Microbiome-based Interventions Research Articles

Effects of microbiome-based interventions on neurodegenerative diseases: a systematic review and meta-analysis

Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, − 0.57; 95% CI − 0.93 to − 0.21; I2 = 42%; P = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.

Investigating the Roles of Gut Microbiome in the Progression of Neurodegenerative Diseases: Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS)

Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS), pose global health burdens due to their incurable and degenerative nature. Emerging evidence highlights the complex interplay between the gut microbiome and the central nervous system (CNS), revealing novel mechanisms of ND pathogenesis and progression. This review integrates current literature, correlation analyses, and inferential statistics to elucidate the impact of gut microbiome dysbiosis on NDs and identify potential diagnostic biomarkers and therapeutic targets. The gut-brain axis (GBA), a bidirectional communication network between the gut and the brain, modulates neurological function and disease outcomes. Correlation analyses demonstrated significant associations between gut microbiome perturbations and ND parameters, implying a causal role for gut dysbiosis in ND pathogenesis. Inferential statistics revealed distinct microbial profiles between ND cohorts and healthy controls, indicating a shared gut dysbiosis across diverse NDs. Studies investigating microbial taxa, metabolites, and signaling pathways have provided insights into the molecular mechanisms underlying gut microbiome-mediated effects on neurodegeneration. Elucidating the reciprocal interactions between the gut microbiome and the host physiology is essential for deciphering the GBA’s role in NDs. Despite advances, knowledge gaps remain. Longitudinal studies are required to monitor gut microbiome dynamics over ND progression. Mechanistic studies are needed to establish how gut microbiome composition affects disease. Methodological standardization for gut microbiome assessment is imperative for rigorous research. Future endeavors should aim to translate findings into clinical applications to exploit microbiome-based interventions for enhanced neurological outcomes in NDs.

Abstract CT258: Phase II trial of fecal microbiota transplantation in combination with ipilimumab and nivolumab in patients with advanced cutaneous melanoma (FMT-LUMINate trial)

Abstract Background: Several trials combining microbiome-based interventions with immune checkpoints inhibitors (ICI) are currently underway. Previous studies showed the potential of fecal microbiota transplant (FMT) to circumvent secondary anti-PD-1 resistance or improve first-line anti-PD-1 response in patients with advanced melanoma. Whether FMT can be used safely in combination with anti-PD-1/anti-CTLA-4 (dual ICI) and its impact on the microbiome composition remain unknown. Here, we report results from combining FMT with dual ICI in previously untreated patients (pts) with advanced melanoma (NCT04951583). Methods: 20 pts with previously untreated advanced melanoma were included. FMT from healthy donors was administered in oral capsules after bowel preparation 1 week prior to start of dual ICI. A total of 6 different donors were used. The primary endpoint was safety. Secondary endpoints included objective response rate (ORR) and microbiome shift using shotgun metagenomic sequencing. Longitudinal serum Il1rl1 gene product (sST2) epithelial integrity marker was measured. Stool from pts before and after FMT were transplanted into avatar mice (MCA-205 or B16 OVA) and then treated with dual ICI. Results: In the 20 pts enrolled, 13 (65%) were male and median age was 56. Median follow-up was 6 months (range (IQR) 3.23; 12.33). FMT alone resulted in grade 1 toxicities. Grade 1-2 immune related adverse event (irAE) occurred in 80% of pts and 65% developed grade >3 irAE. Diarrhea or colitis was the most frequent grade 3 irAE occurring in 4 (20%). 2 pts developed myocarditis (grade 3 and grade 4, respectively). 6 (30%) pts completed all 4 cycles of dual ICI. 6 (43%) pts that developed irAE grade 3 received FMT from the same donor. ORR was 70% (2 complete responses (CR) and 12 partial responses (PR)). Two pts died; one from unknown cause in PR and one from disease progression. Microbiome profiling beta-diversity analyses revealed separate clustering of responders (R) and non-responders (NR) post-FMT (p=0.024). We observed an enrichment of Prevotella copri, Ruminoccocaceae and Eubacterium in R pts post-FMT. Pts who developed colitis were found to have a higher level of sST2 in plasma 1 week after FMT in comparison to those who did not develop colitis (p<0.05). In both avatar murine tumor models, microbiome composition with R pts’ feces (without ICI) 1 month post-FMT had reduced tumor growth compared to those treated with respective NR pt feces. Additionally, dual ICI led to significantly improved tumor control in mice treated with R pts’ feces post-FMT(p<0.005). Conclusions: The addition of FMT to dual ICI resulted in significant irAEs that occurred earlier, although the proportion was similar to previously described literature, with encouraging ORR. Metagenomic analysis depicted differences in the microbiome profiles of R compared to NR pts post FMT. These results support the study of FMT and immunotherapy in the randomized setting. Citation Format: Sreya Duttagupta, Meriem Messaoudene, Rahima Jamal, Catalin Mihalcioiu, Karl Belanger, John Lenehan, Wiam Belkaid, Seema Nair Parvathy, Jade Maillou, Yongjia Hu, Mayra Ponce, Taiki Hakozaki, Eder Mendez Salazar, Michael Silverman, Saman Maleki Vareki, Arielle Elkrief, Bertrand Routy. Phase II trial of fecal microbiota transplantation in combination with ipilimumab and nivolumab in patients with advanced cutaneous melanoma (FMT-LUMINate trial) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT258.

Workplace food purchases, dietary intake, and gut microbial metabolites in a secondary analysis of the ChooseWell 365 study

BackgroundDietary choices can affect human health through alterations in gut microbial metabolism, and gut microbial metabolites could serve as biomarkers for disease risk conferred by dietary intake. However, self-reported dietary intake may not reflect true intake. ObjectivesWe identified circulating metabolites, including gut microbiome-related metabolites, associated with adherence to a healthy diet in the ChooseWell 365 study. In this randomized clinical trial, the dietary choices of hospital employees were assessed over 24 mo using not only 24-h dietary recalls but also electronic records of hospital cafeteria purchases. MethodsPlasma metabolites were profiled from 470 participants. Two targeted metabolomics methods were developed and implemented to expand detection coverage for metabolites related to gut microbial activity. Linear regression models were used to associate metabolites with Healthy Purchasing Scores (HPSs) derived from cafeteria purchases and Healthy Eating Index-2015 (HEI-15) scores derived from dietary recalls. ResultsFourteen metabolites were concordantly associated with the HPS and HEI-15 scores in multivariable models adjusted for age, gender, and race, including the gut microbiome-related metabolites indole-3-propionic acid (HPS, β: 0.16, 95% CI: 0.07, 0.26, P = 7.32 × 10−4; HEI-15, β: 0.16, 95% CI: 0.07, 0.25, P = 6.79 × 10−4), hippuric acid (HPS, β: 0.11, 95% CI: 0.02, 0.21, P = 1.97 × 10−2; HEI-15, β: 0.10, 95% CI: 0.01, 0.19, P = 3.14 × 10−2), and indoxyl sulfate (HPS, β = −0.13, 95% CI: −0.23, −0.03, P = 8.21 × 10−3; HEI-15, β: −0.12, 95% CI: −0.22, −0.03, P = 8.50 × 10−3). These gut microbial metabolites were associated with the intake of specific food groups, such as whole fruits. These metabolites were also associated with clinical variables, including blood pressure, diabetes or prediabetes, and body mass index. ConclusionsIn a secondary analysis of the ChooseWell 365 study, associations between circulating gut microbiome–related metabolites and a healthy diet were confirmed using both objective and subjective measures of consumption. Accurate identification of diet-associated metabolites may help guide dietary or microbiome-based interventions aimed at disease prevention.

Predispose, precipitate, perpetuate, and protect: how diet and the gut influence mental health in emerging adulthood.

Medicine often employs the 4Ps of predisposing, precipitating, perpetuating, and protective factors to identify salient influences on illness states, and to help guide patient care. Mental illness is a significant cause of morbidity and mortality worldwide. Mental health is a complex combination of biological, psychological, environmental, and social factors. There is growing interest in the gut-brain-microbiome (GBM) axis and its impact on mental health. We use the medical model of the 4Ps to explore factors involving the connection between nutrition and the GBM axis and their associated risks with mental health problems in emerging adults (EAs), a life stage when mental illness onset is the most common. We review the impact of current dietary trends on the GBM and on mental health, and the role that gut microbiome-based interventions can have in modulating the GBM axis of EAs. We discuss the implications of gut health on the GBM and areas for clinical intervention.

The coral microbiome in sickness, in health and in a changing world.

Stony corals, the engines and engineers of reef ecosystems, face unprecedented threats from anthropogenic environmental change. Corals are holobionts that comprise the cnidarian animal host and a diverse community of bacteria, archaea, viruses and eukaryotic microorganisms. Recent research shows that the bacterial microbiome has a pivotal role in coral biology. A healthy bacterial assemblage contributes to nutrient cycling and stress resilience, but pollution, overfishing and climate change can break down these symbiotic relationships, which results in disease, bleaching and, ultimately, coral death. Although progress has been made in characterizing the spatial-temporal diversity of bacteria, we are only beginning to appreciate their functional contribution. In this Review, we summarize the ecological and metabolic interactions between bacteria and other holobiont members, highlight the biotic and abiotic factors influencing the structure of bacterial communities and discuss the impact of climate change on these communities and their coral hosts. We emphasize how microbiome-based interventions can help to decipher key mechanisms underpinning coral health and promote reef resilience. Finally, we explore how recent technological developments may be harnessed to address some of the most pressing challenges in coral microbiology, providing a road map for future research in this field.

Unveiling the Gastrointestinal Microbiome Symphony: Insights Into Post-Gastric Cancer Treatment Microbial Patterns and Potential Therapeutic Avenues.

This review delved into the intricate relationship between the gastrointestinal microbiome and gastric cancer, particularly focusing on post-treatment alterations, notably following gastrectomy, and the effects of anticancer therapies. Following gastrectomy, analysis of fecal samples revealed an increased presence of oral cavity aerotolerant and bile acid-transforming bacteria in the intestine. Similar changes were observed in the gastric microbiome, highlighting significant alterations in taxon abundance and emphasizing the reciprocal interaction between the oral and gastric microbiomes. In contrast, the impact of chemotherapy and immunotherapy on the gut microbiome was subtle, although discernible differences were noted between treatment responders and non-responders. Certain bacterial taxa showed promise as potential prognostic markers. Notably, probiotics emerged as a promising approach for postgastrectomy recovery, displaying the capacity to alleviate inflammation, bolster immune responses, and maintain a healthy gut microbiome. Several strains, including Bifidobacterium, Lactobacillus, and Clostridium butyricum, exhibited favorable outcomes in postoperative patients, suggesting their potential roles in comprehensive patient care. In conclusion, understanding the intricate interplay between the gastrointestinal microbiome and gastric cancer treatment offers prospects for predicting responses and enhancing postoperative recovery. Probiotics, with their positive impact on inflammation and immunity, have emerged as potential adjuncts in patient care. Continued research is imperative to fully harness the potential of microbiome-based interventions in the management of gastric cancer.

Microbiome in Female Reproductive Health: Implications for Fertility and Assisted Reproductive Technologies

Abstract The microbiome plays a critical role in the process of conception and the outcomes of pregnancy. Disruptions in microbiome homeostasis in women of reproductive age can lead to various pregnancy complications, which significantly impact maternal and fetal health. Recent studies have associated the microbiome in the female reproductive tract (FRT) with assisted reproductive technology (ART) outcomes, and restoring microbiome balance has been shown to improve fertility in infertile couples. This review provides an overview of the role of the microbiome in female reproductive health, including its implications for pregnancy outcomes and ARTs. Additionally, recent advances in the use of microbial biomarkers as indicators of pregnancy disorders are summarized. A comprehensive understanding of the characteristics of the microbiome before and during pregnancy and its impact on reproductive health will greatly promote maternal and fetal health. Such knowledge can also contribute to the development of ARTs and microbiome-based interventions.

Exploring the impact of gut microbiota on abdominal aortic aneurysm risk through a bidirectional Mendelian randomization analysis

ObjectiveThe abdominal aortic aneurysm (AAA) is associated with alterations in the composition of the gut microbiota; however, the precise causal relationship remains unclear. Elucidating this complex interplay could provide new insights into the pathogenesis of AAA. MethodsA bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide association study summary data on the gut microbiota (n = 18,340) and AAA (n = 353,087). A total of 196 gut microbial taxa across taxonomic levels were examined for their potential causal effects on AAA risk. Conversely, the effect of AAA on these microbial taxa was also analyzed. ResultsNine microbial taxa were identified as having a causal influence on AAA risk. Specifically, increased risk were associated with genus Bilophila (odds ratio [OR], 1.359; P = .0119), genus Catenibacterium (OR, 1.348; P = .0058), genus family XIII AD3011 group (OR, 1.507; P = .004), genus Oxalobacter (OR, 1.157; P = .0449), and genus Prevotella 7 (OR, 1.194; P = .0306), whereas decreased risks were linked to class Lentisphaeria (OR, 0.829; P = .0361), order Victivallales (OR, 0.829; P = .0361), family Victivallaceae (OR, 0.814; P = .0057), and genus Anaerotruncus (OR, 0.773; P = .0497). Furthermore, AAA was found to influence the abundance of 14 microbial taxa across various taxonomic levels. Notably, bidirectional associations were observed with the class Lentisphaeria and the order Victivallales. ConclusionsThis study provides novel evidence for a reciprocal causal relationship between gut microbiota and AAA risk, thereby offering new insights into the pathogenesis of AAA. These findings also suggest promising avenues for microbiome-based therapeutic interventions.

Role of the Human Microbiome in Health and Disease in United Kingdom

Purpose: The aim of the study was to investigate the role of the human microbiome in health and disease in United Kingdom.
 Methodology: The study adopted a desktop methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library
 Findings: The microbiome influences human health and disease by providing essential functions, such as nutrient metabolism, immune regulation, and protection against pathogens. However, the microbiome can also be disrupted by various factors, such as diet, lifestyle, age, genetics, and infections, leading to dysbiosis and increased risk of diseases. In the United Kingdom, research on the microbiome has been conducted to understand its role in various conditions, such as obesity, diabetes, inflammatory bowel disease, cancer, and mental health. The findings suggest that modulating the microbiome through dietary interventions, probiotics, prebiotics, or fecal microbiota transplantation may offer novel strategies for preventing or treating these diseases.
 Unique Contribution to Theory, Practice and Policy: Microbiome Dysbiosis Theory, Hygiene Hypothesis Theory and Microbiota-Brain-Gut Axis Theory may be used to anchor future studies on role of the human microbiome in health and disease in United Kingdom. Findings can invest in the development of microbiome-based therapeutics, including fecal microbiota transplantation (FMT), engineered probiotics, and microbial-derived products. Policymakers should establish a regulatory framework for microbiome-based interventions, ensuring their safety, efficacy, and accessibility.

Environmental enrichment in combination with Bifidobacterium breve HNXY26M4 intervention amplifies neuroprotective benefits in a mouse model of Alzheimer’s disease by modulating glutamine metabolism of the gut microbiome

The gut microbiota-brain axis has emerged as a novel target for Alzheimer’s disease (AD), a neurodegenerative disease characterised by behavioural and cognitive impairment. However, most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements. Here, we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment (EE) training. In this study, we found that compared with EE or B. breve treatment alone, B. breve intervention combined with EE amplified its neuroprotective effects on AD mice, as reflected by improved cognition, inhibited neuroinflammation and enhanced synaptic function. Moreover, using microbiome and metabolome profiling, we found that the combination of B. breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes. Finally, by integrating behavioural and neurological data with metabolomic profiles, we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut–brain interactions. Collectively, combined B. breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome. Our findings provide a promising multidomain intervention strategy, with a combination of dietary microbiome-based and lifestyle-targeted interventions, to promote brain function and delay the progression of AD.

The intersection of social determinants of health, the microbiome, and health outcomes in immigrants: A scoping review.

In the present scoping review, we explore whether existing evidence supports the premise that social determinants of health (SDoH) affect immigrant health outcomes through their effects on the microbiome. We adapt the National Institute on Minority Health and Health Disparities' research framework to propose a conceptual model that considers the intersection of SDoH, the microbiome, and health outcomes in immigrants. We use this conceptual model as a lens through which to explore recent research about SDoH, biological factors associated with changes to immigrants' microbiomes, and long-term health outcomes. In the 17 articles reviewed, dietary acculturation, physical activity, ethnicity, birthplace, age at migration and length of time in the host country, socioeconomic status, and social/linguistic acculturation were important determinants of postmigration microbiome-related transformations. These factors are associated with progressive shifts in microbiome profile with time in host country, increasing the risks for cardiometabolic, mental, immune, and inflammatory disorders and antibiotic resistance. The evidence thus supports the premise that SDoH influence immigrants' health postmigration, at least in part, through their effects on the microbiome. Omission of important postmigration social-ecological variables (e.g., stress, racism, social/family relationships, and environment), limited research among minoritized subgroups of immigrants, complexity and inter- and intra-individual differences in the microbiome, and limited interdisciplinary and biosocial collaboration restrict our understanding of this area of study. To identify potential microbiome-based interventions and promote immigrants' well-being, more research is necessary to understand the intersections of immigrant health with factors from the biological, behavioral/psychosocial, physical/built environment, and sociocultural environment domains at all social-ecological levels.

Gut microbiome relationship with arrhythmias and conduction blocks: A two-sample Mendelian randomization study.

Past research based on observations has suggested that the gut microbiome (GM) could play a role in developing arrhythmias and conduction blocks. Nonetheless, the nature of this association remains uncertain due to the potential for reverse causation and confounding factors in observational research. The aim of this investigation is to elucidate the causal relationship between GM and the development of arrhythmias as well as conduction blocks. This study collected summary statistics regarding GM, arrhythmias, and conduction blocks. Two-sample Mendelian randomization (MR) analysis was carried out employing various methods, with inverse variance weighted being the primary approach, followed by weighted median, simple mode, MR-Egger, and MR-PRESSO. Moreover, the MR findings were corroborated through multiple sensitivity analyses. Among them, for atrial fibrillation and flutter (AF), phylum_Actinobacteria and genus_RuminococcaceaeUCG004 demonstrated a negative correlation, while order_Pasteurellales, family_Pasteurellaceae, and genus_Turicibacter were associated with an increased risk. In the case of paroxysmal tachycardia (PT), genus_Holdemania and genus_Roseburia were found to reduce risk. For atrioventricular block (AVB), order_Bifidobacteriales, family_Bifidobacteriaceae, and genus_Alistipes exhibited a negative correlation, whereas genus_CandidatusSoleaferrea showed a positive correlation. Concerning the left bundle-branch block (LBBB), family_Peptococcaceae appeared to decrease the risk, while genus_Flavonifractor was linked to an increased risk. Lastly, no causative GM was identified in the right bundle-branch block (RBBB) context. We have uncovered potential causal links between some GM, arrhythmias, and conduction blocks. This insight may aid in designing microbiome-based interventions for these conditions and their risk factors in future trials. Additionally, it could facilitate the discovery of novel biomarkers for targeted prevention strategies.

Racial and Ethnic Differences in Studies of the Gut Microbiome and Osteoporosis.

The purpose of this review is to summarize the scientific evidence published in the past 5 years examining the epidemiology of bone health as it relates to the gut microbiome, across race and ethnicity groups. The link between the gut microbiome and bone health is well established and is supported by numerous biological mechanisms. However, human study research in this field is dominated by studies of older adults residing in Asian countries. A limited number of epidemiological and randomized controlled trials have been conducted with individuals in other countries; however, they are marked by their racial and ethnic homogeneity, use varied measures of the gut microbiome, and different interventions (where applicable), making comparisons across race and ethnic groups difficult. As the global prevalence of osteoporosis increases, the need for lifestyle interventions is critical. Existing data suggest that racial and ethnic differences in gut microbiome exist. Studies examining the relation between bone health and gut microbial structure and function across diverse racial and ethnic groups are needed to determine appropriate microbiome-based interventions.

Exploring the oral microbiome: an updated multidisciplinary oral healthcare perspective.

The oral cavity is home to diverse microbial content, collectively called as the oral microbiome. The latest technological advancements have unraveled the intricacies of the oral microbiome. It can be of great importance for oral health care givers to know the fundamentals and latest developments in the field of the oral microbiome, as oral dysbiosis is associated with many common diseases frequently seen and managed by them. These diseases include dental caries, periodontitis, mucosal diseases (such as oral leukoplakia, oral lichen planus, and systemic lupus erythematosus), oral cancers, and even co-infections related to the current COVID-19 pandemic. The emergence of new genomic and molecular biology methodologies has been pivotal for understanding the role of the human microbiome in health and disease. The current review compiles oral microbiome in health and disease with a multidisciplinary dental approach. The insight into the oral microbiome, which is provided dental specialty wise in the current article will initiate and guide researchers of various disciplines in developing microbiome-based therapeutic or prophylactic management strategies, managing public health challenges by microbiome-based boarder interventions and divert resources for preserving and achieving a balanced oral microbiome.

Assessing the Performance of a Novel Stool-Based Microbiome Test That Predicts Response to First Line Immune Checkpoint Inhibitors in Multiple Cancer Types

The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice.

Characterization of gut microbiota associated with metabolic syndrome and type-2 diabetes mellitus in Mexican pediatric subjects

BackgroundChildhood obesity is a serious public health concern that confers a greater risk of developing important comorbidities such as MetS and T2DM. Recent studies evidence that gut microbiota may be a contributing factor; however, only few studies exist in school-age children. Understanding the potential role of gut microbiota in MetS and T2DM pathophysiology from early stages of life might contribute to innovative gut microbiome-based interventions that may improve public health. The main objective of the present study was to characterize and compare gut bacteria of T2DM and MetS children against control subjects and determine which microorganisms might be potentially related with cardiometabolic risk factors to propose gut microbial biomarkers that characterize these conditions for future development of pre-diagnostic tools.ResultsStool samples from 21 children with T2DM, 25 with MetS, and 20 controls (n = 66) were collected and processed to conduct 16S rDNA gene sequencing. α- and β-diversity were studied to detect microbial differences among studied groups. Spearman correlation was used to analyze possible associations between gut microbiota and cardiometabolic risk factors, and linear discriminant analyses (LDA) were conducted to determine potential gut bacterial biomarkers. T2DM and MetS showed significant changes in their gut microbiota at genus and family level. Read relative abundance of Faecalibacterium and Oscillospora was significantly higher in MetS and an increasing trend of Prevotella and Dorea was observed from the control group towards T2DM. Positive correlations were found between Prevotella, Dorea, Faecalibacterium, and Lactobacillus with hypertension, abdominal obesity, high glucose levels, and high triglyceride levels. LDA demonstrated the relevance of studying least abundant microbial communities to find specific microbial communities that were characteristic of each studied health condition.ConclusionsGut microbiota was different at family and genus taxonomic levels among controls, MetS, and T2DM study groups within children from 7 to 17 years old, and some communities seemed to be correlated with relevant subjects’ metadata. LDA helped to find potential microbial biomarkers, providing new insights regarding pediatric gut microbiota and its possible use in the future development of gut microbiome-based predictive algorithms.

The Local Tumor Microbiome Is Associated with Survival in Late-Stage Colorectal Cancer Patients.

The gut microbiome is associated with survival in colorectal cancer. Single organisms have been identified as markers of poor prognosis. However, in situ imaging of tumors demonstrate a polymicrobial tumor-associated community. To understand the role of these polymicrobial communities in survival, we conducted a nested case-control study in late-stage cancer patients undergoing resection for primary adenocarcinoma. The microbiome of paired tumor and adjacent normal tissue samples was profiled using 16S rRNA sequencing. We found a consistent difference in the microbiome between paired tumor and adjacent tissue, despite strong individual microbial identities. Furthermore, a larger difference between normal and tumor tissue was associated with prognosis: patients with shorter survival had a larger difference between normal and tumor tissue. Within the tumor tissue, we identified a 39-member community statistic associated with survival; for every log2-fold increase in this value, an individual's odds of survival increased by 20% (odds ratio survival 1.20; 95% confidence interval = 1.04 to 1.33). Our results suggest that a polymicrobial tumor-specific microbiome is associated with survival in late-stage colorectal cancer patients. IMPORTANCE Microbiome studies in colorectal cancer (CRC) have primarily focused on the role of single organisms in cancer progression. Recent work has identified specific organisms throughout the intestinal tract, which may affect survival; however, the results are inconsistent. We found differences between the tumor microbiome and the microbiome of the rest of the intestine in patients, and the magnitude of this difference was associated with survival, or, the more like a healthy gut a tumor looked, the better a patient's prognosis. Our results suggest that future microbiome-based interventions to affect survival in CRC will need to target the tumor community.

Oral microbiome correlates with selected clinical biomarkers in individuals with no significant systemic disease.

The oral microbiome is an important component of the microbiome in the human body. Although the association of the oral microbiome with various diseases, including periodontitis and cancer, has been reported, information on how the oral microbiome is related to health-related indicators in healthy populations is still insufficient. In this study, we examined the associations of the oral microbiome with 15 metabolic and 19 complete blood count (CBC)-based markers in 692 healthy Korean individuals. The richness of the oral microbiome was associated with four CBC markers and one metabolic marker. Compositional variation in the oral microbiome was significantly explained by four markers: fasting glucose, fasting insulin, white blood cell count, and total leukocyte count. Furthermore, we found that these biomarkers were associated with the relative abundances of numerous microbial genera, such as Treponema, TG5, and Tannerella. By identifying the relationship between the oral microbiome and clinical biomarkers in a healthy population, our study presents a direction for future studies on oral microbiome-based diagnosis and interventions.

Gut microbiota in relation to frailty and clinical outcomes.

The gut microbiota is involved in several aspects of host health and disease, but its role is far from fully understood. This review aims to unveil the role of our microbial community in relation to frailty and clinical outcomes. Ageing, that is the continuous process of physiological changes that begin in early adulthood, is mainly driven by interactions between biotic and environmental factors, also involving the gut microbiota. Indeed, our gut microbial counterpart undergoes considerable compositional and functional changes across the lifespan, and ageing-related processes may be responsible for - and due to - its alterations during elderhood. In particular, a dysbiotic gut microbiota in the elderly population has been associated with the development and progression of several age-related disorders. Here, we first provide an overview of the lifespan trajectory of the gut microbiota in both health and disease. Then, we specifically focus on the relationship between gut microbiota and frailty syndrome, that is one of the major age-related burdens. Finally, examples of microbiome-based precision interventions, mainly dietary, prebiotic and probiotic ones, are discussed as tools to ameliorate the symptoms of frailty and its overlapping conditions (e.g. sarcopenia), with the ultimate goal of actually contributing to healthy ageing and hopefully promoting longevity.