scholarly journals Assessment of bidirectional relationships between 98 genera of the human gut microbiota and amyotrophic lateral sclerosis: a 2-sample Mendelian randomization study

BMC Neurology ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Gan Zhang ◽  
Tao Huang ◽  
Dongsheng Fan
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Human Gut ◽  
Standard Deviation Increase ◽  
Inverse Variance ◽  
Bidirectional Relationship ◽  
Weighted Median ◽  
Log Odds ◽  
Lateral Sclerosis

Abstract Background Growing evidence suggests a mutual interaction between gut microbiome alterations and ALS pathogenesis. However, previous studies were susceptible to potential confounding factors and reverse causation bias, likely leading to inconsistent and biased results. Objectives To decipher the potentially mutual relationship between gut microbiota and ALS, we used a bidirectional two-sample MR approach to examine the associations between the gut microbiome and ALS. Results Using the inverse variance-weighted method, OTU10032 unclassified Enterobacteriaceae species-level OTU and unclassified Acidaminococcaceae were associated with a higher risk of ALS (per relative abundance: OR, 1.04; 95% CI, 1.01–1.07; P = 0.011 and OR, 1.02; 95% CI, 1.01–1.04; P = 0.009, respectively). Importantly, Gamma-Glu-Phe was showed potential deleterious effects on the risk of ALS (genetically predicted per a 1-standard deviation increase in the level of Gamma-Glu-Phe: OR, 1.96; 95% CI, 1.50–2.55; P = 0.012). Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. Intriguingly, genetically predicted ALS was associated with an increase in the relative abundance of OTU4607_Sutterella (per 1-unit higher log odds: β, 2.23; 95% CI, 1.27–3.18; P = 0.020) and Lactobacillales_ORDER (per 1-unit higher log odds: β, 0.51; 95% CI, 0.09–0.94; P = 0.019). Conclusions Our findings provide novel evidence supporting the bidirectional relationship between the gut microbiota and ALS. These results may contribute to designing microbiome- and microbiome-dependent metabolite interventions in future ALS clinical trials.

scholarly journals Assessment of Bidirectional Relationships Between 98 Genera of the Human Gut Microbiota and Amyotrophic Lateral Sclerosis: A 2-Sample Mendelian Randomization Study

2021 ◽  
Author(s):  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Gan Zhang ◽  
Tao Huang ◽  
Dongsheng Fan
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Human Gut ◽  
Standard Deviation Increase ◽  
Inverse Variance ◽  
Bidirectional Relationship ◽  
Weighted Median ◽  
Log Odds ◽  
Lateral Sclerosis

Abstract BackgroundGrowing evidence suggests a mutual interaction between gut microbiome alterations and ALS pathogenesis. However, previous studies were susceptible to potential confounding factors and reverse causation bias, likely leading to inconsistent and biased results. Therefore, to decipher the potentially mutual relationship between gut microbiota and ALS, we used a bidirectional two-sample MR approach to examine the associations between the gut microbiome and ALS. Effects of potential metabolites on ALS were also estimated in MR design.ResultsUsing the inverse variance-weighted method, OTU10032 unclassified Enterobacteriaceae species-level OTU and unclassified Acidaminococcaceae were associated with a higher risk of ALS (per relative abundance: OR, 1.04; 95% CI, 1.01–1.07; P = 0.011 and OR, 1.02; 95% CI, 1.01–1.04; P = 0.009, respectively). Importantly, Gamma-Glu-Phe was showed potential deleterious effects on the risk of ALS (genetically predicted per a 1-standard deviation increase in the level of Gamma-Glu-Phe: OR, 1.96; 95% CI, 1.50–2.55; P = 0.012). Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. Intriguingly, genetically predicted ALS was associated with an increase in the relative abundance of OTU4607_Sutterella (per 1-unit higher log odds: β, 2.23; 95% CI, 1.27–3.18; P = 0.020) and Lactobacillales_ORDER (per 1-unit higher log odds: β, 0.51; 95% CI, 0.09–0.94; P = 0.019).ConclusionsOur findings provide novel evidence supporting the bidirectional relationship between the gut microbiota and ALS and highlight that a transsynaptic, glutaminergic, excitotoxic mechanism could provide a pathogenic basis for ALS. These results may contribute to designing microbiome- and microbiome-dependent metabolite interventions in future ALS clinical trials.

scholarly journals DETERMINING RELATIVE IMPORTANCE OF HUMAN GUT MICROBIOTA, AGE, GENDER AND LIFESTYLE PATTERN AS A PREDICTOR FOR BMI USING LOGMPIE DATA

2021 ◽  
Vol 21 (2) ◽  
Author(s):  
Komal Jani ◽  
Shelly Gupta
Keyword(s):  
Physical Activity ◽  
Body Mass Index ◽  
Random Forest ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Relative Importance ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Lifestyle Pattern

We use the ‘Relative Abundance Table’ and ‘LogMPIE Study Metadata’ from the “Landscape of Gut Microbiome - Pan-India Exploration”, or LogMPIE dataset to find out the relative importance of human gut microbiota abundance (specifically genus), age, gender, and lifestyle pattern as a predictor for BMI (Body Mass Index). The LogMPIE data is taken from 1004 subjects and 993 unique microorganisms are reported along with BMI, age, and physical activity. We use Random Forest Regressor to find out the relative importance of the above-mentioned features (microorganism genus abundance, age, gender, and lifestyle pattern) in predicting the BMI of a subject. The objective here is not the prediction of BMI using the features but to find out the relative importance of these features as much as these affect the BMI.

scholarly journals Effect of fructans, prebiotics and fibres on the human gut microbiome assessed by 16S rRNA-based approaches: a review

2020 ◽  
Vol 11 (2) ◽  
pp. 101-129 ◽  
Author(s):  
K.S. Swanson ◽  
W.M. de Vos ◽  
E.C. Martens ◽  
J.A. Gilbert ◽  
R.S. Menon ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Human Gut ◽  
Beta Glucan ◽  
Dietary Fibres ◽  
Sequencing Studies ◽  
Resistant Starches ◽  
The Impact

The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual’s microbiota to prebiotics and dietary fibres.

scholarly journals Gut Microbiome in a Russian Cohort of Pre- and Post-Cholecystectomy Female Patients

2021 ◽  
Vol 11 (4) ◽  
pp. 294
Author(s):  
Irina Grigor’eva ◽  
Tatiana Romanova ◽  
Natalia Naumova ◽  
Tatiana Alikina ◽  
Alexey Kuznetsov ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Gallstone Disease ◽  
Illumina Miseq ◽  
Rrna Gene ◽  
Bacterial Phyla ◽  
Female Patients ◽  
Composition And Structure ◽  
Before And After

The last decade saw extensive studies of the human gut microbiome and its relationship to specific diseases, including gallstone disease (GSD). The information about the gut microbiome in GSD-afflicted Russian patients is scarce, despite the increasing GSD incidence worldwide. Although the gut microbiota was described in some GSD cohorts, little is known regarding the gut microbiome before and after cholecystectomy (CCE). By using Illumina MiSeq sequencing of 16S rRNA gene amplicons, we inventoried the fecal bacteriobiome composition and structure in GSD-afflicted females, seeking to reveal associations with age, BMI and some blood biochemistry. Overall, 11 bacterial phyla were identified, containing 916 operational taxonomic units (OTUs). The fecal bacteriobiome was dominated by Firmicutes (66% relative abundance), followed by Bacteroidetes (19%), Actinobacteria (8%) and Proteobacteria (4%) phyla. Most (97%) of the OTUs were minor or rare species with ≤1% relative abundance. Prevotella and Enterocossus were linked to blood bilirubin. Some taxa had differential pre- and post-CCE abundance, despite the very short time (1–3 days) elapsed after CCE. The detailed description of the bacteriobiome in pre-CCE female patients suggests bacterial foci for further research to elucidate the gut microbiota and GSD relationship and has potentially important biological and medical implications regarding gut bacteria involvement in the increased GSD incidence rate in females.

scholarly journals Fruits and their impact on the gut microbiota, gut motility and constipation

2021 ◽  
Vol 12 (19) ◽  
pp. 8850-8866
Author(s):  
Zoi Katsirma ◽  
Eirini Dimidi ◽  
Ana Rodriguez-Mateos ◽  
Kevin Whelan
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Nutrient Content ◽  
Mechanisms Of Action ◽  
Human Gut ◽  
Gut Motility ◽  
Gut Function

A summary of the mechanisms of action by which fruit products confer effects on the human gut function, motility and the gut microbiome, as well as an exploration of the effects of processing on the active nutrient content and efficacy of fruits.

scholarly journals Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

2021 ◽  
Author(s):  
Yueqiong Ni ◽  
Zoltan Lohinai ◽  
Yoshitaro Heshiki ◽  
Balazs Dome ◽  
Judit Moldvay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Patients ◽  
Gut Microbiome ◽  
Human Gut ◽  
Microbial Composition ◽  
Shotgun Metagenomics ◽  
Lung Cancer Patients ◽  
Microbial Species ◽  
Functional Pathways

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

scholarly journals The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sarah L. Boddy ◽  
Ilaria Giovannelli ◽  
Matilde Sassani ◽  
Johnathan Cooper-Knock ◽  
Michael P. Snyder ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Phenotypic Variability ◽  
Personalised Medicine ◽  
Main Body ◽  
Body Of Knowledge ◽  
Environmental Component ◽  
Health And Disease ◽  
Lateral Sclerosis

Abstract Background Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. Main body The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. Conclusion Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.

scholarly journals Adopting seasonal regimen (Ritucharya) to modulate the seasonal variation in gut microbiome

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Deepthi. R ◽  
Vandana Rani M ◽  
Delvin T. Robin ◽  
Anusree Dileep
Keyword(s):  
Public Health ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Health Management ◽  
Disease Process ◽  
The Body ◽  
Leaky Gut ◽  
Human Gut ◽  
Extrinsic Factors ◽  
Application Prospects

AbstractThe science of Ayurveda with its strong and unique fundamentals holds its domain forever amidst all scientific and medical advancements. The concept of Shadkriyakala (the different phases of disease formation) holds relevance in preventive medicine and public health management as it provides ample chance to halt the disease process at each stage by timely intervention. In this review, we would like to bring to the limelight the relevance of Ritucharya (seasonal regimen) in primary prevention by modulating the gut microbiota. The modern gut microbiome researches now help us to better explore the Ayurveda theories of Agni (digestive fire) and Ama (metabolic toxins) preached centuries back. Ayurveda firmly proclaims that no disease ever arises without the derangement of Agni (digestive fire). The whole preventive and treatment methodology in Ayurveda focuses upon the modulation and management of “Agni” (digestive fire). When the functioning of Agni is deranged, Ama (metabolic toxin) is produced and it vitiates the doshas which spread throughout the body and manifest as varied diseases. A biomedical perspective of our reviews suggests that dysbiosis of microbial flora can cause a leaky gut by which the toxins of deranged digestive metabolism enter the bloodstream. Consequently, an inflammatory response occurs within the body which expresses out as diseases opportunistically. We meticulously reviewed the influence of extrinsic factors namely diet and climate on human gut microbiota, and our analysis emphasises the application prospects of Ritucharya (seasonal regimen), in regulating the dynamic host-microbe interaction.

scholarly journals Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Roessler ◽  
F Zimmermann ◽  
D Schmidt ◽  
U Escher ◽  
A Jasina ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Interindividual Variation ◽  
Funding Source ◽  
Microbial Composition ◽  
Atorvastatin Treatment ◽  
Qrt Pcr ◽  
16S Rna ◽  
Regulatory Properties

Abstract Background and aims The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome. Methods Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR. Results In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment. Conclusions Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation

scholarly journals ‘The way to a man's heart is through his gut microbiota’ – dietary pro- and prebiotics for the management of cardiovascular risk

2014 ◽  
Vol 73 (2) ◽  
pp. 172-185 ◽  
Author(s):  
Kieran M. Tuohy ◽  
Francesca Fava ◽  
Roberto Viola
Keyword(s):  
Metabolic Disease ◽  
Risk Factor ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Blood Cholesterol ◽  
Human Gut ◽  
Cvd Risk ◽  
Plant Foods ◽  
Whole Plant ◽  
The Way

The human gut microbiota has been identified as a possible novel CVD risk factor. This review aims to summarise recent insights connecting human gut microbiome activities with CVD and how such activities may be modulated by diet. Aberrant gut microbiota profiles have been associated with obesity, type 1 and type 2 diabetes and non-alcoholic fatty liver disease. Transfer of microbiota from obese animals induces metabolic disease and obesity in germ-free animals. Conversely, transfer of pathogen-free microbiota from lean healthy human donors to patients with metabolic disease can increase insulin sensitivity. Not only are aberrant microbiota profiles associated with metabolic disease, but the flux of metabolites derived from gut microbial metabolism of choline, phosphatidylcholine andl-carnitine has been shown to contribute directly to CVD pathology, providing one explanation for increased disease risk of eating too much red meat. Diet, especially high intake of fermentable fibres and plant polyphenols, appears to regulate microbial activities within the gut, supporting regulatory guidelines encouraging increased consumption of whole-plant foods (fruit, vegetables and whole-grain cereals), and providing the scientific rationale for the design of efficacious prebiotics. Similarly, recent human studies with carefully selected probiotic strains show that ingestion of viable microorganisms with the ability to hydrolyse bile salts can lower blood cholesterol, a recognised risk factor in CVD. Taken together such observations raise the intriguing possibility that gut microbiome modulation by whole-plant foods, probiotics and prebiotics may be at the base of healthy eating pyramids advised by regulatory agencies across the globe. In conclusion, dietary strategies which modulate the gut microbiota or their metabolic activities are emerging as efficacious tools for reducing CVD risk and indicate that indeed, the way to a healthy heart may be through a healthy gut microbiota.

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