-
Progress in Molecular Biology and... 2020Although there is associative evidence linking fecal microbiome profile to health and disease, many studies have not considered the confounding effects of dietary... (Review)
Review
Although there is associative evidence linking fecal microbiome profile to health and disease, many studies have not considered the confounding effects of dietary intake. Consuming food provides fermentable substrate which sustains the microbial ecosystem that resides with most abundance in the colon. Western, Mediterranean and vegetarian dietary patterns have a role in modulating the gut microbiota, as do trending restrictive diets such the paleolithic and ketogenic. Altering the amount or ratio of carbohydrate, protein and fat, particularly at the extremes of intake, impacts the microbiome. Diets high in fermentable carbohydrates support the relative abundance of Bifidobacterium, Prevotella, Ruminococcus, Dorea and Roseburia, among others, capable of degrading polysaccharides, oligosaccharides and sugars. Conversely, very high fat diets increase bile-resistant organisms such as Bilophila and Bacteroides. Food form, whole foods vs. ultra-processed, alters the provision of macronutrient substrate to the colon due to differing digestibility, and thereby may impact the microbiota and its metabolic activity. In addition, phytochemicals in plant-based foods have specific and possibly prebiotic effects on the microbiome. Further, food ingredients such as certain low-calorie sweeteners enhance Bifidobacterium spp. The weight of evidence to date suggests a high level of interindividual variability in the human microbiome vs. clearly defined, dietary-induced profiles. Healthful dietary patterns, emphasizing plant foods high in microbial-available carbohydrate, support favorable microbiome profiles active in saccharolytic fermentation. Future research into diet and microbiome should consider the balance of gut microbial-generated metabolites, an important link between microbiome profile and human health.
Topics: Diet; Humans; Microbiota; Nutrients
PubMed: 32475524
DOI: 10.1016/bs.pmbts.2020.04.006 -
Cell Host & Microbe Mar 2023The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune...
The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune surveillance remains poorly understood. Here, we analyzed the intratissue bacteria from CRC patient colon tissues. We found that the commensal bacteria belonging to the Lachnospiraceae family, including Ruminococcus gnavus (Rg), Blautia producta (Bp), and Dorea formicigenerans (Df), were enriched in normal tissues, while Fusobacterium nucleatum (Fn) and Peptostreptococcus anaerobius (Pa) were abundant in tumor tissues. Tissue-resident Rg and Bp reduced colon tumor growth and promoted the activation of CD8 T cells in immunocompetent mice. Mechanistically, intratissue Rg and Bp degraded lyso-glycerophospholipids that inhibited CD8 T cell activity and maintained the immune surveillance function of CD8 T cells. Lyso-glycerophospholipids alone promoted tumor growth that was abrogated with Rg and Bp injection. Collectively, intratissue Lachnospiraceae family bacteria facilitate the immune surveillance function of CD8 T cells and control colorectal cancer progression.
Topics: Animals; Mice; Colorectal Neoplasms; CD8-Positive T-Lymphocytes; Carcinogenesis; Colonic Neoplasms; Fusobacterium nucleatum
PubMed: 36893736
DOI: 10.1016/j.chom.2023.01.013 -
Annals of Neurology Jun 2021This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease.
OBJECTIVE
This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease.
METHODS
We sequenced the microbiota from healthy controls and relapsing-remitting MS (RRMS) and progressive MS patients and correlated the levels of bacteria with clinical features of disease, including Expanded Disability Status Scale (EDSS), quality of life, and brain magnetic resonance imaging lesions/atrophy. We colonized mice with MS-derived Akkermansia and induced experimental autoimmune encephalomyelitis (EAE).
RESULTS
Microbiota β-diversity differed between MS patients and controls but did not differ between RRMS and progressive MS or differ based on disease-modifying therapies. Disease status had the greatest effect on the microbiome β-diversity, followed by body mass index, race, and sex. In both progressive MS and RRMS, we found increased Clostridium bolteae, Ruthenibacterium lactatiformans, and Akkermansia and decreased Blautia wexlerae, Dorea formicigenerans, and Erysipelotrichaceae CCMM. Unique to progressive MS, we found elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased Blautia and Agathobaculum. Several Clostridium species were associated with higher EDSS and fatigue scores. Contrary to the view that elevated Akkermansia in MS has a detrimental role, we found that Akkermansia was linked to lower disability, suggesting a beneficial role. Consistent with this, we found that Akkermansia isolated from MS patients ameliorated EAE, which was linked to a reduction in RORγt+ and IL-17-producing γδ T cells.
INTERPRETATION
Whereas some microbiota alterations are shared in relapsing and progressive MS, we identified unique bacteria associated with progressive MS and clinical measures of disease. Furthermore, elevated Akkermansia in MS may be a compensatory beneficial response in the MS microbiome. ANN NEUROL 2021;89:1195-1211.
Topics: Adult; Akkermansia; Animals; Atrophy; Brain; Encephalomyelitis, Autoimmune, Experimental; Female; Gastrointestinal Microbiome; Humans; Male; Mice; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Quality of Life
PubMed: 33876477
DOI: 10.1002/ana.26084 -
Biomolecules Dec 2021Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors-genetic, metabolic, and dietary-intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to , , , , and , whereas , , , and spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and spp., while and are diminished. Children with NAFLD/NASH have a decreased proportion of spp. accompanied by an elevated proportion of , , , and spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.
Topics: Carcinoma, Hepatocellular; Child; Dysbiosis; Gastrointestinal Microbiome; Humans; Liver; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Prospective Studies; RNA, Ribosomal, 16S
PubMed: 35053205
DOI: 10.3390/biom12010056 -
International Journal of Molecular... Nov 2022There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological... (Review)
Review
There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.
Topics: Humans; Gastrointestinal Microbiome; Nervous System Diseases; Parkinson Disease; Microbiota; Akkermansia; Multiple Sclerosis; Prevotella; Clostridiaceae; Clostridiales; Stroke
PubMed: 36430144
DOI: 10.3390/ijms232213665 -
International Journal of Environmental... Mar 2023Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease mediated by autoimmune reactions against myelin proteins and gangliosides in the grey and... (Review)
Review
INTRODUCTION
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease mediated by autoimmune reactions against myelin proteins and gangliosides in the grey and white matter of the brain and spinal cord. It is considered one of the most common neurological diseases of non-traumatic origin in young people, especially in women. Recent studies point to a possible association between MS and gut microbiota. Intestinal dysbiosis has been observed, as well as an alteration of short-chain fatty acid-producing bacteria, although clinical data remain scarce and inconclusive.
OBJECTIVE
To conduct a systematic review on the relationship between gut microbiota and multiple sclerosis.
METHOD
The systematic review was conducted in the first quarter of 2022. The articles included were selected and compiled from different electronic databases: PubMed, Scopus, ScienceDirect, Proquest, Cochrane, and CINAHL. The keywords used in the search were: "multiple sclerosis", "gut microbiota", and "microbiome".
RESULTS
12 articles were selected for the systematic review. Among the studies that analysed alpha and beta diversity, only three found significant differences with respect to the control. In terms of taxonomy, the data are contradictory, but confirm an alteration of the microbiota marked by a decrease in Firmicutes, Lachnospiraceae, , , , , , , , and and an increase in Bacteroidetes, , , and . As for short-chain fatty acids, in general, a decrease in short-chain fatty acids, in particular butyrate, was observed.
CONCLUSIONS
Gut microbiota dysbiosis was found in multiple sclerosis patients compared to controls. Most of the altered bacteria are short-chain fatty acid (SCFA)-producing, which could explain the chronic inflammation that characterises this disease. Therefore, future studies should consider the characterisation and manipulation of the multiple sclerosis-associated microbiome as a focus of both diagnostic and therapeutic strategies.
Topics: Humans; Female; Adolescent; Dysbiosis; Neurodegenerative Diseases; Sclerosis; Microbiota; Fatty Acids, Volatile; Multiple Sclerosis; Bacteria
PubMed: 36901634
DOI: 10.3390/ijerph20054624 -
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2023Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that...
OBJECTIVE
Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune-related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK.
METHODS
To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes.
RESULTS
A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK.
CONCLUSION
This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome-metagenome interface in TAK subtype prediction and pathogenesis are suggested.
Topics: Humans; Takayasu Arteritis; Gastrointestinal Microbiome; Lipidomics; Inflammation; Metabolome; Behcet Syndrome; Cardiovascular Diseases
PubMed: 36054683
DOI: 10.1002/art.42331 -
Nutrients Dec 2021Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using... (Meta-Analysis)
Meta-Analysis
Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (-0.06, 95% CI -0.24, 0.12, = 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73, = 81%) and non-significantly lower Bacteroidetes (-4.79, 95% CI -10.77, 1.20, = 86%). At the genus level, lower relative proportions of and and higher , , , , , , , , , , , , and were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers.
Topics: Bacteria; Feces; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; Obesity
PubMed: 35010887
DOI: 10.3390/nu14010012 -
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 -
Hepatology (Baltimore, Md.) May 2023Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains...
BACKGROUND AND AIMS
Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression.
APPROACH AND RESULTS
Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12 , Allboaculum , and [ Ruminococcus ], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD + ) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype.
CONCLUSIONS
Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Mice, Inbred C57BL; Liver; Diet, High-Fat; Molecular Chaperones; Mitochondrial Proteins
PubMed: 35921199
DOI: 10.1002/hep.32705