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Environment International Apr 2024Environmental toxicants (ETs) are associated with adverse health outcomes. Here we hypothesized that exposures to ETs are linked with obesity and insulin resistance...
Environmental toxicants (ETs) are associated with adverse health outcomes. Here we hypothesized that exposures to ETs are linked with obesity and insulin resistance partly through a dysbiotic gut microbiota and changes in the serum levels of secondary bile acids (BAs). Serum BAs, per- and polyfluoroalkyl substances (PFAS) and additional twenty-seven ETs were measured by mass spectrometry in 264 Danes (121 men and 143 women, aged 56.6 ± 7.3 years, BMI 29.7 ± 6.0 kg/m) using a combination of targeted and suspect screening approaches. Bacterial species were identified based on whole-genome shotgun sequencing (WGS) of DNA extracted from stool samples. Personalized genome-scale metabolic models (GEMs) of gut microbial communities were developed to elucidate regulation of BA pathways. Subsequently, we compared findings from the human study with metabolic implications of exposure to perfluorooctanoic acid (PFOA) in PPARα-humanized mice. Serum levels of twelve ETs were associated with obesity and insulin resistance. High chemical exposure was associated with increased abundance of several bacterial species (spp.) of genus (Anaerotruncus, Alistipes, Bacteroides, Bifidobacterium, Clostridium, Dorea, Eubacterium, Escherichia, Prevotella, Ruminococcus, Roseburia, Subdoligranulum, and Veillonella), particularly in men. Conversely, females in the higher exposure group, showed a decrease abundance of Prevotella copri. High concentrations of ETs were correlated with increased levels of secondary BAs including lithocholic acid (LCA), and decreased levels of ursodeoxycholic acid (UDCA). In silico causal inference analyses suggested that microbiome-derived secondary BAs may act as mediators between ETs and obesity or insulin resistance. Furthermore, these findings were substantiated by the outcome of the murine exposure study. Our combined epidemiological and mechanistic studies suggest that multiple ETs may play a role in the etiology of obesity and insulin resistance. These effects may arise from disruptions in the microbial biosynthesis of secondary BAs.
Topics: Gastrointestinal Microbiome; Humans; Insulin Resistance; Obesity; Middle Aged; Female; Male; Dysbiosis; Environmental Pollutants; Animals; Environmental Exposure; Mice; Bile Acids and Salts; Aged
PubMed: 38522229
DOI: 10.1016/j.envint.2024.108569 -
Biomedicines Nov 2022Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of...
OBJECTIVE
Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of COVID-19-related treatments and antibiotics on gut dysbiosis has not been clarified.
DESIGN
The prospective cohort study included hospitalized COVID-19 patients (April-December 2020). The gut microbiome composition was analysed by 16S sequencing. The gut diversity and changes in opportunistic bacteria (OBs) or symbionts were analysed according to clinical parameters, laboratory markers of disease progression, type of non-antibiotic COVID-19 treatments (NACT) and type, WHO AWaRe group, and duration of antibiotic therapy (AT).
RESULTS
A total of 82 patients (mean age 66 ± 13 years, 70% males) were enrolled. The relative abundance of was significantly correlated with duration of hospitalization, intensive care unit stay, O needs, and D-dimer, ferritin, and IL-6 blood levels. The presence of showed the highest number of correlations with NACT, AT, and AT + NACT (e.g., hydroxychloroquine ± lopinavir/ritonavir) and increased relative abundance with AWaRe Watch/Reserve antibiotics, AT duration, and combinations. Abundance of , , , and was negatively correlated with AT and corticosteroids use. Patients with increased IL-6, D-dimer, and ferritin levels receiving AT were more likely to show dysbiosis with increased abundance of and bacteria and decreased abundance of compared with those not receiving AT.
CONCLUSION
Microbiome diversity is affected by COVID-19 severity. In this context, antibiotic treatment may shift the gut microbiome composition towards OBs, particularly . The impact of treatment-driven dysbiosis on OBs infections and long-term consequences needs further study to define the role of gut homeostasis in COVID-19 recovery and inform targeted interventions.
PubMed: 36359311
DOI: 10.3390/biomedicines10112786 -
Pediatric Research Dec 2022Respiratory tract microbial dysbiosis can exacerbate inflammation and conversely inflammation may cause dysbiosis. Dysbiotic microbiome metabolites may lead to...
BACKGROUND
Respiratory tract microbial dysbiosis can exacerbate inflammation and conversely inflammation may cause dysbiosis. Dysbiotic microbiome metabolites may lead to bronchopulmonary dysplasia (BPD). Hyperoxia and lipopolysaccharide (LPS) interaction alters lung microbiome and metabolome, mediating BPD lung injury sequence.
METHODS
C57BL6/J mice were exposed to 21% (normoxia) or 70% (hyperoxia) oxygen during postnatal days (PND) 1-14. Pups were injected with LPS (6 mg/kg) or equal PBS volume, intraperitoneally on PND 3, 5, and 7. At PND14, the lungs were collected for microbiome and metabolomic analyses (n = 5/group).
RESULTS
Microbiome alpha and beta diversity were similar between groups. Metabolic changes included hyperoxia 31 up/18 down, LPS 7 up/4 down, exposure interaction 8. Hyperoxia increased Intestinimonas abundance, whereas LPS decreased Clostridiales, Dorea, and Intestinimonas; exposure interaction affected Blautia. Differential co-expression analysis on multi-omics data identified exposure-altered modules. Hyperoxia metabolomics response was integrated with a published matching transcriptome, identifying four induced genes (ALDOA, GAA, NEU1, RENBP), which positively correlated with BPD severity in a published human newborn cohort.
CONCLUSIONS
We report hyperoxia and LPS lung microbiome and metabolome signatures in a clinically relevant BPD model. We identified four genes correlating with BPD status in preterm infants that are promising targets for therapy and prevention.
IMPACT
Using multi-omics, we identified and correlated key biomarkers of hyperoxia and LPS on murine lung micro-landscape and examined their potential clinical implication, which shows strong clinical relevance for future research. Using a double-hit model of clinical relevance to bronchopulmonary dysplasia, we are the first to report integrated metabolomic/microbiome landscape changes and identify novel disease biomarker candidates.
Topics: Animals; Infant, Newborn; Humans; Mice; Bronchopulmonary Dysplasia; Hyperoxia; Animals, Newborn; Dysbiosis; Lipopolysaccharides; Multiomics; Infant, Premature; Lung; Pneumonia; Microbiota; Inflammation; Metabolome; Disease Models, Animal
PubMed: 35338351
DOI: 10.1038/s41390-022-02002-1 -
Frontiers in Immunology 2022Inflammatory bowel disease (IBD) is characterized by a disturbed gut microbiota composition. Patients with IBD have both elevated mucosal and serum levels of...
INTRODUCTION
Inflammatory bowel disease (IBD) is characterized by a disturbed gut microbiota composition. Patients with IBD have both elevated mucosal and serum levels of IgG-antibodies directed against bacterial antigens, including flagellins. In this study, we aimed to determine to which intestinal bacteria the humoral immune response is directed to in patients with IBD.
METHODS
Fecal and serum samples were collected from patients with IBD (=55) and age- and sex-matched healthy controls (=55). Fecal samples were incubated with autologous serum and IgG-coated fractions were isolated by magnetic-activated cell sorting (MACS) and its efficiency was assessed by flow cytometry. The bacterial composition of both untreated and IgG-coated fecal samples was determined by 16S rRNA-gene Illumina sequencing.
RESULTS
IgG-coated fecal samples were characterized by significantly lower microbial diversity compared to the fecal microbiome. Both in patients with IBD and controls, serum IgG responses were primarily directed to , , , , and , as well as against specific bacteria, including and (all <0.001), and to -like bacteria (<0.05). In contrast, serological IgG responses against typical commensal, anaerobic and colonic microbial species were rather low, e.g. to the members and , to , as well as to . Patients with IBD showed more IgG-coating of , , and bacteria compared to healthy controls (all <0.05). No differences in IgG-coated bacterial fractions were observed between Crohn's disease and ulcerative colitis, between active or non-active disease, nor between different disease locations.
CONCLUSION
The IgG immune response is specifically targeted at distinct intestinal bacterial genera that are typically associated with the small intestinal microbiota, whereas responses against more colonic-type commensals are lower, which was particularly the case for patients with IBD. These findings may be indicative of a strong immunological exposure to potentially pathogenic intestinal bacteria in concordance with relative immune tolerance against commensal bacteria.
Topics: Bacteria; Crohn Disease; Humans; Immunity; Immunoglobulin G; Inflammatory Bowel Diseases; RNA, Ribosomal, 16S
PubMed: 35693832
DOI: 10.3389/fimmu.2022.842911 -
Bioscience Reports Sep 2023Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron...
Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron stores, either by oral or intravenous (IV) supplementation. There is a complex bidirectional interplay between the gut microbiota, the host's iron status, and dietary iron availability. Dietary iron deficiency and supplementation can influence the gut microbiome; however, the effect of IV iron on the gut microbiome is unknown. We studied how commonly used IV iron preparations, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), affected the gut microbiome in female iron-deficient anemic mice. At the phylum level, vehicle-treated mice showed an expansion in Verrucomicrobia, mostly because of the increased abundance of Akkermansia muciniphila, along with contraction in Firmicutes, resulting in a lower Firmicutes/Bacteroidetes ratio (indicator of dysbiosis). Treatment with either FCM or FDI restored the microbiome such that Firmicutes and Bacteroidetes were the dominant phyla. Interestingly, the phyla Proteobacteria and several members of Bacteroidetes (e.g., Alistipes) were expanded in mice treated with FCM compared with those treated with FDI. In contrast, several Clostridia class members were expanded in mice treated with FDI compared with FCM (e.g., Dorea spp., Eubacterium). Our data demonstrate that IV iron increases gut microbiome diversity independently of the iron preparation used; however, differences exist between FCM and FDI treatments. In conclusion, replenishing iron stores with IV iron preparations in clinical conditions, such as inflammatory bowel disease or chronic kidney disease, could affect gut microbiome composition and consequently contribute to an altered disease outcome.
Topics: Female; Animals; Mice; Iron; Gastrointestinal Microbiome; Disaccharides; Iron, Dietary; Bacteroidetes; Firmicutes
PubMed: 37671923
DOI: 10.1042/BSR20231217 -
Diagnostic Microbiology and Infectious... Jul 2024Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies... (Review)
Review
Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies between different studies. This systematic review was conducted to investigate the characteristics of the gut microbiota in PTB patients. The MBASE, MEDLINE, Web of Science, and Cochrane Library electronic databases were systematically searched, and the quality of the retrieved studies was evaluated using the Newcastle-Ottawa scale. A total of 12 studies were finally included in the systematic review. Compared with healthy controls, the index reflecting α-diversity including the richness and/or diversity index decreased in 6 studies, while β-diversity presented significant differences in PTB patients in 10 studies. Although the specific gut microbiota alterations were inconsistent, short-chain fatty acid-producing bacteria (including Lachnospiraceae, Ruminococcus, Blautia, Dorea, and Faecalibacterium), bacteria associated with an inflammatory state (e.g., Prevotellaceae and Prevotella), and beneficial bacteria (e.g., Bifidobacteriaceae and Bifidobacterium) were commonly noted. Our systematic review identifies key evidence for gut microbiota alterations in PTB patients, in comparison with healthy controls; however, no consistent conclusion could be drawn, due to the inconsistent results and heterogeneous methodologies of the enrolled studies. Therefore, more well-designed research with standard methodologies and large sample sizes is required.
Topics: Humans; Gastrointestinal Microbiome; Tuberculosis, Pulmonary; Dysbiosis; Bacteria
PubMed: 38581928
DOI: 10.1016/j.diagmicrobio.2024.116291 -
Genes Dec 2022It is well accepted that the gut microbiota of breast-fed (BF) and formula-fed (FF) infants are significantly different. However, there is still a limited number of...
It is well accepted that the gut microbiota of breast-fed (BF) and formula-fed (FF) infants are significantly different. However, there is still a limited number of studies comparing the gut microbiota of BF and FF piglets, despite increasing numbers of FF piglets in the modern pig industry. The present study identified the differences in gut microbiota composition between BF- and FF-weaned Rongchang piglets at 30 days old, using pair-end sequencing on the Illumina HiSeq 2500 platform. The BF piglets had lower microbiota diversities than FF piglets (p < 0.05), and the community structures were well clustered as a result of each feeding pattern. Firmicutes and Bacteroidetes represented the most dominant phyla, and Ruminococcus, Prevotella, and Gemmiger were prominent genera in all piglets. Ruminococcus, Prevotella, Oscillospira, Eubacterium, Gemmiger, Dorea, and Lactobacillus populations were significantly higher, while Treponema and Coprococcus were significantly lower in BF piglets compared to FF piglets (p < 0.05). The metabolism pathways in the BF piglets were significantly different from FF piglets, which included carbohydrate and amino acid metabolism (p < 0.05). In addition, the top 10 abundance of microbiota were more or less significantly associated with the two phenotypes (p < 0.05). Collectively, these findings provide probable explanations for the importance of BF in neonates and support a theoretical basis for feeding regimes in indigenous Chinese piglets.
Topics: Animals; Swine; Gastrointestinal Microbiome; Microbiota; Weaning; Firmicutes; Bacteroidetes
PubMed: 36672790
DOI: 10.3390/genes14010049 -
MSphere Jan 2020Prebiotic oligosaccharides, such as fructooligosaccharides, are increasingly being used to modulate the composition and activity of the gut microbiota. However,...
Prebiotic oligosaccharides, such as fructooligosaccharides, are increasingly being used to modulate the composition and activity of the gut microbiota. However, carbohydrate utilization analyses and metagenomic studies recently revealed the ability of deleterious and uncultured human gut bacterial species to metabolize these functional foods. Moreover, because of the difficulties of functionally profiling transmembrane proteins, only a few prebiotic transporters have been biochemically characterized to date, while carbohydrate binding and transport are the first and thus crucial steps in their metabolization. Here, we describe the molecular mechanism of a phosphotransferase system, highlighted as a dietary and pathology biomarker in the human gut microbiome. This transporter is encoded by a metagenomic locus that is highly conserved in several human gut , including species. We developed a generic strategy to deeply analyze, and , the specificity and functionality of recombinant transporters in , combining carbohydrate utilization locus and host genome engineering and quantification of the binding, transport, and growth rates with analysis of phosphorylated carbohydrates by mass spectrometry. We demonstrated that the fructooligosaccharide transporter is specific for kestose, whether for binding, transport, or phosphorylation. This constitutes the biochemical proof of effective phosphorylation of glycosides with a degree of polymerization of more than 2, extending the known functional diversity of phosphotransferase systems. Based on these new findings, we revisited the classification of these carbohydrate transporters. Prebiotics are increasingly used as food supplements, especially in infant formulas, to modify the functioning and composition of the microbiota. However, little is currently known about the mechanisms of prebiotic recognition and transport by gut bacteria, while these steps are crucial in their metabolism. In this study, we established a new strategy to profile the specificity of oligosaccharide transporters, combining microbiomics, genetic locus and strain engineering, and state-of-the art metabolomics. We revisited the transporter classification database and proposed a new way to classify these membrane proteins based on their structural and mechanistic similarities. Based on these developments, we identified and characterized, at the molecular level, a fructooligosaccharide transporting phosphotransferase system, which constitutes a biomarker of diet and gut pathology. The deciphering of this prebiotic metabolization mechanism by a nonbeneficial bacterium highlights the controversial use of prebiotics, especially in the context of chronic gut diseases.
Topics: Bacteria; Carbohydrate Metabolism; Escherichia coli; Fermentation; Gastrointestinal Microbiome; Humans; Metabolomics; Oligosaccharides; Phosphotransferases; Prebiotics
PubMed: 31915220
DOI: 10.1128/mSphere.00771-19 -
BioMed Research International 2022Weaning is one of the most stressful periods in yak growth. However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not...
Weaning is one of the most stressful periods in yak growth. However, the impact of weaning on microbial diversity, structure, and potential function of yak feces is not clear. In this study, 12 Xinjiang yaks aged 3, 4, 5, and 6 months old were selected to collect fresh feces before and after weaning. Through 16S rRNA and ITS high-throughput sequencing, the dynamic distribution and potential function of yak fecal, bacterial, and fungal communities in each month were revealed. The study found that the richness of fungi had a significant impact on weaning. At the phylum level, , , , and , and at the genus level, , , , , , , , and were enriched in yak feces of different months old. The abundance and proportion of bacteria , , , and fungi changed significantly before and after weaning. With the increase of months, and have shown a downward trend. Through the prediction and analysis of fecal microbial function, it was found that at the level of primary pathways, weaning has a significant impact on cellular processes, environmental information processing, genetic information processing, metabolism, and organismal systems. At the level of secondary metabolic pathways, weaning has a significant impact on cell motility, signal transduction, folding, sorting and degradation, translation, amino acid metabolism, glycan biosynthesis and metabolism, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism. In addition, by analyzing the differences in functional pathways and microbial composition between sample groups of different months, it was found that the differences in functional pathways were related to the abundance differences of some microorganisms. In general, the changes in the composition and structure of yak fecal microflora may reflect the adaptability of the intestinal microbiota.
Topics: Animals; Bacteria; Bacteroidetes; Cattle; Feces; Firmicutes; Fungi; Mycobiome; RNA, Ribosomal, 16S; Weaning
PubMed: 36082156
DOI: 10.1155/2022/6297231 -
The Journal of Medical Investigation :... 2023Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut?liver axis has been recognized in...
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut?liver axis has been recognized in NASH-associated HCC. We investigated the effect of TU-100 on the intestinal microbiome and hepatocarcinogenesis in a NASH model.
METHODS
Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of NASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance.
RESULTS
At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P?0.05). At 48 weeks, the TU-100 group showed significantly lower levels of serum alanine aminotransferase. The TU-100 group also showed a lower rate of NASH than the control group (28% vs 72%?;?P?=?0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P?0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P?0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P?0.05).
CONCLUSIONS
TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model. J. Med. Invest. 70 : 66-73, February, 2023.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Carcinoma, Hepatocellular; Liver Neoplasms; Liver; Carcinogenesis
PubMed: 37164745
DOI: 10.2152/jmi.70.66