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Frontiers in Cellular and Infection... 2024Children have regional dynamics in the gut microbiota development trajectory. Hitherto, the features and influencing factors of the gut microbiota and fecal and plasma...
INTRODUCTION
Children have regional dynamics in the gut microbiota development trajectory. Hitherto, the features and influencing factors of the gut microbiota and fecal and plasma metabolites in children from Northwest China remain unclear.
METHODS
Shotgun metagenomic sequencing and untargeted metabolomics were performed on 100 healthy volunteers aged 2-12 years.
RESULTS
Age, body mass index (BMI), regular physical exercise (RPE), and delivery mode (DM) significantly affect gut microbiota and metabolites. , , , , and predicted pathway propanoate production were significantly increased with age while , , and carbohydrate degradation were decreased. Fecal metabolome revealed that the metabolism of caffeine, amino acids, and lipid significantly increased with age while galactose metabolism decreased. Noticeably, BMI was positively associated with pathogens including , , , and amino acid metabolism but negatively associated with beneficial , , , and caffeine metabolism. RPE has increased probiotic and , acetate and lactate production, and major nutrient metabolism in gut and plasma, but decreased pathobiont , taurine degradation, and pentose phosphate pathway. Interestingly, DM affects the gut microbiota and metabolites throughout the whole childhood. , , , primary bile acid, and neomycin biosynthesis were enriched in eutocia, while anti-inflammatory , , , and pathogenic , , and amino acid metabolism were enriched in Cesarean section children.
DISCUSSION
Our results provided theoretical and data foundation for the gut microbiota and metabolites in preadolescent children's growth and development in Northwest China.
Topics: Pregnancy; Child; Humans; Female; Gastrointestinal Microbiome; Caffeine; Cesarean Section; Urban Population; Metabolome; Amino Acids
PubMed: 38585649
DOI: 10.3389/fcimb.2024.1374544 -
Food and Chemical Toxicology : An... Oct 2023Ulcerative colitis (UC) is believed to arise from an imbalance between the intestinal microbiota and mucosal immunity, leading to excessive intestinal inflammation....
Ulcerative colitis (UC) is believed to arise from an imbalance between the intestinal microbiota and mucosal immunity, leading to excessive intestinal inflammation. Modulating the gut microbial community through dietary components presents a valuable strategy in aiding the treatment of UC. In this study, esters formed by binding of well-known prebiotics, fructooligosaccharides (FOS), with short chain fatty acids (SCFAs) via both enzymatic and chemical methods were evaluated for their impact on the gut microbiota of UC patients. An in vitro human colonic fermentation model was employed to monitor changes in total carbohydrates and SCFAs production during the fermentation of these esters by microbiota from patients with active and remission UC. The results showed that pronounced abundance of [Ruminococcus]_gnavus_group, Escherichia_Shigella, Lachnoclostridium, Klebsiella and other potential pathogens were detected in the fecal samples from UC patients, with a milder condition observed during the remission phase. Significant higher levels of corresponding SCFA were observed in the groups with addition of FOS-SCFAs esters during fermentation. Butyrylated fructooligosaccharides (B-FOS) and propionylated fructooligosaccharides (P-FOS) by enzymatic synthesis successfully promoted the proliferation of Bifidobacterium and inhibited Clostridium_sensu_stricto_1 and Klebsiella. Overall, B-FOS and P-FOS exhibit promising potential for restoring intestinal homeostasis and alleviating intestinal inflammation in individuals with UC.
Topics: Humans; Colitis, Ulcerative; Prebiotics; Fermentation; Fatty Acids, Volatile; Feces; Microbiota; Inflammation
PubMed: 37652126
DOI: 10.1016/j.fct.2023.114009 -
Food & Function Feb 2024Fructooligosaccharides (FOS) and inulin are beneficial for human health. However, their benefits differ in individuals who consume prebiotics. Several factors contribute...
Fructooligosaccharides (FOS) and inulin are beneficial for human health. However, their benefits differ in individuals who consume prebiotics. Several factors contribute to this variation, including host genetics and differences in the gut microbiota. and are strong carbohydrate-utilizing bacteria in the gut, and the level of the / (Ba/Bi) ratio in the gut is closely related to the body's ability to utilize prebiotics. However, how to select the type of prebiotics more beneficial for populations with specific Ba/Bi backgrounds and the underlying regulatory mechanisms remain unclear. Here, we explored the dynamics of the gut microbiota and metabolic functions during the fermentation of FOS and inulin in two different groups: / high (H) and / low (L). This study revealed that the baseline Ba/Bi ratio had a greater impact on the gut microbiota compared to prebiotic species. Noticeable differences were observed between the two groups after prebiotic intervention, with the H group being more likely to benefit from the prebiotic intervention. Compared to the L group, the H group exhibited significantly higher microbial α-diversity; the co-abundance response group 1 (CARG1) members and involved in the synthesis of propionic and butyric acids increased significantly, the abundance of pathogenic bacteria such as decreased significantly, and the ability to degrade carbohydrates and synthesize fatty acids was greater. Regression modeling showed that the key microbiota could predict the short-chain fatty acid (SCFA) levels, with FOS associated with the ecological roles of CARG2 and CARG7 and inulin associated with CARG4, which provides the basis for the use of prebiotics in nutritional applications and the stratification of populations based on pertinent microbiota profiles to explain the incongruent health effects in human intervention studies.
Topics: Humans; Inulin; Gastrointestinal Microbiome; Feces; Oligosaccharides; Prebiotics; Bacteria; Fermentation; Bifidobacterium
PubMed: 38214586
DOI: 10.1039/d3fo04855a -
ACS Nano Jun 2024Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health...
Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F and F generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F and F mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of and and a decreased abundance of were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.
PubMed: 38935618
DOI: 10.1021/acsnano.4c06298 -
BioRxiv : the Preprint Server For... Apr 2024There is growing appreciation that commensal bacteria impact the outcome of viral infections, though the specific bacteria and their underlying mechanisms remain poorly...
There is growing appreciation that commensal bacteria impact the outcome of viral infections, though the specific bacteria and their underlying mechanisms remain poorly understood. Studying a simian-human immunodeficiency virus (SHIV)-challenged cohort of pediatric nonhuman primates, we bioinformatically associated Lactobacillus gasseri and the bacterial family Lachnospiraceae with enhanced resistance to infection. We experimentally validated these findings by demonstrating two different Lachnospiraceae isolates, Clostridium immunis and Ruminococcus gnavus, inhibited HIV replication in vitro and ex vivo. Given the link between tryptophan catabolism and HIV disease severity, we found that an isogenic mutant of C. immunis that lacks the aromatic amino acid aminotransferase (ArAT) gene, which is key to metabolizing tryptophan into 3-indolelactic acid (ILA), no longer inhibits HIV infection. Intriguingly, we confirmed that a second commensal bacterium also inhibited HIV in an ArAT-dependent manner, thus establishing the generalizability of this finding. In addition, we found that purified ILA inhibited HIV infection by agonizing the aryl hydrocarbon receptor (AhR). Given that the AhR has been implicated in the control of multiple viral infections, we demonstrated that C. immunis also inhibited human cytomegalovirus (HCMV) infection in an ArAT-dependent manner. Importantly, metagenomic analysis of individuals at-risk for HIV revealed that those who ultimately acquired HIV had a lower fecal abundance of the bacterial ArAT gene compared to individuals who did not, which indicates our findings translate to humans. Taken together, our results provide mechanistic insights into how commensal bacteria decrease susceptibility to viral infections. Moreover, we have defined a microbiota-driven antiviral pathway that offers the potential for novel therapeutic strategies targeting a broad spectrum of viral pathogens.
PubMed: 38659737
DOI: 10.1101/2024.04.21.589969 -
Antibiotics (Basel, Switzerland) Nov 2023Graft-versus-host disease (GvHD) is a severe complication after hematopoietic stem cell transplantation (HSCT). Our study focused on identifying multidrug-resistant...
High Diversity but Monodominance of Multidrug-Resistant Bacteria in Immunocompromised Pediatric Patients with Acute Lymphoblastic Leukemia Developing GVHD Are Not Associated with Changes in Gut Mycobiome.
Graft-versus-host disease (GvHD) is a severe complication after hematopoietic stem cell transplantation (HSCT). Our study focused on identifying multidrug-resistant (MDR) gut bacteria associated with GvHD-prone guts and association with gut microbiota (GM) diversity, bacteriome, and mycobiome composition in post-HSCT patients. We examined 11 pediatric patients with acute lymphoblastic leukemia (ALL), including six with GvHD, within three time points: seven days pre-HSCT, seven days post-, and 28 days post-HSCT. The gut microbiome and its resistome were investigated using metagenomic sequencing, taxonomically classified with Kraken2, and statistically evaluated for significance using appropriate tests. We observed an increase in the abundance of MDR bacteria, mainly strains carrying , , , , and genes, in GvHD patients one week post-HSCT. Conversely, non-GvHD patients had more MDR beneficial bacteria pre-HSCT, promoting immunosurveillance, with resistance genes increasing one-month post-HSCT. MDR beneficial bacteria included the anti-inflammatory , , and , while most MDR bacteria represented the dominant species of GM. Changes in the gut mycobiome were not associated with MDR bacterial monodominance or GvHD. Significant α-diversity decline (Shannon index) one week and one month post-HSCT in GvHD patients ( < 0.05) was accompanied by increased and decreased post-HSCT. Our findings suggest that MDR commensal gut bacteria may preserve diversity and enhance immunosurveillance, potentially preventing GvHD in pediatric ALL patients undergoing HSCT. This observation has therapeutic implications.
PubMed: 38136701
DOI: 10.3390/antibiotics12121667 -
PNAS Nexus Jul 2023The South Shetland Trough, Antarctica, is an underexplored region for microbiological and biotechnological exploitation. Herein, we describe the isolation and...
The South Shetland Trough, Antarctica, is an underexplored region for microbiological and biotechnological exploitation. Herein, we describe the isolation and characterization of the novel bacterium sp. nov. WUR7 from a deep-sea environment. We explored its chemical diversity via a metabologenomics approach, wherein the OSMAC strategy was strategically employed to upregulate cryptic genes for secondary metabolite production. Based on hybrid de novo whole genome sequencing and digital DNA-DNA hybridization, isolate WUR7 was identified as a novel species from the Gram-negative genus . Its genome was mined for the presence of biosynthetic gene clusters with limited results. However, extensive investigation of its metabolism uncovered an unusual tryptophan decarboxylase with high sequence homology and conserved structure of the active site as compared to ZP_02040762, a highly specific tryptophan decarboxylase from . Therefore, WUR7's metabolism was directed toward indole-based alkaloid biosynthesis by feeding it with -tryptophan. As expected, its metabolome profile changed dramatically, by triggering the extracellular accumulation of a massive array of metabolites unexpressed in the absence of tryptophan. Untargeted LC-MS/MS coupled with molecular networking, followed along with chemoinformatic dereplication, allowed for the annotation of 10 indole alkaloids, belonging to β-carboline, bisindole, and monoindole classes, alongside several unknown alkaloids. These findings guided us to the isolation of a new natural bisindole alkaloid 8,9-dihydrocoscinamide B (), as the first alkaloid from the genus , whose structure was elucidated on the basis of extensive 1D and 2D NMR and HR-ESIMS experiments. This comprehensive strategy allowed us to unlock the previously unexploited metabolome of sp. nov. WUR7.
PubMed: 37448956
DOI: 10.1093/pnasnexus/pgad221 -
Environment International Jun 2024Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect...
BACKGROUND
Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB.
OBJECTIVE
We aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB.
METHODS
A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in α-synuclein tg DLB/PD mice.
RESULTS
The DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice.
CONCLUSION
Our study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.
PubMed: 38908272
DOI: 10.1016/j.envint.2024.108806 -
Frontiers in Microbiology 2024infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut...
infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ ( = 20) and CDI- ( = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens and in CDI+ compared to CDI- samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI-, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by . This provides evidence of another possible contributor to 's resistance to antibiotics and frequent recurrence . Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI.
PubMed: 38680911
DOI: 10.3389/fmicb.2024.1398018 -
Cancers Oct 2023Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in...
Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with and were elevated in mucosa from polyp patients, while ASVs associated with , , and were relatively decreased. Only was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche.
PubMed: 37894412
DOI: 10.3390/cancers15205045