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BMC Microbiology Mar 2024Extrauterine growth restriction (EUGR) represents a prevalent condition observed in preterm neonates, which poses potential adverse implications for both neonatal...
BACKGROUND
Extrauterine growth restriction (EUGR) represents a prevalent condition observed in preterm neonates, which poses potential adverse implications for both neonatal development and long-term health outcomes. The manifestation of EUGR has been intricately associated with perturbations in microbial and metabolic profiles. This study aimed to investigate the characteristics of the gut microbial network in early colonizers among preterm neonates with EUGR.
METHODS
Twenty-nine preterm infants participated in this study, comprising 14 subjects in the EUGR group and 15 in the normal growth (AGA) group. Meconium (D1) and fecal samples were collected at postnatal day 28 (D28) and 1 month after discharge (M1). Subsequently, total bacterial DNA was extracted and sequenced using the Illumina MiSeq system, targeting the V3-V4 hyper-variable regions of the 16S rRNA gene.
RESULTS
The outcomes of principal coordinates analysis (PCoA) and examination of the microbial network structure revealed distinctive developmental trajectories in the gut microbiome during the initial three months of life among preterm neonates with and without EUGR. Significant differences in microbial community were observed at the D1 (P = 0.039) and M1 phases (P = 0.036) between the EUGR and AGA groups, while a comparable microbial community was noted at the D28 phase (P = 0.414). Moreover, relative to the AGA group, the EUGR group exhibited significantly lower relative abundances of bacteria associated with secretion of short-chain fatty acids, including Lactobacillus (P = 0.041) and Parabacteroides (P = 0.033) at the D1 phase, Bifidobacterium at the D28 phase, and genera Dysgonomonas (P = 0.042), Dialister (P = 0.02), Dorea (P = 0.042), and Fusobacterium (P = 0.017) at the M1 phase.
CONCLUSION
Overall, the present findings offer crucial important insights into the distinctive gut microbial signatures exhibited by earlier colonizers in preterm neonates with EUGR. Further mechanistic studies are needed to establish whether these differences are the cause or a consequence of EUGR.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Gestational Age; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Birth Weight
PubMed: 38461289
DOI: 10.1186/s12866-024-03234-3 -
Digestive Diseases and Sciences Apr 2024Previous studies showed that patients with Severe IBS respond better to fecal microbiota transplantation (FMT) than do those with Moderate IBS. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies showed that patients with Severe IBS respond better to fecal microbiota transplantation (FMT) than do those with Moderate IBS.
AIMS
The present study aimed to determine the effects of the transplant dose, route of administering it and repeating FMT on this difference.
METHODS
This study included 186 patients with IBS randomized 1:1:1 into groups with a 90-g transplant administered once to the colon (LI), once to the duodenum (SI), or twice to the distal duodenum twice (repeated SI). The patients provided a fecal sample and were asked to complete three questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and Dysbiosis index were analyzed using 16 S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9.
RESULTS
There was no difference in the response rates between severe IBS and moderate IBS for SI and repeated SI at all observation intervals after FMT. In the LI group, the response rate at 3 months after FMT was higher for moderate IBS than for severe IBS. The levels of Dorea spp. were higher and those of Streptococcus salivarius subsp. Thermophilus, Alistipes spp., Bacteroides and Prevotella spp., Parabacteroides johnsoni and Parabacteroides spp. were lower in moderate IBS than in severe IBS.
CONCLUSIONS
There was no difference in the response to FMT between severe and moderate IBS when a 90-g transplant was administered to the small intestine. The difference in the bacterial profile between severe and moderate IBS may explain the difference in symptoms between these patients. ( www.
CLINICALTRIALS
gov : NCT04236843).
Topics: Humans; Duodenum; Fecal Microbiota Transplantation; Feces; Gastrointestinal Microbiome; Irritable Bowel Syndrome; Treatment Outcome
PubMed: 38446309
DOI: 10.1007/s10620-024-08369-x -
Frontiers in Microbiology 2024Diarrheal acquired immune deficiency syndrome (AIDS) seriously affects the quality of life of patients. In this study, we analyzed the differences in the intestinal...
Diarrheal acquired immune deficiency syndrome (AIDS) seriously affects the quality of life of patients. In this study, we analyzed the differences in the intestinal microbiota among healthy individuals, AIDS patients without diarrhea and AIDS patients with diarrhea through high-throughput sequencing. The microbial diversity in the intestines of patients in the AIDS diarrhea group was significantly increased, and after treatment with Xielikang, the intestinal microbial diversity returned to the baseline level. At the phylum level, compared those in to the healthy (ZC) and AIDS non diarrhea (FN) groups, the relative abundances of Bacteroidetes and Verrucomirobia in the AIDS diarrhea (FA) group before treatment were significantly increased, while the relative abundance of Firmicutes was significantly decreased. Similarly, compared with those in the FA group, the relative abundances of Bacteroidea and Firmicutes in the AIDS diarrhea (FB) group after treatment were significantly increased, while the relative abundance of Firmicutes was significantly decreased after treatment. Additionally, there was no significant difference between the ZC and FN groups. At the genus level, compared with those in the ZC group, the relative abundance of and in the FA group was significantly increased, while the relative abundances of and was significantly decreased compared to that in the ZC group. After treatment with Xielikang, the relative abundance of and in the FB group were significantly decreased, while the relative abundances of and were significantly increased than those in the FA group; moreover, there was no significant difference between the ZC and FN groups. The functional prediction results showed that the ketodeoxyoctonate (Kdo) transfer to lipid IVA III and the superpathway of N-acetylglucosamine pathways in the AIDS diarrhea group were significantly altered. The correlation analysis results showed that was positively correlated with inflammatory factors, while and were negatively correlated with inflammatory factors. The composition and function of the intestinal microbiota changed significantly in AIDS diarrhea patients, which affected the immune function of the host. The Xielikang capsule modulated the composition of the intestinal microbiota in AIDS diarrhea patients and thus improved immune function and reduced diarrheal symptoms.
PubMed: 38435694
DOI: 10.3389/fmicb.2024.1346955 -
BMC Cardiovascular Disorders Mar 2024Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to...
AIMS
Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to investigate the potentially causal relationships between the intestinal flora and blood lipids.
METHODS
We performed a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between intestinal flora and blood lipids. Summary statistics of genome-wide association studies (GWASs) for the 211 intestinal flora and blood lipid traits (n = 5) were obtained from public datasets. Five recognized MR methods were applied to assess the causal relationship with lipids, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates.
RESULTS
The results indicated a potential causal association between 19 intestinal flora and dyslipidemia in humans. Genus Ruminococcaceae, Christensenellaceae, Parasutterella, Terrisporobacter, Parabacteroides, Class Erysipelotrichia, Family Erysipelotrichaceae, and order Erysipelotrichales were associated with higher dyslipidemia, whereas genus Oscillospira, Peptococcus, Ruminococcaceae UCG010, Ruminococcaceae UCG011, Dorea, and Family Desulfovibrionaceae were associated with lower dyslipidemia. After using the Bonferroni method for multiple testing correction, Only Desulfovibrionaceae [Estimate = -0.0418, 95% confidence interval [CI]: 0.9362-0.9826, P = 0.0007] exhibited stable and significant negative associations with ApoB levels. The inverse MR analysis did not find a significant causal effect of lipids on the intestinal flora. Additionally, no significant heterogeneity or horizontal pleiotropy for IVs was observed in the analysis.
CONCLUSION
The study suggested a causal relationship between intestinal flora and dyslipidemia. These findings will provide a meaningful reference to discover dyslipidemia for intervention to address the problems in the clinic.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Atherosclerosis; Dyslipidemias
PubMed: 38431594
DOI: 10.1186/s12872-024-03804-3 -
The American Journal of Clinical... May 2024The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.
BACKGROUND
The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood.
OBJECTIVES
Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors.
METHODS
A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota.
RESULTS
Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors.
CONCLUSIONS
An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).
Topics: Humans; Diet, Mediterranean; Gastrointestinal Microbiome; Middle Aged; Male; Female; Aged; Exercise; Metabolome; Feces; Life Style; Cardiovascular Diseases
PubMed: 38428742
DOI: 10.1016/j.ajcnut.2024.02.021 -
MedRxiv : the Preprint Server For... Feb 2024Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features...
OBJECTIVE
Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes.
DESIGN
We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM).
RESULTS
Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM.
CONCLUSION
Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers.
KEY MESSAGES
The intestinal microbiota and its metabolites (e.g., short chain fatty acids [SCFA]) modulate irritable bowel syndrome (IBS) pathophysiology. We studied microbe-SCFA associations across IBS subtypes and endophenotypes to demonstrate (1) the intestinal microbiome plays distinct roles across IBS subtypes, (2) microbial substrate preferences vary between IBS subtypes and influences stool form, and (3) microbe-SCFA patterns may reveal key taxa that underlie shared and distinct microbial mechanisms across the IBS spectrum. Findings demonstrate that structural and functional features of the intestinal microbiome may represent unbiased microbial biomarkers for clinical and mechanistic IBS subtypes. Further study of these putative microbial targets as well as their interactions with diet- and host-specific traits should be pursued to develop individualized microbiome-based approached to IBS management.
PubMed: 38352442
DOI: 10.1101/2024.01.31.24302084 -
Journal of Clinical and Translational... Feb 2024Accumulating evidence highlights the association between the gut microbiota and liver cirrhosis. However, the role of the gut microbiota in liver cirrhosis remains...
BACKGROUND AND AIMS
Accumulating evidence highlights the association between the gut microbiota and liver cirrhosis. However, the role of the gut microbiota in liver cirrhosis remains unclear.
METHODS
We first assessed the differences in the composition of the bacterial community between CCl4-induced liver cirrhosis and control mice using 16S rRNA sequencing. We then performed a two-sample Mendelian randomization (MR) analysis to reveal the underlying causal relationship between the gut microbiota and liver cirrhosis. Causal relationships were analyzed using primary inverse variance weighting (IVW) and other supplemental MR methods. Furthermore, fecal samples from liver cirrhosis patients and healthy controls were collected to validate the results of the MR analysis.
RESULTS
Analysis of 16S rRNA sequencing indicated significant differences in gut microbiota composition between the cirrhosis and control groups. IVW analyses suggested that Alphaproteobacteria, Bacillales, NB1n, Rhodospirillales, , , and were positively correlated with the risk of liver cirrhosis, whereas , , , and displayed the opposite effects. However, the weighted median and MR-PRESSO estimates further showed that only and presented stable negative associations with liver cirrhosis. No significant heterogeneity or horizontal pleiotropy was observed in the sensitivity analysis. Furthermore, the result of 16S rRNA sequencing also showed that healthy controls had a higher relative abundance of and than liver cirrhosis patients.
CONCLUSIONS
Our study provides new causal evidence for the link between gut microbiota and liver cirrhosis, which may contribute to the discovery of novel strategies to prevent liver cirrhosis.
PubMed: 38343609
DOI: 10.14218/JCTH.2023.00259 -
Translational Psychiatry Jan 2024The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal...
BACKGROUND
The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR).
METHODS
The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD's causal effects on the relative abundances of specific features of the gut microbiome.
RESULTS
In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability.
CONCLUSION
Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
Topics: Humans; Gastrointestinal Microbiome; Stress Disorders, Post-Traumatic; Genome-Wide Association Study; Reproducibility of Results; Dietary Supplements
PubMed: 38296956
DOI: 10.1038/s41398-024-02765-7 -
Frontiers in Endocrinology 2023Chronic intermittent hypoxia (CIH) is a key characteristic of obstructive sleep apnea (OSA) syndrome, a chronic respiratory disorder. The mechanisms of CIH-induced...
AIM
Chronic intermittent hypoxia (CIH) is a key characteristic of obstructive sleep apnea (OSA) syndrome, a chronic respiratory disorder. The mechanisms of CIH-induced metabolic disturbance and histopathological damage remain unclear.
METHODS
CIH-induced rats underwent daily 8-h CIH, characterized by oxygen levels decreasing from 21% to 8.5% over 4 min, remaining for 2 min, and quickly returning to 21% for 1 min. The control rats received a continuous 21% oxygen supply. The levels of hypersensitive C reactive protein (h-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and nuclear factor kappa-B (NF-κB) were measured by ELISA. Histological analysis of the soft palates was conducted using HE staining. The microbial profiling of fecal samples was carried out by Accu16STM assay. Untargeted metabolomics of serum and soft palate tissue samples were analyzed by UPLC-MS. The protein expression of cAMP-related pathways in the soft palate was determined by Western blot.
RESULTS
After 28 h of CIH induction, a significant increase in pro-inflammatory cytokines was observed in the serum, along with mucosal layer thickening and soft palate tissue hypertrophy. CIH induction altered the diversity and composition of fecal microbiota, specifically reducing beneficial bacteria while increasing harmful bacteria/opportunistic pathogens. Notably, CIH induction led to a significant enrichment of genera such as , , , , , and genera. Meanwhile, Additionally, CIH induction had a notable impact on 108 serum marker metabolites. These marker metabolites, primarily involving amino acids, organic acids, and a limited number of flavonoids or sterols, were associated with protein transport, digestion and absorption, amino acid synthesis and metabolism, as well as cancer development. Furthermore, these differential serum metabolites significantly affected 175 differential metabolites in soft palate tissue, mainly related to cancer development, signaling pathways, amino acid metabolism, nucleotide precursor or intermediate metabolism, respiratory processes, and disease. Importantly, CIH induction could significantly affect the expression of the cAMP pathway in soft palate tissue.
CONCLUSIONS
Our findings suggest that targeting differential metabolites in serum and soft palate tissue may represent a new approach to clinical intervention and treatment of OSA simulated by the CIH.
Topics: Rats; Animals; Rats, Sprague-Dawley; Gastrointestinal Microbiome; Chromatography, Liquid; Dysbiosis; Tandem Mass Spectrometry; Hypoxia; Sleep Apnea, Obstructive; Metabolome; Oxygen; Amino Acids; Neoplasms
PubMed: 38283743
DOI: 10.3389/fendo.2023.1224396 -
Frontiers in Microbiology 2023Early life determinants of the development of gut microbiome composition in infants have been widely investigated; however, if early life pollutant exposures, such as...
BACKGROUND
Early life determinants of the development of gut microbiome composition in infants have been widely investigated; however, if early life pollutant exposures, such as tobacco or mercury, have a persistent influence on the gut microbial community, its stabilization at later childhood remains largely unknown.
OBJECTIVE
In this exposome-wide study, we aimed at identifying the contribution of exposure to tobacco and mercury from the prenatal period to childhood, to individual differences in the fecal microbiome composition of 7-year-old children, considering co-exposure to a width of established lifestyle and clinical determinants.
METHODS
Gut microbiome was studied by 16S rRNA amplicon sequencing in 151 children at the genus level. Exposure to tobacco was quantified during pregnancy through questionnaire (active tobacco consumption, second-hand smoking -SHS) and biomonitoring (urinary cotinine) at 4 years (urinary cotinine, SHS) and 7 years (SHS). Exposure to mercury was quantified during pregnancy (cord blood) and at 4 years (hair). Forty nine other potential environmental determinants (12 at pregnancy/birth/infancy, 15 at 4 years and 22 at 7 years, such as diet, demographics, quality of living/social environment, and clinical records) were registered. We used multiple models to determine microbiome associations with pollutants including multi-determinant multivariate analysis of variance and linear correlations (wUnifrac, Bray-Curtis and Aitchison ß-diversity distances), single-pollutant permutational multivariate analysis of variance adjusting for co-variates (Aitchison), and multivariable association model with single taxa (MaAsLin2; genus). Sensitivity analysis was performed including genetic data in a subset of 107 children.
RESULTS
Active smoking in pregnancy was systematically associated with microbiome composition and ß-diversity ( 2-4%, < 0.05, Aitchison), independently of other co-determinants. However, in the adjusted single pollutant models (PERMANOVA), we did not find any significant association. An increased relative abundance of and decreased relative abundance of were associated with smoking during pregnancy ( < 0.05).
DISCUSSION
Our findings suggest a long-term sustainable effect of prenatal tobacco exposure on the children's gut microbiota. This effect was not found for mercury exposure or tobacco exposure during childhood. Assessing the role of these exposures on the children's microbiota, considering multiple environmental factors, should be further investigated.
PubMed: 38249448
DOI: 10.3389/fmicb.2023.1258988