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Metabolites Apr 2023Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed with hyperactivity, impulsivity, and a lack of attention inconsistent with the...
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed with hyperactivity, impulsivity, and a lack of attention inconsistent with the patient's development level. The fact that people with ADHD frequently experience gastrointestinal (GI) dysfunction highlights the possibility that the gut microbiome may play a role in this condition. The proposed research aims to determine a biomarker for ADHD by reconstructing a model of the gut-microbial community. Genome-scale metabolic models (GEM) considering the relationship between gene-protein-reaction associations are used to simulate metabolic activities in organisms of gut. The production rates of dopamine and serotonin precursors and the key short chain fatty acids which affect the health status are determined under three diets (Western, Atkins', Vegan) and compared with those of healthy people. Elasticities are calculated to understand the sensitivity of exchange fluxes to changes in diet and bacterial abundance at the species level. The presence of Bacillota (genus and ), Actinobacteria (genus ), Bacteroidetes (genus ), and Bacteroidota (genus ) may be possible gut microbiota indicators of ADHD. This type of modeling approach taking microbial genome-environment interactions into account helps us understand the gastrointestinal mechanisms behind ADHD, and establish a path to improve the quality of life of ADHD patients.
PubMed: 37233633
DOI: 10.3390/metabo13050592 -
Microorganisms Jul 2023Gestational diabetes, affecting about 10% of pregnancies, is characterized by impaired glucose regulation and can lead to complications for health of pregnant women and... (Review)
Review
Gestational diabetes, affecting about 10% of pregnancies, is characterized by impaired glucose regulation and can lead to complications for health of pregnant women and their offspring. The microbiota, the resident microbes within the body, have been linked to the development of several metabolic conditions. This systematic review with meta-analysis aims to summarize the evidence on the differences in microbiota composition in pregnant women with gestational diabetes and their offspring compared to healthy pregnancies. A thorough search was conducted in the PubMed, Scopus, and Web of Science databases, and data from 21 studies were analyzed utilizing 41 meta-analyses. In the gut microbiota, Bifidobacterium and Alistipes were found to be more abundant in healthy pregnancies, while Roseburia appears to be more abundant in gestational diabetes. The heterogeneity among study findings regarding the microbiota in the meconium is considerable. The placental microbiota exhibited almost no heterogeneity, with an increased abundance of Firmicutes in the gestational diabetes group and a higher abundance of Proteobacteria in the control. The role of the microbiota in gestational diabetes is reinforced by these findings, which additionally point to the potential of microbiome-targeted therapies. To completely comprehend the interactions between gestational diabetes and the microbiome, standardizing methodologies and further research is necessary.
PubMed: 37512921
DOI: 10.3390/microorganisms11071749 -
Psychoneuroendocrinology Feb 2022Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory...
Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory can also be impaired by either chronic stress or microbiota imbalance. However, it remains to be established whether these could be a part of an integrated loop model and be responsible for memory impairments. To shed light on this, we used a two-pronged approach in Japanese quail: first stress-induced alterations in gut microbiota were characterized, then we tested whether this altered microbiota could affect brain and memory function when transferred to a germ-free host. The cecal microbiota of chronically stressed quails was found to be significantly different from that of unstressed individuals with lower α and β diversities and increased Bacteroidetes abundance largely represented by the Alistipes genus, a well-known stress target in rodents and humans. The transfer of this altered microbiota into germ-free quails decreased their spatial and cue-based memory abilities as previously demonstrated in the stressed donors. The recipients also displayed increased anxiety-like behavior, reduced basal plasma corticosterone levels and differential gene expression in the brain. Furthermore, cecal microbiota transfer from a chronically stressed individual was sufficient to mimic the adverse impact of chronic stress on memory in recipient hosts and this action may be related to the Alistipes genus. Our results provide evidence of a feed-forward loop system linking the microbiota-gut-brain axis to stress and memory function and suggest that maintaining a healthy microbiota could help alleviate memory impairments linked to chronic stress.
Topics: Animals; Anxiety; Corticosterone; Coturnix; Gastrointestinal Microbiome; Memory Disorders; Microbiota
PubMed: 34875421
DOI: 10.1016/j.psyneuen.2021.105594 -
Frontiers in Cellular and Infection... 2021Frailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal...
OBJECTIVE
Frailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome.
METHODS
We collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers.
RESULTS
Older adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of , , and and lower levels of the commensal genera , , , , and Spearman's correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. /, , , and were positively correlated with IL-6, while , , and were negatively correlated with IL-6. were found to be positively correlated with HGMB1. and were linked to the increased serum level of inflammatory factors and intestinal permeability.
CONCLUSIONS
Frailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.
Topics: Aged; Feces; Frailty; Gastrointestinal Microbiome; Humans; Microbiota; RNA, Ribosomal, 16S
PubMed: 34485176
DOI: 10.3389/fcimb.2021.696186 -
Genes & Nutrition Jan 2022Previous observational studies have demonstrated inconsistent and inconclusive results of changes in the intestinal microbiota in patients with obesity and metabolic... (Review)
Review
BACKGROUND
Previous observational studies have demonstrated inconsistent and inconclusive results of changes in the intestinal microbiota in patients with obesity and metabolic disorders. We performed a systematic review to explore evidence for this association across different geography and populations.
METHODS
We performed a systematic search of MEDLINE (OvidSP) and Embase (OvidSP) of articles published from Sept 1, 2010, to July 10, 2021, for case-control studies comparing intestinal microbiome of individuals with obesity and metabolic disorders with the microbiome of non-obese, metabolically healthy individuals (controls). The primary outcome was bacterial taxonomic changes in patients with obesity and metabolic disorders as compared to controls. Taxa were defined as "lean-associated" if they were depleted in patients with obesity and metabolic disorders or negatively associated with abnormal metabolic parameters. Taxa were defined as "obesity-associated" if they were enriched in patients with obesity and metabolic disorders or positively associated with abnormal metabolic parameters.
RESULTS
Among 2390 reports screened, we identified 110 full-text articles and 60 studies were included. Proteobacteria was the most consistently reported obesity-associated phylum. Thirteen, nine, and ten studies, respectively, reported Faecalibacterium, Akkermansia, and Alistipes as lean-associated genera. Prevotella and Ruminococcus were obesity-associated genera in studies from the West but lean-associated in the East. Roseburia and Bifidobacterium were lean-associated genera only in the East, whereas Lactobacillus was an obesity-associated genus in the West.
CONCLUSIONS
We identified specific bacteria associated with obesity and metabolic disorders in western and eastern populations. Mechanistic studies are required to determine whether these microbes are a cause or product of obesity and metabolic disorders.
PubMed: 35093025
DOI: 10.1186/s12263-021-00703-6 -
EBioMedicine May 2023Atrial fibrillation (AF) is an important heart rhythm disorder in aging populations. The gut microbiome composition has been previously related to cardiovascular disease...
BACKGROUND
Atrial fibrillation (AF) is an important heart rhythm disorder in aging populations. The gut microbiome composition has been previously related to cardiovascular disease risk factors. Whether the gut microbial profile is also associated with the risk of AF remains unknown.
METHODS
We examined the associations of prevalent and incident AF with gut microbiota in the FINRISK 2002 study, a random population sample of 6763 individuals. We replicated our findings in an independent case-control cohort of 138 individuals in Hamburg, Germany.
FINDINGS
Multivariable-adjusted regression models revealed that prevalent AF (N = 116) was associated with nine microbial genera. Incident AF (N = 539) over a median follow-up of 15 years was associated with eight microbial genera with false discovery rate (FDR)-corrected P < 0.05. Both prevalent and incident AF were associated with the genera Enorma and Bifidobacterium (FDR-corrected P < 0.001). AF was not significantly associated with bacterial diversity measures. Seventy-five percent of top genera (Enorma, Paraprevotella, Odoribacter, Collinsella, Barnesiella, Alistipes) in Cox regression analyses showed a consistent direction of shifted abundance in an independent AF case-control cohort that was used for replication.
INTERPRETATION
Our findings establish the basis for the use of microbiome profiles in AF risk prediction. However, extensive research is still warranted before microbiome sequencing can be used for prevention and targeted treatment of AF.
FUNDING
This study was funded by European Research Council, German Ministry of Research and Education, Academy of Finland, Finnish Medical Foundation, and the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, and the Paavo Nurmi Foundation.
Topics: Humans; Atrial Fibrillation; Gastrointestinal Microbiome; Heart; Bacteria; Aging; Incidence
PubMed: 37119735
DOI: 10.1016/j.ebiom.2023.104583 -
NPJ Biofilms and Microbiomes Apr 2023The composition of the gut microbiome was previously found to be associated with clinical responses to dyslipidemia, but there is limited consensus on the dynamic change...
The composition of the gut microbiome was previously found to be associated with clinical responses to dyslipidemia, but there is limited consensus on the dynamic change of the gut microbiota during pregnancy and the specific microbiome characteristics linked to dyslipidemia in pregnant women. We collected fecal samples from 513 pregnant women at multiple time points during pregnancy in a prospective cohort. Taxonomic composition and functional annotations were determined by 16S rRNA amplicon sequencing and shotgun metagenomic sequencing. The predictive potential of gut microbiota on the risk of dyslipidemia was determined. The gut microbiome underwent dynamic changes during pregnancy, with significantly lower alpha diversity observed in dyslipidemic patients compared to their healthy counterparts. Several genera, including Bacteroides, Paraprevotella, Alistipes, Christensenellaceae R7 group, Clostridia UCG-014, and UCG-002 were negatively associated with lipid profiles and dyslipidemia. Further metagenomic analysis recognized a common set of pathways involved in gastrointestinal inflammation, where disease-specific microbes played an important role. Machine learning analysis confirmed the link between the microbiome and its progression to dyslipidemia, with a micro-averaged AUC of 0.824 (95% CI: 0.782-0.855) combined with blood biochemical data. Overall, the human gut microbiome, including Alistipes and Bacteroides, was associated with the lipid profile and maternal dyslipidemia during pregnancy by perturbing inflammatory functional pathways. Gut microbiota combined with blood biochemical data at the mid-pregnancy stage could predict the risk of dyslipidemia in late pregnancy. Therefore, the gut microbiota may represent a potential noninvasive diagnostic and therapeutic strategy for preventing dyslipidemia in pregnancy.
Topics: Humans; Pregnancy; Female; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Prospective Studies; Microbiota; Bacteroidetes; Lipids
PubMed: 37012285
DOI: 10.1038/s41522-023-00383-7 -
Gut Microbes Dec 2023Low molecular weight (6.5 kDa) polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut...
Low molecular weight (6.5 kDa) polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4, CD8 T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including , , , , and , and reduced the abundance of and CTX-derived bacteria (, , , and ). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.
Topics: Gastrointestinal Microbiome; Molecular Weight; Polysaccharides; Glycyrrhiza; Immunity
PubMed: 37948152
DOI: 10.1080/19490976.2023.2276814 -
Frontiers in Medicine 2023Gut dysbiosis is believed to be one of the several mechanisms that are involved in the pathogenesis of gout. This systematic review aimed to summarize the role of gut...
OBJECTIVES
Gut dysbiosis is believed to be one of the several mechanisms that are involved in the pathogenesis of gout. This systematic review aimed to summarize the role of gut dysbiosis in gout disease and uncover the underlying mechanisms.
METHODS
A comprehensive search was conducted on PubMed, Web of Science, and Scopus databases up to October 2021. Animal studies and human observational studies, including case-control, cross-sectional, and cohort studies assessing the association between gut microbiota composition and gout were included. The quality of included studies has been evaluated using the Newcastle-Ottawa Quality Assessment scale (NOS) and the SYRCLE's risk of bias tool.
RESULTS
Initially, we found 274 studies among which 15 studies were included in this systematic review. Of them, 10 studies were conducted on humans and 5 studies were conducted on animals. Increased abundance of and decreased abundance of alters purine metabolism, thereby aggravating gout condition. Moreover, a higher abundance of and in gout modulates enzymatic activity in purine metabolism. Butyrate-producing bacteria such as , and have higher abundance in healthy controls compared to gout patients, suggesting the anti-inflammatory and anti-microbial role of short-chain fatty acids (SCFAs). Lipopolysaccharides (LPS)-releasing bacteria, such as e, , and , are also involved in the pathogenesis of gout disease by stimulating the innate immune system.
CONCLUSION
Exploring the role of gut dysbiosis in gout and the underlying mechanisms can help develop microbiota-modulating therapies for gout.
PubMed: 37265486
DOI: 10.3389/fmed.2023.1163778 -
American Journal of Transplantation :... Feb 2023Intestinal commensals can exert immunomodulatory effects on the host, with beneficial or detrimental consequences depending on underlying diseases. We have previously...
Intestinal commensals can exert immunomodulatory effects on the host, with beneficial or detrimental consequences depending on underlying diseases. We have previously correlated longer survival of minor mismatched skin grafts in mice with the presence of an intestinal commensal bacterium, Alistipes onderdonkii. In this study, we investigated its sufficiency and mechanism of action. Oral administration of A onderdonkii strain DSM19147 but not DSM108265 was sufficient to prolong minor mismatched skin graft survival through inhibition of tumor necrosis factor production. Through metabolomic and metagenomic comparisons between DSM19147 and DSM108265, we identified candidate gene products associated with the anti-inflammatory effect of DSM19147. A onderdonkii DSM19147 can lower inflammation both at a steady state and after transplantation and may serve as an anti-inflammatory probiotic beneficial for transplant recipients.
Topics: Animals; Mice; Administration, Oral; Allografts; Graft Rejection; Graft Survival; Mice, Inbred BALB C; Mice, Inbred C57BL; Skin Transplantation; Transplantation, Homologous; Bacteroidetes; Probiotics
PubMed: 36804134
DOI: 10.1016/j.ajt.2022.11.011