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Journal of Microbiology and... Dec 2023This study aimed to evaluate the effects of and isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db...
This study aimed to evaluate the effects of and isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of and , which were significantly increased in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the _NK4A136_group, , , , and . Untargeted metabolomics analysis showed that lotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that and _group were negatively correlated with 5-hydroxyindoleacetic acid and 13(S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of and to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.
Topics: Humans; Animals; Mice; Lactobacillaceae; Gastrointestinal Microbiome; Inulin; Tryptophan; Diabetes Mellitus, Type 2; Hydroxyindoleacetic Acid; RNA, Ribosomal, 16S; Metabolome; Linoleic Acids
PubMed: 37734909
DOI: 10.4014/jmb.2304.04039 -
BioRxiv : the Preprint Server For... Jul 2023Chronic intestinal inflammation is a poorly understood manifestation of Cystic Fibrosis (CF), which may be refractory to ion channel CFTR modulator therapy. People with...
UNLABELLED
Chronic intestinal inflammation is a poorly understood manifestation of Cystic Fibrosis (CF), which may be refractory to ion channel CFTR modulator therapy. People with CF exhibit intestinal dysbiosis which has potential for stimulating intestinal and systemic inflammation. CFTR is expressed in organ epithelia and in the leukocyte population. Here, we investigate the contribution of intestinal epithelial-specific loss of Cftr (iCftr KO) to dysbiosis and inflammation in mice treated with either of two anti-obstructive dietary regimens necessary to maintain CF mouse models (PEG laxative or a liquid diet, LiqD). Feces collected from iCftr KO mice and their wildtype (WT) sex-matched littermates were used to measure fecal calprotectin and to perform 16S rRNA sequencing to characterize the gut microbiome. Fecal calprotectin was elevated in iCftr KO relative to WT samples of mice consuming either PEG or LiqD. PEG iCftr KO mice did not show a change in α-diversity versus WT but demonstrated a significant difference in microbial composition (β-diversity) with increases in phylum , family , four genera of including , and mucolytic genus . Fecal microbiome analysis of LiqD iCftr KO mice showed both decreased α-diversity and differences in microbial composition with increases in family , families and , and enrichment of , , , mucolytic , and reduction of . It was concluded that epithelial-specific loss of Cftr is a major driver of CF intestinal dysbiosis and inflammation with significant similarities to previous studies of global Cftr KO mice.
NEW AND NOTEWORTHY
Chronic intestinal inflammation is a manifestation of cystic fibrosis (CF), a disease caused by loss of the anion channel CFTR that is expressed in many tissues. This study shows that intestinal epithelial cell-specific loss of CFTR (iCftr KO) in mice is sufficient to induce intestinal dysbiosis and inflammation. Studies were performed on mice consuming either dietary regimen (PEG laxative or liquid diet) routinely used to prevent obstruction in CF mice.
PubMed: 37546931
DOI: 10.1101/2023.07.24.550378 -
Frontiers in Nutrition 2023Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects...
Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects of kale on the intestinal environment have not yet been evaluated. This study determined how the intestinal environment, including the intestinal microbiota and its metabolome, and stool frequency are affected by the consumption of kale, in humans. A randomized controlled crossover trial, with a 4-week consumption of kale or control food, was conducted. An integrated analysis of the intestinal microbiota and metabolome was performed, and their relationship with improvements in stool frequency was analyzed. Kale intake for 4 weeks significantly increased stool frequency and altered some intestinal microbes, such as an increase in the [] group and a decrease in the [] group. Analysis of subjects with increased stool frequency revealed that this group had smaller amounts of stool before kale intake. Our findings indicate that kale modifies certain gut microbes, such as [] and [] , and improves bowel movements, particularly in those with smaller stool amounts.
PubMed: 38094924
DOI: 10.3389/fnut.2023.1247683 -
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 -
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 -
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 -
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 -
BioRxiv : the Preprint Server For... Jan 2024Tryptophan modulates disease activity and the composition of microbiota in the B6. (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut...
Tryptophan modulates disease activity and the composition of microbiota in the B6. (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intestinal inflammation. A bloom of a bacterium associated with disease flares in lupus patients, only emerged in the recipients of TC microbiota fed with high tryptophan. depletion in TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, TC mice colonized with showed higher autoimmune activation. Overall, these results suggest that the interplay of genetic and tryptophan can influence the pathogenesis of lupus through the gut microbiota.
PubMed: 38293097
DOI: 10.1101/2024.01.16.575942