y -
Journal of Gastrointestinal and Liver... Sep 2023Traditional cardiovascular risk factors are established predictors of heart failure (HF). However, the human gut microbiota is suggested to potentially interact with the...
BACKGROUND AND AIMS
Traditional cardiovascular risk factors are established predictors of heart failure (HF). However, the human gut microbiota is suggested to potentially interact with the cardiovascular system through the "gut-heart axis", which induces inflammation and contributes to HF pathogenesis. This systematic review aims to confirm the interconnection between the gut microbiome in HF patients.
METHODS
Peer-reviewed human studies comparing the gut microbiota profile in adult patients with HF and healthy controls (HCs) up to April 18, 2022, were searched in Ovid MEDLINE, Ovid EMBASE, SCOPUS, and the Cochrane Library. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS
A total of nine studies, including 317 HF patients and 510 HCs, were included in the review. Decreased gut microbiota richness and similar microbial diversity (alpha diversity), and significantly different gut microbiota composition (beta diversity) were observed between HF patients and HCs. In comparison to HCs, HF patients had a greater abundance of Actinobacteria, Proteobacteria, and Synergistetes phyla; Enterococcus, Escherichia, Klebsiella, Lactobacillus, Streptococcus, and Veilonella genera and Ruminococcus gnavus, Streptococcus sp., and Veilonella sp. species. In contrast, there was decreased abundance of Firmicutes phylum; Blautia, Eubacterium, Faecalibacterium, and Lachnospiraceae FCS020 genera; and Dorea longicatena, Eubacterium rectale, Faecalibacterium prausnitzii, Oscillibacter sp., and Sutterella wadsworthensis species in HF patients.
CONCLUSIONS
Gut microbiota diversity, richness, and composition in HF patients differ significantly from the healthy population. Overall, short-chain fatty acid (SCFA)-producing gut microbiota was depleted in HF patients. However, different underlying comorbidities, environments, lifestyles, and dietary choices could affect gut microbiota heterogeneity.
Topics: Adult; Humans; Gastrointestinal Microbiome; Diet; Bacteria; Heart Failure; Inflammation
PubMed: 37774217
DOI: 10.15403/jgld-4779 -
Nature Communications Apr 2023Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported,...
Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
Topics: Male; Humans; Female; Absorptiometry, Photon; Body Composition; Bone Density; Sarcopenia; Osteoporosis
PubMed: 37080991
DOI: 10.1038/s41467-023-37978-9 -
International Journal of Molecular... Jan 2023Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and...
Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut-brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active metabolic pathways, which might be implicated in the (non-)motor symptoms, was investigated. We performed both metagenomic and 16S rRNA sequencing on the stool samples of three subtypes of dystonia (27 cervical dystonia, 20 dopa-responsive dystonia and 24 myoclonus-dystonia patients) and 25 controls. While microbiome alpha and beta diversity was not different between dystonia patients and controls, dystonia patients had higher abundances of and , and a lower abundance of compared to controls. For those with dystonia, non-motor symptoms and the levels of neurotransmitters in plasma explained the variance in the gut microbiome composition. Several neuro-active metabolic pathways, especially tryptophan degradation, were less abundant in the dystonia patients compared to controls. This suggest that the gut-brain axis might be involved in the pathophysiology of dystonia. Further studies are necessary to confirm our preliminary findings.
Topics: Humans; Dystonia; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Mental Disorders; Dystonic Disorders; Dyskinesias
PubMed: 36768705
DOI: 10.3390/ijms24032383 -
Clinical Cancer Research : An Official... Mar 2021The gut microbiome is involved in antitumor immunotherapy and chemotherapy responses; however, evidence-based research on the role of gut microbiome in predicting...
PURPOSE
The gut microbiome is involved in antitumor immunotherapy and chemotherapy responses; however, evidence-based research on the role of gut microbiome in predicting response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) remains scarce. This prospective, longitudinal study aimed to evaluate the feasibility of the gut microbiome in predicting nCRT responses.
EXPERIMENTAL DESIGN
We collected 167 fecal samples from 84 patients with LARC before and after nCRT and 31 specimens from healthy individuals for 16S rRNA sequencing. Patients were divided into responders and nonresponders according to pathologic response to nCRT. After identifying microbial biomarkers related to nCRT responses, we constructed a random forest classifier for nCRT response prediction of a training cohort of baseline samples from 37 patients and validated the classifier in another cohort of 47 patients.
RESULTS
We observed significant microbiome alterations represented by a decrease in LARC-related pathogens and an increase in and during nCRT. Furthermore, a prominent microbiota difference between responders and nonresponders was noticed in the baseline samples. Microbes related with butyrate production, including , and , were overrepresented in responders, whereas and were overrepresented in nonresponders. Ten biomarkers were selected for the response-prediction classifier, including , and , which yielded an area under the curve value of 93.57% [95% confidence interval (CI), 85.76%-100%] in the training cohort and 73.53% (95% CI, 58.96%-88.11%) in the validation cohort.
CONCLUSIONS
The gut microbiome offers novel potential biomarkers for predicting nCRT responses, which has important manifestations in the clinical management of these patients.
Topics: Bacteria; Feasibility Studies; Female; Follow-Up Studies; Gastrointestinal Microbiome; Humans; Longitudinal Studies; Male; Middle Aged; Neoadjuvant Therapy; Prognosis; Prospective Studies; RNA, Ribosomal, 16S; Rectal Neoplasms; Survival Rate
PubMed: 33298472
DOI: 10.1158/1078-0432.CCR-20-3445 -
Clinical Nutrition Research Jul 2021Recently several studies have attempted to investigate the association between vitamin D and microbiota. However, studies have reported inconsistent results. This... (Review)
Review
Recently several studies have attempted to investigate the association between vitamin D and microbiota. However, studies have reported inconsistent results. This narrative review aimed to investigate the potential association between vitamin D and microbiota population in the gut by pooling together the results from observational studies and clinical trials. We considered animal and human studies in this field. Several studies have shown the correlation of vitamin D deficiency with microbiota. Furthermore, interventional studies were emerging that vitamin D change the microbiota composition in which leads to an increase in beneficial bacteria, such as , , , and while decreases in . Vitamin D could change the microbiota toward decreasing in and increasing in . At genera level, vitamin D may connect to some genera of family (e.g., , , , and ). It seems that adequate level of vitamin D is an important factor in improving the composition of the gut microbiota. More studies are needed to confirm possible underling mechanisms.
PubMed: 34386438
DOI: 10.7762/cnr.2021.10.3.181 -
Journal of Paediatrics and Child Health Mar 2023
PubMed: 36738441
DOI: 10.1111/jpc.16360