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Nature Medicine Nov 2023Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise,...
Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise, metagenome-wide association studies (MWASs) between bacterial SNPs and human traits can suggest mechanistic links, but very few such studies have been done thus far. In this study, we devised an MWAS framework to detect SNPs and associate them with host phenotypes systematically. We recruited and obtained gut metagenomic samples from a cohort of 7,190 healthy individuals and discovered 1,358 statistically significant associations between a bacterial SNP and host body mass index (BMI), from which we distilled 40 independent associations. Most of these associations were unexplained by diet, medications or physical exercise, and 17 replicated in a geographically independent cohort. We uncovered BMI-associated SNPs in 27 bacterial species, and 12 of them showed no association by standard relative abundance analysis. We revealed a BMI association of an SNP in a potentially inflammatory pathway of Bilophila wadsworthia as well as of a group of SNPs in a region coding for energy metabolism functions in a Faecalibacterium prausnitzii genome. Our results demonstrate the importance of considering nucleotide-level diversity in microbiome studies and pave the way toward improved understanding of interpersonal microbiome differences and their potential health implications.
Topics: Humans; Gastrointestinal Microbiome; Body Mass Index; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Microbiota; Bacteria
PubMed: 37919437
DOI: 10.1038/s41591-023-02599-8 -
Frontiers in Cardiovascular Medicine 2023The pathogenesis of hypertension involves a diverse range of genetic, environmental, hemodynamic, and more causative factors. Recent evidence points to an association...
BACKGROUND & AIMS
The pathogenesis of hypertension involves a diverse range of genetic, environmental, hemodynamic, and more causative factors. Recent evidence points to an association between the gut microbiome and hypertension. Given that the microbiota is in part determined by host genetics, we used the two-sample Mendelian randomization (MR) analysis to address the bidirectional causal link between gut microbiota and hypertension.
METHODS
We selected genetic variants ( < 1 × 10) for gut microbiota ( = 18,340) from the MiBioGen study. Genetic association estimates for hypertension were extracted from genome-wide association study (GWAS) summary statistics on 54,358 cases and 408,652 controls. Seven complementary MR methods were implemented, including the inverse-variance weighted (IVW) method, followed by sensitivity analyses to verify the robustness of the results. Reverse-direction MR analyses were further conducted to probe if there was a reverse causative relationship. Bidirectional MR analysis then examines a modulation of gut microbiota composition by hypertension.
RESULTS
At the genus level, our MR estimates from gut microbiome to hypertension showed that there were 5 protective factors , , , and (id.1000000073), while 6 genera , , , , , and (id.2041) are risk factors. The and were detrimental and beneficial at the family level, respectively. In contrast, the MR results of hypertension-gut flora showed hypertensive states can lead to an increased abundance of E, , and and a lower abundance of , , , and .
CONCLUSION
Altered gut microbiota is a causal factor in the development of hypertension, and hypertension causes imbalances in the intestinal flora. Substantial research is still needed to find the key gut flora and explore the specific mechanisms of their effects so that new biomarkers can be found for blood pressure control.
PubMed: 37215554
DOI: 10.3389/fcvm.2023.1167346 -
Nutrients Dec 2022Probiotics could improve cognitive functions in patients with neurological disorders such as Alzheimer’s disease, but the effects on cognitive function in healthy... (Randomized Controlled Trial)
Randomized Controlled Trial
Probiotics could improve cognitive functions in patients with neurological disorders such as Alzheimer’s disease, but the effects on cognitive function in healthy older adults without cognitive impairment need further study. The purpose of this study was to investigate the effect of Bifidobacterium longum BB68S (BB68S) on cognitive functions among healthy older adults without cognitive impairment. A randomized, double-blind, placebo-controlled trial was conducted with 60 healthy older adults without cognitive impairment who were divided into probiotic or placebo groups and required to consume either a sachet of probiotic (BB68S, 5 × 1010 CFU/sachet) or placebo once daily for 8 weeks. The Montreal Cognitive Assessment (MoCA) was used as an inclusion screening tool to screen elderly participants with healthy cognitive function in our study, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function in subjects before and after intervention as an assessment tool. BB68S significantly improved subjects’ cognitive functions (total RBANS score increased by 18.89 points after intervention, p < 0.0001), especially immediate memory, visuospatial/constructional, attention, and delayed memory domains. BB68S intervention increased the relative abundances of beneficial bacteria Lachnospira, Bifidobacterium, Dorea, and Cellulosilyticum, while decreasing those of bacteria related to cognition impairment, such as Collinsella, Parabacteroides, Tyzzerella, Bilophila, unclassified_c_Negativicutes, Epulopiscium, Porphyromonas, and Granulicatella. In conclusion, BB68S could improve cognitive functions in healthy elderly adults without cognitive impairment, along with having beneficial regulatory effects on their gut microbiota. This study supports probiotics as a strategy to promote healthy aging and advances cognitive aging research.
Topics: Humans; Aged; Bifidobacterium longum; Probiotics; Cognition; Bifidobacterium; Cognitive Dysfunction; Double-Blind Method
PubMed: 36615708
DOI: 10.3390/nu15010051 -
Frontiers in Endocrinology 2022As a metabolic disease, one important feature of non-alcoholic fatty liver disease (NAFLD) is the disturbance of the intestinal flora. Spleen-strengthening and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
As a metabolic disease, one important feature of non-alcoholic fatty liver disease (NAFLD) is the disturbance of the intestinal flora. Spleen-strengthening and liver-draining formula (SLF) is a formula formed according to the theory of "One Qi Circulation" (Qing Dynasty, 1749) of Traditional Chinese Medicine (TCM), which has shown significant therapeutic effect in patients with NAFLD in a preliminary clinical observation. In this study, we aim to explore the mechanism of SLF against NAFLD, especially its effect on glucolipid metabolism, from the perspective of intestinal flora.
METHODS
A prospective, randomized, controlled clinical study was designed to observe the efficacy and safety of SLF in the treatment of NAFLD. The study participants were randomly and evenly divided into control group and treatment group (SLF group). The control group made lifestyle adjustments, while the SLF group was treated with SLF on top of the control group. Both groups were participated in the study for 12 consecutive weeks. Furthermore, the feces of the two groups were collected before and after treatment. The intestinal flora of each group and healthy control (HC) were detected utilizing 16S rRNA gene sequencing.
RESULTS
Compared with the control group, the SLF group showed significant improvements in liver function, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), meanwhile, patients had significantly lower lipid and homeostasis model assessment of insulin resistance (HOMA-IR) with better security. Intestinal flora 16S rRNA gene sequencing results indicated reduced flora diversity and altered species abundance in patients with NAFLD. At the phylum level, levels were reduced. Although and did not differ significantly between HC and NAFLD, when grouped by alanine transaminase (ALT) and aspartate transaminase (AST) levels in NAFLD, levels were significantly higher in patients with ALT or AST abnormalities, while was significantly lower. Clinical correlation analysis showed that positively correlated with gender, age, ALT, AST, LSM, and Fibroscan-AST (FAST) score, while the opposite was true for . At the genus level, the levels of , , , , group , , , and were reduced, whereas abundance of increased. There was no statistically significant difference in and levels in the SLF group before and after treatment, but both bacteria tended to retrace. At the genus level, ( family), ( family), and ( family) were significantly higher in the SLF group after treatment, and there was also a tendency for ( family) to be back-regulated toward HC.
CONCLUSIONS
SLF can improve liver function and glucolipid metabolism in patients with NAFLD and lower down liver fat content to some extent. SLF could be carried out by regulating the disturbance of intestinal flora, especially , group, and genus.
Topics: Humans; Clostridiales; Gastrointestinal Microbiome; Non-alcoholic Fatty Liver Disease; RNA, Ribosomal, 16S; Spleen; Drugs, Chinese Herbal
PubMed: 36743913
DOI: 10.3389/fendo.2022.1107071 -
Nature Jul 2012The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative...
The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(−/−), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(−/−) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.
Topics: Animals; Bile Acids and Salts; Bilophila; Colitis; Diet, Fat-Restricted; Dietary Fats; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Metagenome; Mice; Mice, Inbred C57BL; Milk; Molecular Sequence Data; Safflower Oil; Sulfites; Taurine; Taurocholic Acid; Th1 Cells
PubMed: 22722865
DOI: 10.1038/nature11225 -
Dietary Plant and Animal Protein Sources Oppositely Modulate Fecal and in Vegetarians and Omnivores.Microbiology Spectrum Apr 2022The food we eat not only nourishes our bodies but also provides nutrients to the bacteria living in our guts. Gut bacterial communities are known to be affected by many...
The food we eat not only nourishes our bodies but also provides nutrients to the bacteria living in our guts. Gut bacterial communities are known to be affected by many factors, including diet and bowel cleansing, but the impacts of vegetarian and omnivore diets on fecal bacterial composition are still uncertain. In this study, we analyzed the bacterial compositions of fecal samples from vegetarians and omnivores 5 to 7 days after bowel cleansing, and we correlated specific dietary constituents with the relative abundances of specialized fecal bacteria. A total of 46 participants (23 vegetarians and 23 omnivores) were recruited. All participants underwent standard bowel cleansing before colonoscopy screening. Fecal samples were collected from each participant 5 to 7 days after bowel cleansing, and the fecal microbiota compositions were analyzed with next-generation sequencing. Sixteen participants also provided an image-based dietary record for nutritional assessment. No major differences between dietary groups were observed in terms of fecal bacterial richness, alpha diversity, or beta diversity. A minority of potential pathobionts tended to be elevated in omnivores compared to vegetarians, whereas potential probiotic species tended to be higher in the vegetarians. Detailed dietary assessments further revealed that the plant- and animal-derived proteins may oppositely modulate the relative abundances of pathobionts Bilophila and Lachnoclostridium. However, these results were not statistically significant after multiple-comparison correction. These results suggest that specialized probiotic and pathobiont microbiota constituents are sensitive to the plant- or animal-derived dietary components ingested by vegetarians and omnivores after bowel cleansing. Dietary pattern and food choice are associated with expansion of gut pathobionts and risk for metabolic and colonic disease. However, the effects of dietary interventions on intestinal microbiota remain unclear. After bowel cleansing, potential pathobionts and probiotic bacteria were increased in omnivores and vegetarians, respectively. The pathobionts Bilophila and Lachnoclostridium were oppositely modulated by dietary animal and plant protein. From a clinical perspective, fecal pathobionts that may indicate risk for metabolic and colonic disease can potentially be modulated with dietary interventions.
Topics: Animals; Bacteria; Bilophila; Clostridiales; Colonic Diseases; Diet; Feces; Humans; Vegetarians
PubMed: 35285706
DOI: 10.1128/spectrum.02047-21 -
European Journal of Nutrition Oct 2020This study investigated the effect of food additives, artificial sweeteners and domestic hygiene products on the gut microbiome and fibre fermentation capacity.
PURPOSE
This study investigated the effect of food additives, artificial sweeteners and domestic hygiene products on the gut microbiome and fibre fermentation capacity.
METHODS
Faecal samples from 13 healthy volunteers were fermented in batch cultures with food additives (maltodextrin, carboxymethyl cellulose, polysorbate-80, carrageenan-kappa, cinnamaldehyde, sodium benzoate, sodium sulphite, titanium dioxide), sweeteners (aspartame-based sweetener, sucralose, stevia) and domestic hygiene products (toothpaste and dishwashing detergent). Short-chain fatty acid production was measured with gas chromatography. Microbiome composition was characterised with 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR).
RESULTS
Acetic acid increased in the presence of maltodextrin and the aspartame-based sweetener and decreased with dishwashing detergent or sodium sulphite. Propionic acid increased with maltodextrin, aspartame-based sweetener, sodium sulphite and polysorbate-80 and butyrate decreased dramatically with cinnamaldehyde and dishwashing detergent. Branched-chain fatty acids decreased with maltodextrin, aspartame-based sweetener, cinnamaldehyde, sodium benzoate and dishwashing detergent. Microbiome Shannon α-diversity increased with stevia and decreased with dishwashing detergent and cinnamaldehyde. Sucralose, cinnamaldehyde, titanium dioxide, polysorbate-80 and dishwashing detergent shifted microbiome community structure; the effects were most profound with dishwashing detergent (R = 43.9%, p = 0.008) followed by cinnamaldehyde (R = 12.8%, p = 0.016). Addition of dishwashing detergent and cinnamaldehyde increased the abundance of operational taxonomic unit (OTUs) belonging to Escherichia/Shigella and Klebsiella and decreased members of Firmicutes, including OTUs of Faecalibacterium and Subdoligranulum. Addition of sucralose and carrageenan-kappa also increased the abundance of Escherichia/Shigella and sucralose, sodium sulphite and polysorbate-80 did likewise to Bilophila. Polysorbate-80 decreased the abundance of OTUs of Faecalibacterium and Subdoligranulum. Similar effects were observed with the concentration of major bacterial groups using qPCR. In addition, maltodextrin, aspartame-based sweetener and sodium benzoate promoted the growth of Bifidobacterium whereas sodium sulphite, carrageenan-kappa, polysorbate-80 and dishwashing detergent had an inhibitory effect.
CONCLUSIONS
This study improves understanding of how additives might affect the gut microbiota composition and its fibre metabolic activity with many possible implications for human health.
Topics: Female; Fermentation; Food Additives; Gastrointestinal Microbiome; Humans; Hygiene; Male; RNA, Ribosomal, 16S; Sweetening Agents; Young Adult
PubMed: 31853641
DOI: 10.1007/s00394-019-02161-8 -
Microorganisms Oct 2022The aim of our work is to summarize the current state of knowledge on gut microbiota differences in children and adolescents with psychiatric disorders. To find the... (Review)
Review
The aim of our work is to summarize the current state of knowledge on gut microbiota differences in children and adolescents with psychiatric disorders. To find the relevant articles, the PubMed, Web of Science, and Google Scholar databases were searched. Articles in English presenting original data and comparing the composition of gut microbiota in child psychiatric patients with gut microbiota in healthy children and adolescents were selected. Finally, we identified 55 articles eligible for our purpose. The majority of patients with autism spectrum disorders (ASD) were investigated. A smaller number of studies evaluating the gut microbiota in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), Rett syndrome, anorexia nervosa, depressive disorder (DD), and tic disorders were found. The main findings of this research are discussed in our review, focusing on the age-related gut microbiota specificity for psychiatric disorders and the differences between individual diagnosis. To conclude, the gut microbiota in children and adolescents with psychiatric disorders is evidently different from that in controls. The most pronounced differences are seen in children with ASD, less in ADHD. Moreover, the changes are not identical to those in adult psychiatric patients, as and Bilophila were increased in adults, and decreased in children with ASD, and and were more frequently represented in adults, but less frequently represented in children with depression. The available data suggest some genera have a different abundance in individual psychiatric disorders (e.g., , , and ), suggesting their importance for the gut-brain axis. Other bacterial genera might be more important for the pathophysiology of specific disorder in children and adolescents, as and for ASD, or for DD. Based on the research findings, we assume that gut microbiota corrections have the potential to improve clinical symptoms in psychiatric patients.
PubMed: 36296284
DOI: 10.3390/microorganisms10102009 -
BMC Microbiology Dec 2022Hashimoto's thyroiditis (HT) is an autoimmune disease. Recent studies have found that the gut microbiota may play an important role in inducing HT, but there are no...
BACKGROUND
Hashimoto's thyroiditis (HT) is an autoimmune disease. Recent studies have found that the gut microbiota may play an important role in inducing HT, but there are no systematic studies on the changes in the gut microbiota during the development of HT.
METHODS
In this study, 16S rDNA high-throughput sequencing technology in combination with the Kruskal-Wallis test, CCA/RDA analysis, Spearman correlation analysis, and other statistical methods were used to analyze the effects of age, gender, hormones, and other environmental factors on gut microbiota by comparing the differences in the microbiota at different stages of HT development.
RESULTS
The results showed that there were differences in the gut microbiota composition between healthy people (HCA) and in patients with HT. Lachnoclostridium, Bilophila, and Klebsiella were enriched in the HCA group, while Akkermansia, Lachnospiraceae, Bifidobacterium, Shuttleia, and Clostriworthdia were enriched in the HT group. Environmental factors analysis revealed that the Bifidobacterium and Klebsiella were two groups of bacteria that have undergone dramatic changes in HCA and HT, and mainly affected by gender. Romboutsia and Haemophilus regulated by the hormone of free triiodothyronine (FT3) may promote the development of HT, while Faecalibacterium and Lachnospiraceae regulated by free thyroxine (FT4) may protect the host.
CONCLUSIONS
Comprehensive studies have shown that gender is an important factor affecting gut microbial composition, but with the development of HT, hormones, age, and TSH begin to become dominant factors.
Topics: Humans; Gastrointestinal Microbiome; Hashimoto Disease; Hormones
PubMed: 36564707
DOI: 10.1186/s12866-022-02739-z -
Frontiers in Cellular and Infection... 2022Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial... (Review)
Review
Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3, Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of , , and and a decrease in genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including , , , and , suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Disease Models, Animal; Dysbiosis; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Mice; Microfilament Proteins; Nerve Tissue Proteins; Quality of Life
PubMed: 35846755
DOI: 10.3389/fcimb.2022.905841