The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Askarova S
PROVIDER: S-EPMC7093326 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease.
Askarova Sholpan S Umbayev Bauyrzhan B Masoud Abdul-Razak AR Kaiyrlykyzy Aiym A Safarova Yuliya Y Tsoy Andrey A Olzhayev Farkhad F Kushugulova Almagul A
Frontiers in cellular and infection microbiology 20200318
Gut microbiome is a community of microorganisms in the gastrointestinal tract. These bacteria have a tremendous impact on the human physiology in healthy individuals and during an illness. Intestinal microbiome can influence one's health either directly by secreting biologically active substances such as vitamins, essential amino acids, lipids et cetera or indirectly by modulating metabolic processes and the immune system. In recent years considerable information has been accumulated on the rela ...[more]
Similar Datasets
Project description:Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
| S-EPMC5648830 | biostudies-other
Project description:A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide association study of gut microbiota genera from the MiBioGen consortium, we used polygenic risk score (PRS) analyses with the "best-fit" model implemented in PRSice-2 and determined the genetic correlation between 119 genera and AD in a discovery sample (ADc12 case/control: 1278/1293). To confirm the results from the discovery sample, we next repeated the PRS analysis in a replication sample (GenADA case/control: 799/778) and then performed a meta-analysis with the PRS results from both samples. Finally, we conducted a linear regression analysis to assess the correlation between the PRSs for the significant genera and the APOE genotypes. In the discovery sample, 20 gut microbiota genera were initially identified as genetically associated with AD case/control status. Of these 20, three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were independently significant in the replication sample. Meta-analysis with discovery and replication samples confirmed that ten genera had a significant correlation with AD, four of which were significantly associated with the APOE rs429358 risk allele in a direction consistent with their protective/risk designation in AD association. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was positively correlated with the APOE rs429358 risk allele in both samples. Overall, the host genetic factors influencing the abundance of ten genera are significantly associated with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.
| S-EPMC10066300 | biostudies-literature
Project description:The modern Paleolithic diet (MPD), featured by the consumption of vegetables, fruit, nuts, seeds, eggs, fish and lean meat, while excluding grains, dairy products, salt and refined sugar, has gained substantial public attention in recent years because of its potential multiple health benefits. However, to date little is known about the actual impact of this dietary pattern on the gut microbiome (GM) and its implications for human health. In the current scenario where Western diets, low in fiber while rich in industrialized and processed foods, are considered one of the leading causes of maladaptive GM changes along human evolution, likely contributing to the increasing incidence of chronic non-communicable diseases, we hypothesize that the MPD could modulate the Western GM towards a more "ancestral" configuration. In an attempt to shed light on this, here we profiled the GM structure of urban Italian subjects adhering to the MPD, and compared data with other urban Italians following a Mediterranean Diet (MD), as well as worldwide traditional hunter-gatherer populations from previous publications. Notwithstanding a strong geography effect on the GM structure, our results show an unexpectedly high degree of biodiversity in MPD subjects, which well approximates that of traditional populations. The GM of MPD individuals also shows some peculiarities, including a high relative abundance of bile-tolerant and fat-loving microorganisms. The consumption of plant-based foods-albeit with the exclusion of grains and pulses-along with the minimization of the intake of processed foods, both hallmarks of the MPD, could therefore contribute to partially rewild the GM but caution should be taken in adhering to this dietary pattern in the long term.
| S-EPMC6687155 | biostudies-literature
Project description:Fatty liver disease is the most common liver disease in the world. Its connection with the gut microbiome has been known for at least 80 y, but this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample of 6,269 Finnish participants. We based our models on biometric covariates and gut microbiome compositions from shallow metagenome sequencing. Our classification models could discriminate between individuals with a high FLI (≥60, indicates likely liver steatosis) and low FLI (<60) in internal cross-region validation, consisting of 30% of the data not used in model training, with an average AUC of 0.75 and AUPRC of 0.56 (baseline at 0.30). In addition to age and sex, our models included differences in 11 microbial groups from class Clostridia, mostly belonging to orders Lachnospirales and Oscillospirales. Our models were also predictive of the high FLI group in a different Finnish cohort, consisting of 258 participants, with an average AUC of 0.77 and AUPRC of 0.51 (baseline at 0.21). Pathway analysis of representative genomes of the positively FLI-associated taxa in (NCBI) Clostridium subclusters IV and XIVa indicated the presence of, e.g., ethanol fermentation pathways. These results support several findings from smaller case-control studies, such as the role of endogenous ethanol producers in the development of the fatty liver.
| S-EPMC7928040 | biostudies-literature
Project description:BackgroundAlthough some human studies have reported gut microbiome changes in individuals with Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI), gut microbiome alterations in preclinical AD, i.e., cerebral amyloidosis without cognitive impairment, is largely unknown.ObjectiveWe aimed to identify gut microbial alterations associated with preclinical AD by comparing cognitively normal (CN) older adults with cerebral Aβ deposition (Aβ+ CN) and those without cerebral Aβ deposition (Aβ- CN).MethodsSeventy-eight CN older participants (18 Aβ+ CN and 60 Aβ- CN) were included, and all participants underwent clinical assessment and Pittsburg compound B-positron emission tomography. The V3-V4 region of the 16S rRNA gene of genomic DNA extracted from feces was amplified and sequenced to establish the microbial community.ResultsGeneralized linear model analysis revealed that the genera Megamonas (B = 3.399, q<0.001), Serratia (B = 3.044, q = 0.005), Leptotrichia (B = 5.862, q = 0.024) and Clostridium (family Clostridiaceae) (B = 0.788, q = 0.034) were more abundant in the Aβ+ CN group than the Aβ- CN group. In contrast, genera CF231 (B = -3.237, q< 0.001), Victivallis (B = -3.447, q = 0.004) Enterococcus (B = -2.044, q = 0.042), Mitsuokella (B = -2.119, q = 0.042) and Clostridium (family Erysipelotrichaceae) (B = -2.222, q = 0.043) were decreased in Aβ+ CN compared to Aβ- CN. Notably, the classification model including the differently abundant genera could effectively distinguish Aβ+ CN from Aβ- CN (AUC = 0.823).ConclusionOur findings suggest that specific alterations of gut bacterial taxa are related to preclinical AD, which means these changes may precede cognitive decline. Therefore, examining changes in the microbiome may be helpful in preclinical AD screening.
| S-EPMC9707757 | biostudies-literature
Project description:The advent of high-throughput 'omics' technologies has improved our knowledge of gut microbiome in human health and disease, including Alzheimer's disease (AD), a neurodegenerative disorder. Frequent bidirectional communications and mutual regulation exist between the gastrointestinal tract and the central nervous system through the gut-brain axis. A large body of research has reported a close association between the gut microbiota and AD development, and restoring a healthy gut microbiota may curb or even improve AD symptoms and progression. Thus, modulation of the gut microbiota has become a novel paradigm for clinical management of AD, and emerging effort has focused on developing potential novel strategies for preventing and/or treating the disease. In this review, we provide an overview of the connection and causal relationship between gut dysbiosis and AD, the mechanisms of gut microbiota in driving AD progression, and the successes and challenges of implementing available gut microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation) in preventive and/or therapeutic preclinical and clinical intervention studies of AD. Finally, we discuss the future directions in this field.
| S-EPMC10631445 | biostudies-literature
Project description:BackgroundRapidly spreading parasitic infections like amoebic gill disease (AGD) are increasingly problematic for Atlantic salmon reared in aquaculture facilities and potentially pose a risk to wild fish species in surrounding waters. Currently, it is not known whether susceptibility to AGD differs between wild and farmed salmon. Wild Atlantic salmon populations are declining and this emerging disease could represent an additional threat to their long-term viability. A better understanding of how AGD affects fish health is therefore relevant for the accurate assessment of the associated risk, both to farming and to the well-being of wild populations. In this study, we assessed the impact of natural exposure to AGD on wild, hybrid and farmed post-smolt Atlantic salmon reared in a sea farm together under common garden conditions.ResultsWild fish showed substantially higher mortality levels (64%) than farmed fish (25%), with intermediate levels for hybrid fish (39%) suggesting that AGD susceptibility has an additive genetic basis. Metabolic rate measures representing physiological performance were similar among the genetic groups but were significantly lower in AGD-symptomatic fish than healthy fish. Gut microbial diversity was significantly lower in infected fish. We observed major shifts in gut microbial community composition in response to AGD infections. In symptomatic fish the relative abundance of key taxa Aliivibrio, Marinomonas and Pseudoalteromonas declined, whereas the abundance of Polaribacter and Vibrio increased compared to healthy fish.ConclusionsOur results highlight the stress AGD imposes on fish physiology and suggest that low metabolic-rate fish phenotypes may be associated with better infection outcomes. We consider the role increased AGD outbreak events and a warmer future may have in driving secondary bacterial infections and in reducing performance in farmed and wild fish.
| S-EPMC9479442 | biostudies-literature
Project description:Gut-microbiome-inflammation interactions have been linked to neurodegeneration in Alzheimer's disease (AD) and other disorders. We hypothesized that treatment with rifaximin, a minimally absorbed gut-specific antibiotic, may modify the neurodegenerative process by changing gut flora and reducing neurotoxic microbial drivers of inflammation. In a pilot, open-label trial, we treated 10 subjects with mild to moderate probable AD dementia (Mini-Mental Status Examination (MMSE) = 17 ± 3) with rifaximin for 3 months. Treatment was associated with a significant reduction in serum neurofilament-light levels (P < .004) and a significant increase in fecal phylum Firmicutes microbiota. Serum phosphorylated tau (pTau)181 and glial fibrillary acidic protein (GFAP) levels were reduced (effect sizes of -0.41 and -0.48, respectively) but did not reach statistical significance. In addition, there was a nonsignificant downward trend in serum cytokine interleukin (IL)-6 and IL-13 levels. Cognition was unchanged. Increases in stool Erysipelatoclostridium were correlated significantly with reductions in serum pTau181 and serum GFAP. Insights from this pilot trial are being used to design a larger placebo-controlled clinical trial to determine if specific microbial flora/products underlie neurodegeneration, and whether rifaximin is clinically efficacious as a therapeutic.
| S-EPMC8804600 | biostudies-literature
Project description:Despite the increasing evidence of links between human gut and health, the number of gut microbiomes that have been studied to date at a country level are surprisingly low. Mediterranean countries, including some of the most long-lived and healthy countries in the world, have not been considered so far in those studies at a large scale. The main objective of this work is to characterize the gut microbiome of a healthy adult population of a Mediterranean, paradigmatically healthy country: Spain. Stool samples from 530 healthy volunteers were collected, total metagenomic DNA extracted, and the microbial profiles determined through 16S rRNA metataxonomic sequencing. Our results confirm the associations between several microbial markers and different variables, including sex, age, BMI and diet choices, and bring new insights into the relationship between microbiome and diet in the Spanish population. Remarkably, some of the associations found, such as the decrease of Faecalibacterium with age or the link of Flavonifractor with less healthy dietary habits, have been barely noticed in other large-scale cohorts. On the other hand, a range of links between microorganisms, diet, and lifestyle coincide with those reported in other populations, thus increasing the robustness of such associations and confirming the importance of these microbial markers across different countries. Overall, this study describes the Spanish “normal” microbiome, providing a solid baseline for future studies investigating the effects of gut microbiome composition and deviations in the adherence to the Mediterranean diet.
| S-EPMC8580991 | biostudies-literature
Project description:The root cause of non-inherited Alzheimer's disease (AD) remains unknown despite hundreds of research studies performed to attempt to solve this problem. Since proper prophylaxis remains the best strategy, many scientists have studied the risk factors that may affect AD development. There is robust evidence supporting the hypothesis that cardiovascular diseases (CVD) may contribute to AD progression, as the diseases often coexist. Therefore, a lack of well-defined diagnostic criteria makes studying the relationship between AD and CVD complicated. Additionally, inflammation accompanies the pathogenesis of AD and CVD, and is not only a consequence but also implicated as a significant contributor to the course of the diseases. Of note, АроЕε4 is found to be one of the major risk factors affecting both the cardiovascular and nervous systems. According to genome wide association and epidemiological studies, numerous common risk factors have been associated with the development of AD-related pathology. Furthermore, the risk of developing AD and CVDs appears to be increased by a wide range of conditions and lifestyle factors: hypertension, dyslipidemia, hypercholesterolemia, hyperhomocysteinemia, gut/oral microbiota, physical activity, and diet. This review summarizes the literature and provides possible mechanistic links between CVDs and AD.
| S-EPMC8033981 | biostudies-literature