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Nature Jan 2014Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and... (Clinical Trial)
Clinical Trial
Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
Topics: Adult; Bacteria; Bacteroides; Bile Acids and Salts; Bilophila; Carnivory; Diet; Diet, Vegetarian; Dietary Fats; Feces; Female; Fermentation; Food Microbiology; Gastrointestinal Tract; Gene Expression Regulation, Bacterial; Herbivory; Humans; Inflammatory Bowel Diseases; Male; Metagenome; Microbiota; Time Factors; Young Adult
PubMed: 24336217
DOI: 10.1038/nature12820 -
Frontiers in Immunology 2020is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the phylum, which are... (Review)
Review
is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the phylum, which are highly relevant in dysbiosis and disease. According to the taxonomy database at The National Center for Biotechnology Information, the genus consists of 13 species: , and and , and the subspecies subspecies vulgaris (vs. subsp.) are the newest strains featured outside that list. Although typically isolated from the human gut microbiome various species of this genus have been isolated from patients suffering from appendicitis, and abdominal and rectal abscess. It is possible that as spp. emerge, their identification in clinical samples may be underrepresented as novel MS-TOF methods may not be fully capable to discriminate distinct species as separate since it will require the upgrading of MS-TOF identification databases. In terms of pathogenicity, there is contrasting evidence indicating that may have protective effects against some diseases, including liver fibrosis, colitis, cancer immunotherapy, and cardiovascular disease. In contrast, other studies indicate is pathogenic in colorectal cancer and is associated with mental signs of depression. Gut dysbiosis seems to play a role in determining the compositional abundance of in the feces (., in non-alcoholic steatohepatitis, hepatic encephalopathy, and liver fibrosis). Since is a relatively recent sub-branch genus of the phylum, and since are commonly associated with chronic intestinal inflammation, this narrative review illustrates emerging immunological and mechanistic implications by which spp. correlate with human health.
Topics: Animals; Bacteroidetes; Dysbiosis; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Inflammation; Intestines; Mental Disorders; Mental Health; Neoplasms
PubMed: 32582143
DOI: 10.3389/fimmu.2020.00906 -
Biology Nov 2022The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety.... (Review)
Review
The possession of two X chromosomes may come with the risk of various illnesses, females are more likely to be affected by osteoarthritis, heart disease, and anxiety. Given the reported correlations between gut microbiome dysbiosis and various illnesses, the female gut microbiome is worthy of exploration. Herein, we discuss the composition of the female gut microbiota and its dysbiosis in pathologies affecting the female population. Using PubMed, we performed a literature search, using key terms, namely: "gut microbiome", "estrogen", "menopause", "polycystic ovarian syndrome", "pregnancy", and "menstruation". In polycystic ovarian syndrome (PCOS), the abundance of and the ratio of was found to be increased while that of ML615J-28 124-7 and S24-7 was reduced. In breast cancer, the abundance of was enhanced, while in cervical cancer, and were enhanced but and members of were decreased. In ovarian cancer, abundance was increased. Interestingly, the administration of , and ameliorated PCOS symptoms while that of a mix of W51, W23, W63, W52, W24, W37, W19, W56, and W58 alleviated vascular malfunction and arterial stiffness in obese postmenopausal women, and finally, while further research is needed, maybe protective against postmenopausal bone mass loss. As several studies report the therapeutic potential of probiotics and since the gut microbiota of certain female pathological states has been relatively characterized, we speculate that the administration of certain bacterial species as probiotics is warranted, as novel independent or adjunct therapies for various female pathologies.
PubMed: 36421397
DOI: 10.3390/biology11111683 -
Frontiers in Cellular and Infection... 2023The oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the...
INTRODUCTION
The oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the development of periodontitis. However, the specific role of certain gut microbiota taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality and potential confounding factors. Thus, we conducted a two-sample Mendelian Randomization study to comprehensively reveal the potential genetic causal effect of gut microbiota on periodontitis.
METHODS
SNPs strongly associated with 196 gut microbiota taxa (18,340 individuals) were selected as instrument variables, and periodontitis (17,353 periodontitis cases and 28,210 controls) was used as the outcome. The causal effect was analyzed via random effect inverse variance-weighted, weighted median, and MR-Egger. The sensitivity analyses were conducted using Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests.
RESULTS
Nine gut microbiota taxa ( 7, UCG-008, , , , , S24.7 group, , and ) are predicted to play a causal role in enhancing the risk of periodontitis (< 0.05). Besides, two gut microbiota taxa ( and 6) have potentially inhibitive causal effects on the risk of periodontitis (< 0.05). No significant estimation of heterogeneity or pleiotropy is detected.
CONCLUSION
Our study demonstrates the genetic causal effect of 196 gut microbiota taxa on periodontitis and provides guidance for the clinical intervention of periodontitis.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Periodontitis; Microbiota; Bacteroidetes; Clostridiales
PubMed: 37305424
DOI: 10.3389/fcimb.2023.1160993 -
Cancer Discovery Apr 2022Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show...
UNLABELLED
Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.
SIGNIFICANCE
The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti-PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873.
Topics: Animals; Bacteria; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Mice; Polyphenols
PubMed: 35031549
DOI: 10.1158/2159-8290.CD-21-0808 -
Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities.Scientific Reports Sep 2019The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and... (Randomized Controlled Trial)
Randomized Controlled Trial
The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders (Bacteroides, Parabacteroides, Blautia, Alistipes, Romboutsia and Roseburia). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia. A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia, Romboutsia, Ruminococcus2, Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides, Roseburia, Butyricicoccus, Alistipes, Parasutterella, Parabacteroides and Clostridium IV. Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.
Topics: Adult; Biomarkers; Body Mass Index; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Middle Aged; Obesity
PubMed: 31530820
DOI: 10.1038/s41598-019-49462-w -
Frontiers in Psychiatry 2019Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder...
Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. A PubMed literature search combined the terms "depression," "depressive disorder," "stool," "fecal," "gut," and "microbiome" to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Six eligible studies were found in which 50 taxa exhibited differences ( < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-, and -were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum , in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (, and ), six were lower (, and ), and six were divergent (, and ). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.
PubMed: 30804820
DOI: 10.3389/fpsyt.2019.00034 -
Nutrients Jun 2022The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but... (Review)
Review
The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but comparative literature is scarce. To fill this gap, we explored the contribution of the microbiota-gut-brain axis to the pathophysiology of seven brain-related diseases (attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, major depressive disorder, and bipolar disorder). In this article, we discussed changes in bacterial abundance and the metabolic implications of these changes on disease development and progression. Our central findings indicate that, mechanistically, all seven diseases are associated with a leaky gut, neuroinflammation, and over-activated microglial cells, to which gut-residing bacteria and their metabolites are important contributors. Patients show a pro-inflammatory shift in their colon microbiota, harbouring more Gram-negative bacteria containing immune-triggering lipopolysaccharides (LPS) in their cell walls. In addition, bacteria with pro-inflammatory properties (, , ) are found in higher abundances, whereas lower abundances of anti-inflammatory bacteria (, , , , , , , , ) are reported, when compared to healthy controls. On the metabolite level, aberrant levels of short-chain fatty acids (SCFAs) are involved in disease pathogenesis and are mostly found in lower quantities. Moreover, bacterial metabolites such as neurotransmitters (acetylcholine, dopamine, noradrenaline, GABA, glutamate, serotonin) or amino acids (phenylalanine, tryptophan) also play an important role. In the future, defined aberrations in the abundance of bacteria strains and altered bacterial metabolite levels could likely be possible markers for disease diagnostics and follow-ups. Moreover, they could help to identify novel treatment options, underlining the necessity for a deeper understanding of the microbiota-gut-brain axis.
Topics: Alzheimer Disease; Autism Spectrum Disorder; Bacteria; Brain; Depressive Disorder, Major; Dysbiosis; Humans
PubMed: 35807841
DOI: 10.3390/nu14132661 -
Nature Microbiology May 2022Intestinal proteases mediate digestion and immune signalling, while increased gut proteolytic activity disrupts the intestinal barrier and generates visceral...
Intestinal proteases mediate digestion and immune signalling, while increased gut proteolytic activity disrupts the intestinal barrier and generates visceral hypersensitivity, which is common in irritable bowel syndrome (IBS). However, the mechanisms controlling protease function are unclear. Here we show that members of the gut microbiota suppress intestinal proteolytic activity through production of unconjugated bilirubin. This occurs via microbial β-glucuronidase-mediated conversion of bilirubin conjugates. Metagenomic analysis of faecal samples from patients with post-infection IBS (n = 52) revealed an altered gut microbiota composition, in particular a reduction in Alistipes taxa, and high gut proteolytic activity driven by specific host serine proteases compared with controls. Germ-free mice showed 10-fold higher proteolytic activity compared with conventional mice. Colonization with microbiota samples from high proteolytic activity IBS patients failed to suppress proteolytic activity in germ-free mice, but suppression of proteolytic activity was achieved with colonization using microbiota from healthy donors. High proteolytic activity mice had higher intestinal permeability, a higher relative abundance of Bacteroides and a reduction in Alistipes taxa compared with low proteolytic activity mice. High proteolytic activity IBS patients had lower fecal β-glucuronidase activity and end-products of bilirubin deconjugation. Mice treated with unconjugated bilirubin and β-glucuronidase-overexpressing E. coli significantly reduced proteolytic activity, while inhibitors of microbial β-glucuronidases increased proteolytic activity. Together, these data define a disease-relevant mechanism of host-microbial interaction that maintains protease homoeostasis in the gut.
Topics: Animals; Bilirubin; Endopeptidases; Escherichia coli; Gastrointestinal Microbiome; Glucuronidase; Humans; Irritable Bowel Syndrome; Mice; Serine Proteases
PubMed: 35484230
DOI: 10.1038/s41564-022-01103-1 -
Microorganisms Aug 2023The role of the gut microbiota in modulating the risk of respiratory infections has garnered increasing attention. However, conventional clinical trials have faced...
The role of the gut microbiota in modulating the risk of respiratory infections has garnered increasing attention. However, conventional clinical trials have faced challenges in establishing the precise relationship between the two. In this study, we conducted a Mendelian randomization analysis with single nucleotide polymorphisms employed as instrumental variables to assess the causal links between the gut microbiota and respiratory infections. Two categories of bacteria, family and genus , were causally associated with the occurrence of upper respiratory tract infections (URTIs). Four categories of gut microbiota existed that were causally associated with lower respiratory tract infections (LRTIs), with order and genus showing a positive association and genus and genus showing a negative association. The metabolites and metabolic pathways only played a role in the development of LRTIs, with the metabolite deoxycholine acting negatively and menaquinol 8 biosynthesis acting positively. The identification of specific bacterial populations, metabolites, and pathways may provide new clues for mechanism research concerning therapeutic interventions for respiratory infections. Future research should focus on elucidating the potential mechanisms regulating the gut microbiota and developing effective strategies to reduce the incidence of respiratory infections. These findings have the potential to significantly improve global respiratory health.
PubMed: 37630668
DOI: 10.3390/microorganisms11082108