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GeroScience Apr 2024Microbiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to...
Microbiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to examine the associations between microbiota composition and measures of function, such as a composite measure of physical capacity, and biological age in midlife, prior to onset of age-related diseases. Seventy healthy midlife individuals (age 44.58 ± 0.18) were examined cross-sectionally, and their gut-microbiota profile was characterized from stool samples using 16SrRNA gene sequencing. Biological age was measured using the Klemera-Doubal method and a composition of blood and physiological biomarkers. Physical capacity was calculated based on sex-standardized functional tests. We demonstrate that the women had significantly richer microbiota, p = 0.025; however, microbiota diversity was not linked with chronological age, biological age, or physical capacity for either women or men. Men had slightly greater β-diversity; however, β-diversity was positively associated with biological age and with physical capacity for women only (p = 0.01 and p = 0.04; respectively). For women, an increase in abundance of Roseburia faecis and Collinsella aerofaciens, as well as genus Ruminococcus and Dorea, was significantly associated with higher biological age and lower physical capacity; an increase in abundance of Akkermansia muciniphila and genera Bacteroides and Alistipes was associated with younger biological age and increased physical capacity. Differentially abundant taxa were also associated with non-communicable diseases. These findings suggest that microbiota composition is a potential mechanism linking physical capacity and health status; personalized probiotics may serve as a new means to support health-promoting interventions in midlife. Investigating additional factors underlying this link may facilitate the development of a more accurate method to estimate the rate of aging.
Topics: Humans; Male; Female; Sex Characteristics; Gastrointestinal Microbiome; Exercise; Aging
PubMed: 37610596
DOI: 10.1007/s11357-023-00905-3 -
Investigative Ophthalmology & Visual... May 2024To identify compositional differences in the gut microbiome of nonmyopes (NM) and myopes using 16S ribosomal RNA sequencing and to investigate whether the microbiome may...
PURPOSE
To identify compositional differences in the gut microbiome of nonmyopes (NM) and myopes using 16S ribosomal RNA sequencing and to investigate whether the microbiome may contribute to the onset or progression of the condition.
METHODS
Faecal samples were collected from 52 adult participants, of whom 23 were NM, 8 were progressive myopes (PM), and 21 were stable myopes (SM). The composition of the gut microbiota in each group was analysed using 16S ribosomal RNA gene sequencing.
RESULTS
There were no significant differences in alpha and beta diversity between the three groups (NM, PM, and SM). However, the distributions of Bifidobacterium, Bacteroides, Megamonas, Faecalibacterium, Coprococcus, Dorea, Roseburia, and Blautia were significantly higher in the myopes (SM and PM combined) when compared with emmetropes. The myopes exhibited significantly greater abundance of bacteria that are linked to the regulation of dopaminergic signalling, such as Clostridium, Ruminococcus, Bifidobacterium, and Bacteroides. Individuals with stable myopia were found to have a significantly higher proportion of Prevotella copri than those with progressive myopia. Bifidobacterium adolescentis, a gamma-aminobutyric acid (GABA)-producing bacterium, was significantly higher in all myopes than in NM and, in the comparison between SM and PM, it is significantly higher in SM. B. uniformis and B. fragilis, both GABA-producing Bacteroides, were present in relatively high abundance in all myopes and in SM compared with PM, respectively.
CONCLUSIONS
The presence of bacteria related to dopamine effect and GABA-producing bacteria in the gut microbiome of myopes may suggest a role of these microorganisms in the onset and progression of myopia.
Topics: Humans; Male; Adult; Female; Gastrointestinal Microbiome; Feces; RNA, Ribosomal, 16S; Myopia; Bacteria; Young Adult; Middle Aged; DNA, Bacterial
PubMed: 38691091
DOI: 10.1167/iovs.65.5.2 -
Translational Psychiatry Jan 2024The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal...
BACKGROUND
The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR).
METHODS
The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD's causal effects on the relative abundances of specific features of the gut microbiome.
RESULTS
In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability.
CONCLUSION
Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
Topics: Humans; Gastrointestinal Microbiome; Stress Disorders, Post-Traumatic; Genome-Wide Association Study; Reproducibility of Results; Dietary Supplements
PubMed: 38296956
DOI: 10.1038/s41398-024-02765-7 -
The Journal of Clinical Endocrinology... Feb 2024Compared with the relatively benign effects of increased subcutaneous adipose tissue (SAT), increased visceral adipose tissue (VAT) volume is a causal risk factor for... (Observational Study)
Observational Study
CONTEXT
Compared with the relatively benign effects of increased subcutaneous adipose tissue (SAT), increased visceral adipose tissue (VAT) volume is a causal risk factor for hypertension, hyperlipidemia, type 2 diabetes, and cardiovascular disease. In rodents, increased VAT volume and triglyceride density and ectopic lipid accumulation in kidneys and liver have been induced by alterations in the gut microbiome. However, few studies have characterized these relationships in humans.
OBJECTIVE
To evaluate the tissue triglyceride content of VAT and SAT, liver, kidneys, and pancreas in male and female adults and assess associations with markers of glucose tolerance, serum insulin, and lipids and characteristics of the gut microbiome.
METHODS
Cross-sectional observational study of healthy human adults (n = 60) at a clinical research center. Body mass index (BMI), body composition, and oral glucose tolerance were assessed. Microbiome analysis was conducted on stool samples using 16S rRNA v3 amplicon sequencing. The triglyceride content of VAT, SAT, liver, kidney and pancreas were determined by assessing proton density fat fraction (PDFF) with magnetic resonance imaging (MRI).
RESULTS
Higher VAT PDFF and the ratio of VAT to SAT PDFF were related to higher BMI, HbA1c, HOMA-IR, non-high-density lipoprotein cholesterol, plasma triglycerides, low-density lipoprotein (LDL) cholesterol, and lower high-density lipoprotein (HDL) cholesterol. A higher VAT PDFF and VAT to SAT PDFF ratio were associated with lower alpha diversity and altered beta diversity of the gut microbiome. Differences in VAT were associated with higher relative abundance of the phylum Firmicutes, lower relative abundance of the phylum Bacteroidetes, and enrichment of the bacterial genera Dorea, Streptococcus, and Solobacterium.
CONCLUSION
VAT PDFF measured with MRI is related to impaired glucose homeostasis, dyslipidemia, and differences in the gut microbiome, independently of the total body fat percentage.
Topics: Adult; Humans; Male; Female; Intra-Abdominal Fat; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Cross-Sectional Studies; RNA, Ribosomal, 16S; Triglycerides; Cholesterol, HDL; Glucose; Adipose Tissue
PubMed: 37837606
DOI: 10.1210/clinem/dgad604 -
Environmental Research Jun 2021This review covers a wide body of literature to gain an understanding of the impacts of informal activities related to metal extraction (primary mining and recycling) on... (Review)
Review
Neurodevelopment and exposure to neurotoxic metal(loid)s in environments polluted by mining, metal scrapping and smelters, and e-waste recycling in low and middle-income countries.
This review covers a wide body of literature to gain an understanding of the impacts of informal activities related to metal extraction (primary mining and recycling) on early life exposure to neurotoxicants and on neurodevelopment. In primary mining, gold extraction with Hg amalgamation is the main environmental cause of Hg pollution in most artisanal small-scale gold mining (ASGM) activities around the world. Nevertheless, in Sub-Saharan Africa (SSA), Pb disrupted from gold-related ores, mining, and artisanal cookware production are an important neurotoxicant that seriously contaminates the affected population, with devastating effects on children. In e-waste recycling settings, the range of neurotoxic substances that contaminate mothers and children is wider than in primary mining environments. Thus, Hg and Pb are major pre- and postnatal neurotoxicants affecting children in the informal metal extraction activities and SSA countries show the highest record of human contamination and of neurotoxic effects on children. There are additional sources of neurotoxic contamination from mining and metal processing activities (cyanide tailing in South America and SSA) and/or co-exposure to Hg-containing products such as cosmetics (soaps and Hg-based skin lightning creams in Africa) and pediatric Thimerosal-containing vaccines (TCVs, that breaks down to ethyl-mercury) in current use in middle and low income countries. However, the action of these neurotoxicants (per se or in combination) on children needs more attention and research. Studies show a negative association between biomarkers of all environmental metal(loid)s (As, Cd, Hg, Mn, and Pb) studied and neurodevelopment in young children. Sadly, in many unregulated activities, child labor is widely employed, thus presenting an additional occupational exposure. Children living in polluted environments related to metal processing are disproportionately exposed to a wide range of co-occurring neurotoxic substances. The review showed compelling evidence from highly representative parts of the world (Africa, Asia, and Latin America) that the studied neurotoxic substances negatively affected areas of the brain associated with language, memory and executive function, as well as psychosocial behavior. Protecting the environment and children from unregulated and highly polluting metal extraction and processing are inextricably intertwined and deserve urgent attention.
Topics: Africa; Asia; Child; Child, Preschool; Developing Countries; Electronic Waste; Environmental Monitoring; Gold; Humans; Latin America; Mercury
PubMed: 33861977
DOI: 10.1016/j.envres.2021.111124 -
Frontiers in Cellular and Infection... 2023The transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge...
BACKGROUND
The transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge gap if gut microbiota (GM) play a role in differing MCU from MA use disorder (MUD). We aimed to investigate the clinical features and GM differences between individuals with MCU and MUD.
METHOD
We recruited two groups of MA users -MCU and MUD - and matched them according to age and body mass index (n=21 in each group). Participants were accessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, and their fecal samples were undergone 16S ribosomal DNA sequencing. We compared the hosts' clinical features and GM diversity, composition, and structure (represented by enterotypes) between the two groups. We have identified differential microbes between the two groups and performed network analyses connecting GM and the clinical traits.
RESULT
Compared with the casual users, individuals with MUD had higher incidences of MA-induced neuropsychiatric symptoms (e.g., paranoia, depression) and withdrawal symptoms (e.g., fatigue, drowsiness, and increased appetite), as well as stronger cravings for and intentions to use MA, and increased MA tolerance. The GM diversity showed no significant differences between the two groups, but four genera (Halomonas, Clostridium, Devosia, and Dorea) were enriched in the individuals with MUD (p<0.05). Three distinct enterotypes were identified in all MA users, and Ruminococcus-driven enterotype 2 was dominant in individuals with MUD compared to the MCU (61.90% vs. 28.60%, p=0.03). Network analysis shows that Devosia is the hub genus (hub index = 0.75), which is not only related to the counts of the MUD diagnostic criteria (ρ=0.40; p=0.01) but also to the clinical features of MA users such as reduced social activities (ρ=0.54; p<0.01). Devosia is also associated with the increased intention to use MA (ρ=0.48; p<0.01), increased MA tolerance (ρ=0.38; p=0.01), craving for MA (ρ=0.37; p=0.01), and MA-induced withdrawal symptoms (p<0.05).
CONCLUSION
Our findings suggest that Ruminococcus-driven enterotype 2 and the genera Devosia might be two influential factors that differentiate MA casual use from MUD, but further studies are warranted.
Topics: Humans; Methamphetamine; Gastrointestinal Microbiome; Substance Withdrawal Syndrome; Amphetamine-Related Disorders; Appetite
PubMed: 36909722
DOI: 10.3389/fcimb.2023.1103919 -
Kidney & Blood Pressure Research 2023Numerous research works have shown that serum Gal-deficient (Gd) IgA1 levels are increased in IgA nephropathy (IgAN) patients and these levels are a dangerous risk...
INTRODUCTION
Numerous research works have shown that serum Gal-deficient (Gd) IgA1 levels are increased in IgA nephropathy (IgAN) patients and these levels are a dangerous risk factor for IgAN. A relationship between the gut microbiota and IgAN has been reported. Whether the gut microbiota participates in the pathogenesis of IgAN was still controversial.
METHODS
We evaluated changes in the gut flora and the levels of Gd-IgA1 in IgAN patients and healthy controls (HCs). We investigated the Gd-IgA1 levels in both blood and urine specimens. C57BL/6 mice were given a broad-spectrum antibiotic cocktail to deplete the endogenous gut flora. We established a model of IgAN in pseudosterile mice and investigated the expression of the markers of intestinal permeability, inflammation, and local immune responses.
RESULTS
Studies have shown that the levels of certain gut flora differ between IgAN patients and HCs. Moreover, elevated Gd-IgA1 levels were found in both the serum and urine. Interestingly, Coprococcus, Dorea, Bifidobacterium, Blautia, and Lactococcus, selected from 10 candidate biomarkers to predict risk in IgAN patients according to random forest analysis, were inversely associated with urinary Gd-IgA1 levels. Notably, the urine level of Gd-IgA1 could best distinguish IgAN patients from HCs. Additionally, the degree of kidney damage in pseudosterile mice with IgAN was more severe than that in mice with IgAN. Furthermore, the markers of intestinal permeability were significantly elevated in pseudosterile IgAN mice. Moreover, the inflammation responses (TLR4, MyD88, and NF-κB in intestinal and renal tissues; TNF-α and IL-6 in serum) and local immune responses (BAFF and APRIL in intestinal tissue) were upregulated in pseudosterile IgAN mice.
CONCLUSIONS
The urine Gd-IgA1 level may be as a biomarker for the early screening of potential IgAN, and gut microbiota dysbiosis was demonstrated in IgAN, which might involve the dysfunction of the mucosal barrier, inflammation, and local immune responses.
Topics: Humans; Animals; Mice; Glomerulonephritis, IGA; Gastrointestinal Microbiome; Mice, Inbred C57BL; Immunoglobulin A; Inflammation; Biomarkers; Immunity
PubMed: 36878203
DOI: 10.1159/000528973 -
Frontiers in Cellular and Infection... 2022Due to decreased immunity, both antibiotics and antifungals are regularly used in pediatric hematologic-cancer patients as a means to prevent severe infections and...
Antibiotic and antifungal use in pediatric leukemia and lymphoma patients are associated with increasing opportunistic pathogens and decreasing bacteria responsible for activities that enhance colonic defense.
Due to decreased immunity, both antibiotics and antifungals are regularly used in pediatric hematologic-cancer patients as a means to prevent severe infections and febrile neutropenia. The general effect of antibiotics on the human gut microbiome is profound, yielding decreased diversity and changes in community structure. However, the specific effect on pediatric oncology patients is not well-studied. The effect of antifungal use is even less understood, having been studied only in mouse models. Because the composition of the gut microbiome is associated with regulation of hematopoiesis, immune function and gastrointestinal integrity, changes within the patient gut can have implications for the clinical management of hematologic malignancies. The pediatric population is particularly challenging because the composition of the microbiome is age dependent, with some of the most pronounced changes occurring in the first three years of life. We investigated how antibiotic and antifungal use shapes the taxonomic composition of the stool microbiome in pediatric patients with leukemia and lymphoma, as inferred from both 16S rRNA and metagenome data. Associations with age, antibiotic use and antifungal use were investigated using multiple analysis methods. In addition, multivariable differential abundance was used to identify and assess specific taxa that were associated with multiple variables. Both antibiotics and antifungals were linked to a general decline in diversity in stool samples, which included a decrease in relative abundance in butyrate producers that play a critical role in host gut physiology (, , ),. Furthermore, antifungal use was associated with a significant increase in relative abundance of opportunistic pathogens. Collectively, these findings have important implications for the treatment of leukemia and lymphoma patients. Butyrate is important for gastrointestinal integrity; it inhibits inflammation, reinforces colonic defense, mucosal immunity. and decreases oxidative stress. The routine use of broad-spectrum anti-infectives in pediatric oncology patients could simultaneously contribute to a decline in gastrointestinal integrity and colonic defense while promoting increases in opportunistic pathogens within the patient gut. Because the gut microbiome has been linked to both short-term clinical outcomes, and longer-lasting health effects, systematic characterization of the gut microbiome in pediatric patients during, and beyond, treatment is warranted.
Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Butyrates; Child; Child, Preschool; Humans; Leukemia; Lymphoma; Mice; RNA, Ribosomal, 16S
PubMed: 35967843
DOI: 10.3389/fcimb.2022.924707 -
Scientific Reports Oct 2023Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis...
Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis.
Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera (Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger) and one fungal genus (Malassezia furfur) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.
Topics: Humans; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Dysbiosis; Propionates; Multiomics; Metabolomics; Bacteria; Eating; Hydroxybutyrates
PubMed: 37863978
DOI: 10.1038/s41598-023-45066-7 -
Heart & Lung : the Journal of Critical... 2024Multiple studies have highlighted a potential link between gut microbes and the onset of Pulmonary Arterial Hypertension (PAH). Nonetheless, the precise cause-and-effect...
BACKGROUND
Multiple studies have highlighted a potential link between gut microbes and the onset of Pulmonary Arterial Hypertension (PAH). Nonetheless, the precise cause-and-effect relationship remains uncertain.
OBJECTIVES
In this investigation, we utilized a two-sample Mendelian randomization (TSMR) approach to probe the presence of a causal connection between gut microbiota and PAH.
METHODS
Genome-wide association (GWAS) data for gut microbiota and PAH were sourced from MiBioGen and FinnGen research, respectively. Inverse variance weighting (IVW) was used as the primary method to explore the causal effect between gut flora and PAH, supplemented by MR-Egger, weighted median (WM). Sensitivity analyses examined the robustness of the MR results. Reverse MR analysis was used to rule out the effect of reverse causality on the results.
RESULTS
The results indicate that Genus Ruminococcaceae UCG004 (OR = 0.407, P = 0.031) and Family Alcaligenaceae (OR = 0.244, P = 0.014) were protective factors for PAH. Meanwhile Genus Lactobacillus (OR = 2.446, P = 0.013), Class Melainabacteria (OR = 2.061, P = 0.034), Phylum Actinobacteria (OR = 3.406, P = 0.010), Genus Victivallis (OR = 1.980, P = 0.010), Genus Dorea (OR = 3.834, P = 0.024) and Genus Slackia (OR = 2.622, P = 0.039) were associated with an increased Prevalence of PAH. Heterogeneity and pleiotropy were not detected by sensitivity analyses, while there was no reverse causality for these nine specific gut microorganisms.
CONCLUSIONS
This study explores the causal effects of eight gut microbial taxa on PAH and provides new ideas for early prevention of PAH.
Topics: Humans; Pulmonary Arterial Hypertension; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Familial Primary Pulmonary Hypertension
PubMed: 38290183
DOI: 10.1016/j.hrtlng.2024.01.002