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Marine Drugs May 2024hydrolysate (PMH) has been proved to have the effect of ameliorating disorders of glucose and lipid metabolism in db/db mice, but the mechanism of its hyperglycemia...
hydrolysate (PMH) has been proved to have the effect of ameliorating disorders of glucose and lipid metabolism in db/db mice, but the mechanism of its hyperglycemia effect is still unclear. Bacterial communities in fecal samples from a normal control group, a diabetic control group, and a PMH-treated diabetes mellitus type 2 (T2DM) group were analyzed by 16S gene sequencing. Nano LC-MS/MS was used to analyze mice neuropeptides and proteomes. The 16S rDNA sequencing results showed that PMH modulated the structure and composition of the gut microbiota and improved the structure and composition of Firmicutes and Bacteroidetes at the phylum level and and at the family level. Furthermore, the expressions of functional proteins of the central nervous system, immune response-related protein, and proteins related to fatty acid oxidation in the brain disrupted by an abnormal diet were recovered by PMH. PMH regulates the brain neuropeptidome and proteome and further regulates blood glucose in diabetic mice through the gut-brain axis. PMH may be used as a prebiotic agent to attenuate T2DM, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.
Topics: Animals; Gastrointestinal Microbiome; Mice; Proteome; Diabetes Mellitus, Type 2; Brain; Diabetes Mellitus, Experimental; Male; Brain-Gut Axis; Blood Glucose; Mice, Inbred C57BL; Prebiotics; Feces
PubMed: 38921560
DOI: 10.3390/md22060249 -
Frontiers in Microbiology 2024Commensal intestinal bacteria shape our microbiome and have decisive roles in preserving host metabolic and immune homeostasis. They conspicuously impact disease...
Longitudinal microbiome investigation throughout prion disease course reveals pre- and symptomatic compositional perturbations linked to short-chain fatty acid metabolism and cognitive impairment in mice.
Commensal intestinal bacteria shape our microbiome and have decisive roles in preserving host metabolic and immune homeostasis. They conspicuously impact disease development and progression, including amyloid-beta (Aβ) and alpha (α)-synuclein pathology in neurodegenerative diseases, conveying the importance of the brain-gut-microbiome axis in such conditions. However, little is known about the longitudinal microbiome landscape and its potential clinical implications in other protein misfolding disorders, such as prion disease. We investigated the microbiome architecture throughout prion disease course in mice. Fecal specimens were assessed by 16S ribosomal RNA sequencing. We report a temporal microbiome signature in prion disease and uncovered alterations in Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, and Muribaculaceae family members in this disease. Moreover, we determined the enrichment of Bilophila, a microorganism connected to cognitive impairment, long before the clinical manifestation of disease symptoms. Based on temporal microbial abundances, several associated metabolic pathways and resulting metabolites, including short-chain fatty acids, were linked to the disease. We propose that neuroinflammatory processes relate to perturbations of the intestinal microbiome and metabolic state by an interorgan brain-gut crosstalk. Furthermore, we describe biomarkers possibly suitable for early disease diagnostics and anti-prion therapy monitoring. While our study is confined to prion disease, our discoveries might be of equivalent relevance in other proteinopathies and central nervous system pathologies.
PubMed: 38919500
DOI: 10.3389/fmicb.2024.1412765 -
Frontiers in Genetics 2024An increasing amount of evidence suggests that gastrointestinal diseases are risk factors for herpes zoster (HZ) and postherpetic neuralgia (PHN). Among them, the gut...
BACKGROUND
An increasing amount of evidence suggests that gastrointestinal diseases are risk factors for herpes zoster (HZ) and postherpetic neuralgia (PHN). Among them, the gut microbiota may play a crucial role in this process. Therefore, this study aims to explore the potential causal association between the gut microbiota and HZ and PHN.
METHODS
Bidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between HZ and PHN and the gut microbiota. Gut microbiota data were derived from the MiBioGen consortium, while HZ and PHN data were obtained from the FinnGen database. We selected single-nucleotide polymorphisms (SNPs) as instrumental variables with a threshold of < 1 × 10⁻⁵ for the association with the gut microbiota in forward MR analysis and < 5 × 10 for the association with HZ or PHN in reverse MR analysis and then removed SNPs in linkage disequilibrium ( < 0.001) within a distance of 10,000 kb for both the gut microbiota and HZ and PHN. These SNPs were utilized to assess the causal effect between exposures and outcomes using inverse-variance weighting (IVW), MR-Egger, weighted mean, and weighted median tests.
RESULTS
The class Deltaproteobacteria, order Desulfovibrionales, family Desulfovibrionaceae, and genus were found to reduce the risk of HZ, while the phylum Cyanobacteria, genus group appeared to increase it. The class Coriobacteriia, order Coriobacteriales, family Coriobacteriaceae, genus and genus were found to reduce the risk of PHN, while the genus , genus group, and genus appeared to increase it. Moreover, the onset of HZ was found to increase the level of the genus group. These findings remained robust and unaffected by heterogeneity or horizontal pleiotropy among SNPs in both forward and reverse MR analysis.
CONCLUSION
This MR study provided evidence supporting a potential causal relationship between the gut microbiota and HZ and PHN. Moreover, we found that the causal effect between the gut microbiota and HZ is bidirectional. Further studies are required to clarify the biological mechanisms linking the gut microbiota and these conditions.
PubMed: 38846958
DOI: 10.3389/fgene.2024.1366824 -
Frontiers in Cellular and Infection... 2024The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of...
BACKGROUND
The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function.
MATERIALS AND METHODS
Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV, FVC, and FEV/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results.
RESULTS
The MR results confirmed four taxa were found causally associated with the risk of IPF. (OR=0.773, 95% CI: 0.610-0.979, p=0.033), (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in , and being the most prominent beneficial microbiota, while those in , and were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV and FVC on the increased abundance of six taxa (, and ) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF.
CONCLUSION
The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.
Topics: Humans; Mendelian Randomization Analysis; Idiopathic Pulmonary Fibrosis; Gastrointestinal Microbiome; Genome-Wide Association Study; Lung; Respiratory Function Tests; Genetic Predisposition to Disease
PubMed: 38841114
DOI: 10.3389/fcimb.2024.1348685 -
PloS One 2024Opisthorchis viverrini (O. viverrini, Ov) infection and consumption of high-fat and high-fructose (HFF) diet exacerbate liver and kidney disease. Here, we investigated...
BACKGROUND
Opisthorchis viverrini (O. viverrini, Ov) infection and consumption of high-fat and high-fructose (HFF) diet exacerbate liver and kidney disease. Here, we investigated the effects of a combination of O. viverrini infection and HFF diet on kidney pathology via changes in the gut microbiome and host proteome in hamsters.
METHODOLOGY/PRINCIPAL FINDINGS
Twenty animals were divided into four groups; 1) fed a normal diet not infected with O. viverrini (normal group), 2) fed an HFF diet and not infected with O. viverrini (HFF), 3) fed a normal diet and infected with O. viverrini (Ov), and 4) fed an HFF diet and infected with O. viverrini (HFFOv). DNA was extracted from fecal samples and the V3-V4 region of the bacterial 16S rRNA gene sequenced on an Illumina MiSeq sequencing platform. In addition, LC/MS-MS analysis was done. Histopathological studies and biochemical assays were also conducted. The results indicated that the HFFOv group exhibited the most severe kidney injury, manifested as elevated KIM-1 expression and accumulation of fibrosis in kidney tissue. The microbiome of the HFFOv group was more diverse than in the HFF group: there were increased numbers of Ruminococcaceae, Lachnospiraceae, Desulfovibrionaceae and Akkermansiaceae, but fewer Eggerthellaceae. In total, 243 host proteins were identified across all groups. Analysis using STITCH predicted that host proteome changes may lead to leaking of the gut, allowing molecules such as soluble CD14 and p-cresol to pass through to promote kidney disease. In addition, differential expression of TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Tab2, involving renal inflammation and injury) are predicted to be associated with kidney disease.
CONCLUSIONS/SIGNIFICANCE
The combination of HFF diet and O. viverrini infection may promote kidney injury through alterations in the gut microbiome and host proteome. This knowledge may suggest an effective strategy to prevent kidney disease beyond the early stages.
Topics: Animals; Fructose; Opisthorchiasis; Diet, High-Fat; Metagenomics; Cricetinae; Proteomics; Gastrointestinal Microbiome; Kidney Diseases; Opisthorchis; Male; Proteome; Kidney; Mesocricetus; RNA, Ribosomal, 16S
PubMed: 38814931
DOI: 10.1371/journal.pone.0301907 -
FEMS Microbiology Ecology Jun 2024Mucin is a glycoprotein secreted throughout the mammalian gastrointestinal tract that can support endogenous microorganisms in the absence of complex polysaccharides....
Mucin is a glycoprotein secreted throughout the mammalian gastrointestinal tract that can support endogenous microorganisms in the absence of complex polysaccharides. While several mucin-degrading bacteria have been identified, the interindividual differences in microbial communities capable of metabolizing this complex polymer are not well described. To determine whether community assembly on mucin is deterministic across individuals or whether taxonomically distinct but functionally similar mucin-degrading communities are selected across fecal inocula, we used a 10-day in vitro sequential batch culture fermentation from three human donors with mucin as the sole carbon source. For each donor, 16S rRNA gene amplicon sequencing was used to characterize microbial community succession, and the short-chain fatty acid profile was determined from the final community. All three communities reached a steady-state by day 7 in which the community composition stabilized. Taxonomic comparisons amongst communities revealed that one of the final communities had Desulfovibrio, another had Akkermansia, and all three shared other members, such as Bacteroides. Metabolic output differences were most notable for one of the donor's communities, with significantly less production of acetate and propionate than the other two communities. These findings demonstrate the feasibility of developing stable mucin-degrading communities with shared and unique taxa. Furthermore, the mechanisms and efficiencies of mucin degradation across individuals are important for understanding how this community-level process impacts human health.
Topics: Humans; Mucins; RNA, Ribosomal, 16S; Feces; Microbial Consortia; Fermentation; Bacteria; Fatty Acids, Volatile; Gastrointestinal Microbiome; Akkermansia; Desulfovibrio; Bacteroides
PubMed: 38794902
DOI: 10.1093/femsec/fiae078 -
Characterization of the Bottlenecks and Pathways for Inhibitor Dissociation from [NiFe] Hydrogenase.Journal of Chemical Information and... May 2024[NiFe] hydrogenases can act as efficient catalysts for hydrogen oxidation and biofuel production. However, some [NiFe] hydrogenases are inhibited by gas molecules...
[NiFe] hydrogenases can act as efficient catalysts for hydrogen oxidation and biofuel production. However, some [NiFe] hydrogenases are inhibited by gas molecules present in the environment, such as O and CO. One strategy to engineer [NiFe] hydrogenases and achieve O- and CO-tolerant enzymes is by introducing point mutations to block the access of inhibitors to the catalytic site. In this work, we characterized the unbinding pathways of CO in the complex with the wild-type and 10 different mutants of [NiFe] hydrogenase from using τ-random accelerated molecular dynamics (τRAMD) to enhance the sampling of unbinding events. The ranking provided by the relative residence times computed with τRAMD is in agreement with experiments. Extensive data analysis of the simulations revealed that from the two bottlenecks proposed in previous studies for the transit of gas molecules (residues 74 and 122 and residues 74 and 476), only one of them (residues 74 and 122) effectively modulates diffusion and residence times for CO. We also computed pathway probabilities for the unbinding of CO, O, and H from the wild-type [NiFe] hydrogenase, and we observed that while the most probable pathways are the same, the secondary pathways are different. We propose that introducing mutations to block the most probable paths, in combination with mutations to open the main secondary path used by H, can be a feasible strategy to achieve CO and O resistance in the [NiFe] hydrogenase from .
Topics: Hydrogenase; Molecular Dynamics Simulation; Carbon Monoxide; Desulfovibrio; Enzyme Inhibitors; Mutation; Oxygen; Protein Conformation
PubMed: 38728115
DOI: 10.1021/acs.jcim.4c00187 -
Frontiers in Insect Science 2024Building on our previous work, we investigate how dietary shifts affect gut microbial essential amino acid (EAA) provisioning in the lactating cockroach .
INTRODUCTION
Building on our previous work, we investigate how dietary shifts affect gut microbial essential amino acid (EAA) provisioning in the lactating cockroach .
METHOD
To that end, we fed cockroaches three distinct diets: a plant-only Gari diet composed of starchy and granulated root tuber Yucca (), a dog food diet (DF), and a cellulose-amended dog food (CADF) diet. We anticipated that the high carbohydrate, low protein Gari would highlight increased microbial EAA supplementation to the host.
RESULTS
By day 28, we observed distinct profiles of 14 bacterial families in the insect gut microbiomes of the three dietary groups. CADF-fed insects predominantly harbored cellulolytic and nitrogen-fixing bacteria families . In contrast, Gari-fed insects were enriched in anaerobic lignocellulolytic bacteria families and , while DF-fed insects had a prevalence of proteolytic anaerobes and sulfate-reducing bacteria . Furthermore, we confirmed significantly higher EAA supplementation in Gari-fed insects than in non-Gari-fed insects based on δC-EAA offsets between insect and their diets. The δC-EAA offsets between DF and CADF were nearly indistinguishable, highlighting the relevance of using the plant-based Gari in this experiment to unequivocally demonstrate this function in this insect. These results were underscored by lower standard metabolic rate (SMR) relative to the DF insect in Gari-fed (intermediate SMR and dietary quality) and CADF (least SMR and dietary quality) insects.
DISCUSSION
The influence of diet on EAA provisioning and SMR responses in insects underscores the need for further exploration into the role of gut microbial functions in modulating metabolic responses.
PubMed: 38711463
DOI: 10.3389/finsc.2024.1396984 -
Acta Crystallographica. Section F,... May 2024Molybdenum- or tungsten-dependent formate dehydrogenases have emerged as significant catalysts for the chemical reduction of CO to formate, with biotechnological...
Molybdenum- or tungsten-dependent formate dehydrogenases have emerged as significant catalysts for the chemical reduction of CO to formate, with biotechnological applications envisaged in climate-change mitigation. The role of Met405 in the active site of Desulfovibrio vulgaris formate dehydrogenase AB (DvFdhAB) has remained elusive. However, its proximity to the metal site and the conformational change that it undergoes between the resting and active forms suggests a functional role. In this work, the M405S variant was engineered, which allowed the active-site geometry in the absence of methionine S interactions with the metal site to be revealed and the role of Met405 in catalysis to be probed. This variant displayed reduced activity in both formate oxidation and CO reduction, together with an increased sensitivity to oxygen inactivation.
Topics: Desulfovibrio vulgaris; Formate Dehydrogenases; Catalytic Domain; Crystallography, X-Ray; Oxidation-Reduction; Models, Molecular; Formates; Carbon Dioxide; Bacterial Proteins
PubMed: 38699971
DOI: 10.1107/S2053230X24003911 -
Poultry Science Jul 2024Stress is known to disrupt the intestinal barrier and induce intestinal dysfunction. A critical role for gonadotropin inhibitory hormone (GnIH) in stress has emerged....
Stress is known to disrupt the intestinal barrier and induce intestinal dysfunction. A critical role for gonadotropin inhibitory hormone (GnIH) in stress has emerged. However, whether GnIH mediates stress-induced intestinal dysfunction remains unknown. The present study explored this question through in vivo and in vitro experiments in hens. Our in vivo experiments showed that continuous intraperitoneal injection of GnIH not only significantly increased the concentration of stress hormones in serum, but also significantly elevated the mRNA expression of glucocorticoid receptor (GR) in the duodenum and jejunum. Moreover, morphological and molecular analyses revealed that GnIH disrupted the physical and chemical barriers of the intestine and dramatically increased inflammatory factor levels in the intestine and serum of hens. Interestingly, the microbiomics results showed that GnIH altered the structure and composition of the gut flora in the cecum, revealing an increased abundance of harmful intestinal bacteria such as Desulfovibrionaceae. Similar results were found in in vitro studies in which the GnIH-induced intestinal mucosal barrier was disrupted, and inflammation increased in jejunal explants, although no significant difference was found in the expression of GR between the control and GnIH groups. Our results demonstrated that GnIH not only directly damaged intestinal barriers and elevated intestinal inflammation but also mediated stress and microflora imbalance-induced intestinal function disorder, suggesting that GnIH is a potential therapeutic target for gut dysfunction, stress-induced intestinal function disorder, and inflammatory bowel disease in animals and humans.
Topics: Animals; Chickens; Stress, Physiological; Female; Gastrointestinal Microbiome; Hypothalamic Hormones; Poultry Diseases; Avian Proteins; Intestinal Diseases
PubMed: 38697006
DOI: 10.1016/j.psj.2024.103757