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Microbiome Aug 2023A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure.
RESULTS
Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota's resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting "responders" and "non-responders" independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities.
CONCLUSIONS
We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached. Video Abstract.
Topics: Humans; Microbiota; Gastrointestinal Microbiome; Biomarkers; Diet; Life Style
PubMed: 37553697
DOI: 10.1186/s40168-023-01604-z -
Microbiology Spectrum Sep 2023Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and...
Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and treating acute pancreatitis by affecting the host's metabolism. In this study, we followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease (before treatment, on the third day of treatment, and 1 month after discharge). We analyzed species composition and metabolic pathways' changes across the treatment phase, severity, and etiology. The diversity of the gut microbiome of patients with AP did not show much variation with treatment. In contrast, the metabolic functions of the gut microbiota, such as the essential chemical reactions that produce energy and maintain life, were partially reinstated after treatment. The severe AP (SAP) patients contained less beneficial bacteria (i.e., , and ) and weaker sugar degradation function than mild AP patients before treatment. Moreover, etiology was one of the drivers of gut microbiome composition and explained the 3.54% variation in species' relative abundance. The relative abundance of pathways related to lipid synthesis was higher in the gut of hyperlipidemia AP patients than in biliary AP patients. The composition and functional profiles of the gut microbiota reflect the severity and etiology of AP. Otherwise, we also identified bacterial species associated with SAP, i.e., sp 57_20 and , which have the potential to identify the SAP at an early stage. IMPORTANCE Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in the development and treatment of acute pancreatitis by affecting the host's metabolism. However, fewer studies acquired metagenomic sequencing data to associate species to functions intuitively and performed longitudinal analysis to explore how gut microbiota influences the development of AP. We followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease and studied the differences in intestinal flora under different severities and etiologies. We have two findings. First, the gut microbiota profile has the potential to identify the severity and etiology of AP at an early stage. Second, gut microbiota likely acts synergistically in the development of AP. This study provides a reference for characterizing the driver flora of severe AP to identify the severity of acute pancreatitis at an early stage.
PubMed: 37698429
DOI: 10.1128/spectrum.00829-23 -
Microbiology Spectrum May 2024Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites...
Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of , , and was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: and . Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. and may be involved in the degradation of indoles and derivatives. , , and may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that , , , and might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.
Topics: Humans; Feces; Esophageal Squamous Cell Carcinoma; Metabolomics; Gastrointestinal Microbiome; Esophageal Neoplasms; Male; Female; Middle Aged; Bacteria; RNA, Ribosomal, 16S; Biomarkers, Tumor; Aged; Adult
PubMed: 38497715
DOI: 10.1128/spectrum.04012-23 -
Frontiers in Cellular and Infection... 2023There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a...
BACKGROUND
There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a comprehensive understanding of gut microbiota disturbance in children with GERD through combined metagenomic and metabolomic analysis.
METHODS
30 children with GERD and 30 healthy controls (HCs) were continuously enrolled, and the demographic and clinical characteristics of the subjects were collected. First, 16S rRNA sequencing was used to evaluate differences in the gut microbiota between children with GERD and HC group, and 10 children with GERD and 10 children in the HC group were selected for metagenomic analysis. Nontargeted metabolomic analysis was performed using liquid chromatography/mass spectrometry (LC/MS), and metagenomic and metabolomic data were analyzed together.
RESULTS
There were significant differences in the gut microbiota diversity and composition between children with GERD and HCs. The dominant bacteria in children with GERD were Proteobacteria and Bacteroidota. At the species level, the top three core bacterial groups were , and . The main differential pathways were identified to be related to energy, amino acid, vitamin, carbohydrate and lipid metabolism. LC/MS detected 288 different metabolites in the positive and negative ion modes between children with GERD and HCs, which were mainly involved in arachidonic acid (AA), tyrosine, glutathione and caffeine metabolism.
CONCLUSION
This study provides new evidence of the pathogenesis of GERD. There are significant differences in the gut microbiota, metabolites and metabolic pathways between HCs and children with GERD, and the differences in metabolites are related to specific changes in bacterial abundance. In the future, GERD may be treated by targeting specific bacteria related to AA metabolism.
Topics: Humans; Child; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Metabolomics; Bacteria; Metagenomics; Gastroesophageal Reflux
PubMed: 37900308
DOI: 10.3389/fcimb.2023.1267192 -
Microbiome Feb 2024Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS...
Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS could not be absorbed after oral intake due to its polyanionic nature and large molecular weight. Gut microbiota has recently been proposed to play a pivotal role in the metabolism of drugs and nutrients. Nonetheless, how CS is degraded by the human gut microbiota has not been fully characterized. In the present study, we demonstrated that each human gut microbiota was characterized with a unique capability for CS degradation. Degradation and fermentation of CS by the human gut microbiota produced significant amounts of unsaturated CS oligosaccharides (CSOSs) and short-chain fatty acids. To uncover which microbes were responsible for CS degradation, we isolated a total of 586 bacterial strains with a potential CS-degrading capability from 23 human fecal samples. Bacteroides salyersiae was a potent species for CS degradation in the human gut microbiota and produced the highest amount of CSOSs as compared to other well-recognized CS-degraders, including Bacteroides finegoldii, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, and Bacteroides ovatus. Genomic analysis suggested that B. salyersiae was armed with multiple carbohydrate-active enzymes that could potentially degrade CS into CSOSs. By using a spent medium assay, we further demonstrated that the unsaturated tetrasaccharide (udp4) produced by the primary degrader B. salyersiae could serve as a "public goods" molecule for the growth of Bacteroides stercoris, a secondary CS-degrader that was proficient at fermenting CSOSs but not CS. Taken together, our study provides insights into the metabolism of CS by the human gut microbiota, which has promising implications for the development of medical and nutritional therapies for osteoarthritis. Video Abstract.
Topics: Humans; Chondroitin Sulfates; Gastrointestinal Microbiome; Oligosaccharides; Osteoarthritis; Bacteroides
PubMed: 38419055
DOI: 10.1186/s40168-024-01768-2 -
Frontiers in Microbiology 2023The association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown.
BACKGROUND
The association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown.
METHODS
Fecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins.
RESULTS
Non-responders harbored higher microbiome α-diversity but lower β-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, β-diversity has also been observed between these two groups. Specifically, , and were more abundant among responders, whereas and were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases.
CONCLUSION
We revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets.
PubMed: 37564290
DOI: 10.3389/fmicb.2023.1165360 -
Cancers Apr 2024The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies...
The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder ( = 28) and non-responder ( = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of and was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.
PubMed: 38730627
DOI: 10.3390/cancers16091675 -
BioRxiv : the Preprint Server For... Mar 2024The prototypic crAssphage () is one of the most abundant, prevalent, and persistent gut bacteriophages, yet it remains uncultured and its lifestyle uncharacterized. For...
The prototypic crAssphage () is one of the most abundant, prevalent, and persistent gut bacteriophages, yet it remains uncultured and its lifestyle uncharacterized. For the last decade, crAssphage has escaped plaque-dependent culturing efforts, leading us to investigate alternative lifestyles that might explain its widespread success. Through genomic analyses and culturing, we find that crAssphage uses a phage-plasmid lifestyle to persist extrachromosomally. Plasmid-related genes are more highly expressed than those implicated in phage maintenance. Leveraging this finding, we use a plaque-free culturing approach to measure crAssphage replication in culture with and , revealing a broad host range. We demonstrate that crAssphage persists with its hosts in culture without causing major cell lysis events or integrating into host chromosomes. The ability to switch between phage and plasmid lifestyles within a wide range of hosts contributes to the prolific nature of crAssphage in the human gut microbiome.
PubMed: 38562748
DOI: 10.1101/2024.03.20.585998 -
Pharmaceutics Aug 2023The pharmacokinetic variability of nifedipine widely observed in the clinic cannot be fully explained by pharmacogenomics. As a new factor affecting drug metabolism, how...
The pharmacokinetic variability of nifedipine widely observed in the clinic cannot be fully explained by pharmacogenomics. As a new factor affecting drug metabolism, how the gut microbiota affects the pharmacokinetics of nifedipine needs to be explored. Spontaneously hypertensive rats (SHRs) have been commonly used in hypertension-related research and served as the experimental groups; Wistar rats were used as control groups. In this study, the bioavailability of nifedipine decreased by 18.62% ( < 0.05) in the SHRs compared with the Wistar rats. Changes in microbiota were associated with the difference in pharmacokinetics. The relative abundance of was negatively correlated with AUC ( = -0.881, = 0.004) and ( = -0.714, = 0.047). Analysis of serum bile acid (BA) profiles indicated that glycoursodeoxycholic acid (GUDCA) and glycochenodeoxycholic acid (GCDCA) were significantly increased in the SHRs. Compared with the Wistar rats, the expressions of CYP3A1 and PXR were upregulated and the enzyme activity of CYP3A1 increased in the SHRs. Spearman's rank correlation revealed that was negatively correlated with GUDCA ( = -0.7126, = 0.0264) and GCDCA ( = -0.6878, = 0.0339). Moreover, GUDCA was negatively correlated with ( = -0.556, = 0.025). In primary rat hepatocytes, GUDCA could induce the expressions of PXR target genes and . Furthermore, antibiotic treatments in SHRs verified the impact of microbiota on the pharmacokinetics of nifedipine. Generally, gut microbiota affects the pharmacokinetics of nifedipine through microbial biotransformation or by regulating the enzyme activity of CYP3A1.
PubMed: 37631299
DOI: 10.3390/pharmaceutics15082085 -
Foods (Basel, Switzerland) Jul 2023Amaranth has been recognized as a nutraceutical food because it contains high-quality proteins due to its adequate amino acid composition that covers the recommended...
Amaranth has been recognized as a nutraceutical food because it contains high-quality proteins due to its adequate amino acid composition that covers the recommended requirements for children and adults. Since pre-Hispanic times, amaranth has been consumed as popped grain; the popping process improves its nutritive quality and improves its digestibility. Popped amaranth consumption has been associated with the recovery of malnourished children. However, there is no information on the impact that popped amaranth consumption has on gut microbiota composition. A non-randomized pilot trial was conducted to evaluate the changes in composition, structure, and function of the gut microbiota of stunted children who received four grams of popped amaranth daily for three months. Stool and serum were collected at the beginning and at the end of the trial. Short-chain fatty acids (SCFA) were quantified, and gut bacterial composition was analyzed by gene sequencing. Biometry and hematology results showed that children had no pathology other than low height-for-age. A decrease in the relative abundance of , , and bacteria related to inflammation and colitis, and an increase in the relative abundance of and bacteria associated with health and longevity, was observed. The results demonstrate that popped amaranth is a nutritious food that helps to combat childhood malnutrition through gut microbiota modulation.
PubMed: 37509852
DOI: 10.3390/foods12142760