-
Translational Psychiatry Mar 2021Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary...
Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genus Parabacteroides (P. distasonis and P. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereas Parabacteroides microbial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota "dysbiosis" in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.
Topics: Animals; Dietary Sugars; Gastrointestinal Microbiome; Memory; Neurodegenerative Diseases; Rats; Rats, Sprague-Dawley
PubMed: 33790226
DOI: 10.1038/s41398-021-01309-7 -
Frontiers in Cardiovascular Medicine 2021Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid...
Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid intima-media thickening, carotid plaque formation, and carotid stenosis. Accumulating evidence indicates that the gut microbiota plays an important role in CVD and gut-brain disorders, but the associations of the composition and metabolites of the gut microbiome with CAS have not been studied comprehensively. We performed a gut microbiome genome-wide association study in 31 patients with CAS and 51 healthy controls using whole-genome shotgun sequencing. We found that several risk factors (waist circumference, body mass index, diastolic blood pressure, systolic blood pressure, fasting blood glucose, glycated hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein cholesterol) and inflammatory markers (white blood cell count and absolute value of neutrophils) were significantly higher in the CAS group than in the control group. In addition, 21 species and 142 pathways were enriched in the CAS group, and 10 species and 1 pathway were enriched in the control group. Specifically, , and were the most abundant species in the CAS group, whereas , and were the most abundant species in the control group. Finally, we found that most gut microbes and microbial pathways that were enriched in the CAS group had significant positive correlations with clinical characteristics, whereas the microbes and pathways enriched in healthy controls had significant negative correlations with clinical characteristics excluding high-density lipoprotein cholesterol. In addition, the associations between gut microbes and some microbial pathways (short-chain fatty acid, lipopolysaccharide, and menaquinol biosynthesis) were identified. Our results indicate the existence of a cyclic pathway that elevates the circulating concentrations of trimethylamine-N-oxide in patients with CAS but reduces its concentrations in healthy controls.
PubMed: 34869642
DOI: 10.3389/fcvm.2021.739093 -
Frontiers in Immunology 2022infection is closely associated with various gastrointestinal diseases and poses a serious threat to human health owing to its increasing antimicrobial resistance....
infection is closely associated with various gastrointestinal diseases and poses a serious threat to human health owing to its increasing antimicrobial resistance. possesses two major virulence factors, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), which are involved in its pathogenesis. Probiotics have recently been used to eradicate infection and reduce the adverse effects of antibiotic-based therapies. MTS01 is a novel next-generation probiotic (NGP) with activities that can alleviate specific diseases by altering the gut microbiota. However, the mechanism by which MTS01 exerts its probiotic effects against infection remains unclear. Our results showed that administration of MTS01 to -infected model mice altered the composition of the gut microbiota and significantly reduced serum cholesterol levels, which mitigated -induced gastric inflammation. In addition, the pathogenic effects of VacA and CagA on gastric epithelial cells were markedly abrogated by treatment with MTS01. These results indicate that MTS01 can modulate gut microbiota composition and has anti-virulence factor functions, and thus could be developed as a novel functional probiotic for reducing -induced pathogenesis.
Topics: Animals; Anti-Bacterial Agents; Antigens, Bacterial; Bacteroidetes; Cholesterol; Cytotoxins; Gastrointestinal Microbiome; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Virulence Factors
PubMed: 35844600
DOI: 10.3389/fimmu.2022.916848 -
Hepatology (Baltimore, Md.) Apr 2022Hispanics are disproportionately affected by NAFLD, liver fibrosis, cirrhosis, and HCC. Preventive strategies and noninvasive means to identify those in this population...
BACKGROUND AND AIMS
Hispanics are disproportionately affected by NAFLD, liver fibrosis, cirrhosis, and HCC. Preventive strategies and noninvasive means to identify those in this population at high risk for liver fibrosis, are urgently needed. We aimed to characterize the gut microbiome signatures and related biological functions associated with liver fibrosis in Hispanics and identify environmental and genetic factors affecting them.
APPROACH AND RESULTS
Subjects of the population-based Cameron County Hispanic Cohort (CCHC; n = 217) were screened by vibration-controlled transient elastography (FibroScan). Among them, 144 (66.7%) had steatosis and 28 (13.0%) had liver fibrosis. The gut microbiome of subjects with liver fibrosis was enriched with immunogenic commensals (e.g., Prevotella copri, Holdemanella, Clostridiaceae 1) and depleted of Bacteroides caccae, Parabacteroides distasonis, Enterobacter, and Marinifilaceae. The liver fibrosis-associated metagenome was characterized by changes in the urea cycle, L-citrulline biosynthesis and creatinine degradation pathways, and altered synthesis of B vitamins and lipoic acid. These metagenomic changes strongly correlated with the depletion of Parabacteroides distasonis and enrichment of Prevotella and Holdemanella. Liver fibrosis was also associated with depletion of bacterial pathways related to L-fucose biosynthesis. Alcohol consumption, even moderate, was associated with high Prevotella abundance. The single-nucleotide polymorphisms rs3769502 and rs7573751 in the NCK adaptor protein 2 (NCK2) gene positively associated with high Prevotella abundance.
CONCLUSION
Hispanics with liver fibrosis display microbiome profiles and associated functional changes that may promote oxidative stress and a proinflammatory environment. These microbiome signatures, together with NCK2 polymorphisms, may have utility in risk modeling and disease prevention in this high-risk population.
Topics: Bacteroidetes; Carcinoma, Hepatocellular; Gastrointestinal Microbiome; Hispanic or Latino; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease
PubMed: 34633706
DOI: 10.1002/hep.32197 -
Frontiers in Microbiology 2022Insects have a long history of being used in medicine, with clear primary and secondary functions and less side effects, and the study and exploitation of medicinal...
Insects have a long history of being used in medicine, with clear primary and secondary functions and less side effects, and the study and exploitation of medicinal insects have received increasing attention. Insects gut microbiota and their metabolites play an important role in protecting the hosts from other potentially harmful microbes, providing nutrients, promoting digestion and degradation, and regulating growth and metabolism of the hosts. However, there are still few studies linking the medicinal values of insects with their gut microbes. In this study, we focused on the specific gut microbiota common to medicinal insects, hoping to trace the potential connection between medicinal values and gut microbes of medicinal insects. Based on 16S rRNA gene sequencing data, we compared the gut microbiota of medicinal insects [, () (Lewis) and ], in their medicinal stages, and non-medicinal insects ( L., , and ), and found that the intestinal microbial richness of medicinal insects was higher, and there were significant differences in the microbial community structure between the two groups. We established a model using a random-forest method to preliminarily screen out several types of gut microbiota common to medicinal insects that may play medicinal values: , , subsp. (), and . In particular, and were most probably involved in the anti-inflammatory effects of medicinal insects. Our results revealed an association between medicinal insects and their gut microbes, providing new development directions and possibly potential tools for utilizing microbes to enhance the medicinal efficacy of medicinal insects.
PubMed: 35651499
DOI: 10.3389/fmicb.2022.892767 -
Frontiers in Microbiology 2022Gut microbiota plays a critical role in the healthy growth and development of young animals. However, there are few studies on the gut microbiota of young Hainan black...
Gut microbiota plays a critical role in the healthy growth and development of young animals. However, there are few studies on the gut microbiota of young Hainan black goats. In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. The core phyla of the HW and LW groups were both and . , , and are the core genera of the HW group, and , , and are the core genera of the LW group. In addition, genera such as and , which were positively correlated with body weight, were enriched in the HW group; those genera, such as and , which were negatively correlated with body weight, were enriched in the LW group. Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth.
PubMed: 36187995
DOI: 10.3389/fmicb.2022.951473 -
Anaerobe Apr 2020Here, we sought to assess the levels of antibiotic resistance among intestinal Bacteroides and Parabacteroides strains collected between 2014 and 2016 in Europe and also...
Here, we sought to assess the levels of antibiotic resistance among intestinal Bacteroides and Parabacteroides strains collected between 2014 and 2016 in Europe and also attempted to compare resistance levels between clinical and commensal isolates. Bacteroides and Parabacteroides isolates were recovered from faecal samples via the novel Bacteroides Chromogenic Agar (BCA) method. Antibiotic susceptibilities were determined by agar dilution for ten antibiotics. The values obtained were then statistically evaluated. Altogether 202 Bacteroides/Parabacteroides isolates (of which 24, 11.9%, were B. fragilis) were isolated from the faecal specimens of individuals taken from five European countries. The percentage values of isolates resistant to ampicillin, amoxicillin/clavulanate, cefoxitin, imipenem, clindamycin, moxifloxacin, metronidazole, tetracycline, tigecycline and chloramphenicol were 96.6, 4.5, 14.9, 2.0, 47.3, 11.4, 0, 66.2, 1.5 and 0%, respectively. These values are close to those reported in the previous European clinical Bacteroides antibiotic susceptibility survey except for amoxicillin/clavulanate and clindamycin, where the former was lower and the latter was higher in normal microbiota isolates. To account for these latter findings and to assess temporal effects we compared the data specific for Hungary for the same period (2014-2016), and we found differences in the resistance rates for cefoxitin, moxifloxacin and tetracycline.
Topics: Anti-Bacterial Agents; Bacteroides; Bacteroides Infections; Drug Resistance, Microbial; Europe; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Microbial Sensitivity Tests; RNA, Ribosomal, 16S
PubMed: 32126280
DOI: 10.1016/j.anaerobe.2020.102182 -
Frontiers in Medicine 2022Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and...
Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and reveal potential mechanisms of frailty based on the integrated analysis of metabolome and gut microbiome. In this study, twenty subjects consisted of five middle-aged adults and fifteen older adults, of which fifteen older subjects were divided into three groups: non-frail, pre-frail, and frail, with five subjects in each group. The presence of frailty, pre-frailty, or non-frailty was established according to the physical frailty phenotype (PFP). We applied non-targeted metabolomics to serum and feces samples and used 16S rDNA gene sequencing to detect the fecal microbiome. The associations between metabolites and gut microbiota were analyzed by the Spearman's correlation analysis. Serum metabolic shifts in frailty mainly included fatty acids and derivatives, carbohydrates, and monosaccharides. Most of the metabolites belonging to these classes increased in the serum of frail older adults. Propylparaben was found to gradually decrease in non-frail, pre-frail, and frail older adults. Distinct changes in fecal metabolite profiles and gut microbiota were also found among middle-aged adults, non-frail and frail older subjects. The relative abundance of , , and decreased while the abundance of and increased in frailty. The above altered microbes were associated with the changed serum metabolites in frailty, which included dodecanedioic acid, D-ribose, D-(-)-mannitol, creatine and indole, and their related fecal metabolites. The changed microbiome and related metabolites may be used as the biomarkers of frailty and is worthy of further mechanistic studies.
PubMed: 35479954
DOI: 10.3389/fmed.2022.827174 -
International Journal of Cancer Oct 2020Colorectal cancer is a multifactorial disease involving inherited DNA mutations, environmental factors, gut inflammation and intestinal microbiota. Certain germline...
Colorectal cancer is a multifactorial disease involving inherited DNA mutations, environmental factors, gut inflammation and intestinal microbiota. Certain germline mutations within the DNA mismatch repair system are associated with Lynch syndrome tumors including right-sided colorectal cancer with mucinous phenotype and presence of an inflammatory infiltrate. Such tumors are more often associated with bacterial biofilms, which may contribute to disease onset and progression. Inflammatory bowel diseases are also associated with colorectal cancer and intestinal dysbiosis. Herein we addressed the question, whether inflammation can aggravate colorectal cancer development under mismatch repair deficiency. MSH2 mice were crossed into the IL-10 background to study the importance of inflammation and mucosal bacteria as a driver of tumorigenesis in a Lynch syndrome mouse model. An increase in large bowel tumorigenesis was found in double knockout mice both under conventional housing and under specific pathogen-free conditions. This increase was mostly due to the development of proximal tumors, a hotspot for tumorigenesis in Lynch syndrome, and was associated with a higher degree of inflammation. Additionally, bacterial invasion into the mucus of tumor crypts was observed in the proximal tumors. Inflammation shifted fecal and mucosal microbiota composition and was associated with enrichment in Escherichia-Shigella as well as Akkermansia, Bacteroides and Parabacteroides genera in fecal samples. Tumor-bearing double knockout mice showed a similar enrichment for Escherichia-Shigella and Parabacteroides. Lactobacilli, Lachnospiraceae and Muribaculaceae family members were depleted upon inflammation. In summary, chronic inflammation aggravates colonic tumorigenesis under mismatch repair deficiency and is associated with a shift in microbiota composition.
Topics: Animals; Bacteria; Biofilms; Carcinogenesis; Cell Transformation, Neoplastic; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mismatch Repair; Disease Models, Animal; Dysbiosis; Gastrointestinal Microbiome; Germ-Line Mutation; Inflammation; Interleukin-10; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Mice, Knockout
PubMed: 32350866
DOI: 10.1002/ijc.33028 -
Frontiers in Microbiology 2022β-glucuronidases (GUS) of intestinal bacteria remove glucuronic acid from glucoronides, reversing phase II metabolism of the liver and affecting the level of active...
β-glucuronidases (GUS) of intestinal bacteria remove glucuronic acid from glucoronides, reversing phase II metabolism of the liver and affecting the level of active deconjugated metabolites deriving from drugs or xenobiotics. Two hundred seventy-nine non-redundant GUS sequences are known in the gut microbiota, classified in seven structural categories (NL, L1, L2, mL1, mL2, mL1,2, and NC) with different biocatalytic properties. In the present study, the intestinal metagenome of 60 healthy subjects from five geographically different cohorts was assembled, binned, and mined to determine qualitative and quantitative differences in GUS profile, potentially affecting response to drugs and xenobiotics. Each metagenome harbored 4-70 different GUS, altogether accounting for 218. The amount of intestinal bacteria with at least one GUS gene was highly variable, from 0.7 to 82.2%, 25.7% on average. No significant difference among cohorts could be identified, except for the Ethiopia (ETH) cohort where GUS-encoding bacteria were significantly less abundant. The structural categories were differently distributed among the metagenomes, but without any statistical significance related to the cohorts. GUS profiles were generally dominated by the category NL, followed by mL1, L2, and L1. The GUS categories most involved in the hydrolysis of small molecules, including drugs, are L1 and mL1. Bacteria contributing to these categories belonged to , , , , , , , and . Bacteria harboring L1 GUS were generally scarcely abundant (<1.3%), except in three metagenomes, where they reached up to 24.3% for the contribution of and Bacteria harboring mL1 GUS were significantly more abundant (mean = 4.6%), with representing a major contributor. Albeit mL1 enzymes are less active than L1 ones, likely plays a pivotal role in the deglucuronidation, due to its remarkable abundance in the microbiomes. The observed broad interindividual heterogeneity of GUS profiles, particularly of the L1 and mL1 categories, likely represent a major driver of pharmacomicrobiomics variability, affecting drug response and toxicity. Different geographical origins, genetic, nutritional, and lifestyle features of the hosts seemed not to be relevant in the definition of glucuronidase activity, albeit they influenced the richness of the GUS profile.
PubMed: 35308380
DOI: 10.3389/fmicb.2022.826994