Gut Microbiota Research Articles

Inflammatory bowel diseases: epidemiology and risk factors (review)

The global spread of IBD is likely due to the westernization of the diet and the environment, which leads to changes in the gut microbiome and increases the risk of disease in people with a genetic predisposition. In light of the increasing incidence of IBD worldwide, it is important to evaluate risk factors in order to develop prognostic risk models for IBD and various variants of the course of UC and CD and methods to combat these diseases. This review article examines key aspects related to the negative and beneficial effects of various factors on the development and course of IBD. The data shows that smoking (OR = 1.76; 95% CI: 1.40–2.22), obesity class II or III (OR = 1.86; 95% CI: 1.30–2.68 for CD and OR = 2.97; 95% CI: 1.75–5.17), taking antibiotics one year before the diagnosis (OR = 1.61;95% CI: 1.26–2.05 for UC and OR = 1.20; 95% CI: 1.09–1.31 for CD), nonsteroidal anti-inflammatory drugs (Relative Risk (RR) = 1.53; 95% CI: 1.08–2.16 for UC), combined oral contraceptives (UC by 3.3%; 95% ДИ: 2.1–4.4 and CD by 6.4%; 95% ДИ: 5.1–7.7), can not only increase the risks of exacerbations of IBD, but also contribute to the development of these conditions. These factors can aggravate the course of an existing disease: for example, the frequency of hospitalizations (OR = 2.35; 95% CI: 1.56–3.52) and the probability of resistance to genetically engineered biological drugs (GEBD) (OR = 1.6; 95% CI: 1.39–1.83). Dietary factors such as ultra-processed foods (RR = 1.82; 95% CI: 1.22–2.72), confectionery (≥ 100 g/day) (RR = 2.58; 95% CI: 1.44–4.62) and trans fats (RR = 1.34; 95% CI: 0.94–1.92) can have a negative impact, increasing the risk of developing IBD. Physical activity is considered as factors that have a protective effect on the course of IBD, reducing the frequency of exacerbations (RR = 0.78; 95% CI: 0.54–1.13 for UC and RR = 0.72; 95% CI: 0.55–0.94 for CD). Dietary fiber (24 g/day) reduces the risk of developing CD (RR = 0.59; 95% CI:0.39–0.90), and a large number of fruits in the diet reduces the risk of developing both UC (OR = 0.69; 95% CI: 0.49–0.96) and CD (OR = 0.57; 95% CI: 0.44–0.74).

Roles of traditional Chinese medicine extracts in hyperuricemia and gout treatment: Mechanisms and clinical applications

In this manuscript, we comment on the article by Liu et al published in the recent issue of the journal. Hyperuricemia (HUA) has become the second most common metabolic disease after type 2 diabetes mellitus and is the most important risk factor for gout. This discussion focuses on the targets and clinical application value of traditional Chinese medicine (TCM) extracts in the treatment of HUA and gout, emphasizing the role of gut microbiota. Liu et al ’s study demonstrated that Poecilobdella manillensis protein extract alleviated HUA through multiple mechanisms, including inhibition of uric acid (UA) reabsorption, promotion of UA excretion, repair of intestinal barrier function, and regulation of gut microbiota and metabolome. Unlike the commonly used urate-lowering drugs such as allopurinol and febuxostat, which have clear and single targets, many TCMs have multi-target effects. However, the active components and mechanisms of TCMs are not fully understood, limiting their clinical application in the treatment of HUA and gout. Additionally, the role of gut microbiota in UA metabolic homeostasis needs to be further explored.

Modulation of Gut Microbiota Composition and Microbial Phenolic Catabolism of Phenolic Compounds from Achillea millefolium L. and Origanum majorana L.

The impact of the nonbioaccessible fraction of two phenolic-rich extracts from Achillea millefolium L. (yarrow) and Origanum majorana L. (marjoram) on the modulation of the human gut microbiota was investigated in vitro. Microbial metabolism of the phenolic compounds was also addressed. In general, phenolic acids or O-glycosidic flavones quickly disappeared, in contrast to methoxy- or C-glycosidic flavonoids. This colonic metabolism yielded phloroglucinol, 3,4-dimethoxyphenylacetic acid, 3-(4-hydroxyphenyl)-propionic acid, and 4-hydroxybenzoic acid as the main metabolites of the microbial catabolism of rosmarinic acid or caffeoylquinic acids, among others. The 16S rRNA gene sequencing showed that the most promising modulatory effect was related to the increase in Bifidobacterium spp., Collinsella spp., Romboutsia, and Akkermansia muciniphila for both plant extracts, along with Blautia spp. and Dialister for yarrow extract. This beneficial modulation was accompanied by the increase in butyric acid production, highlighting the potential prebiotic-like effect on the gut microbiota of these two previously unstudied edible plants.

Pediococcus acidilactici Y01 reduces HFD-induced obesity via altering gut microbiota and metabolomic profiles and modulating adipose tissue macrophage M1/M2 polarization.

Obesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.

Relationship between fermented dairy consumption, gut microbiota and type 2 diabetes.

Relationship between fermented dairy consumption, gut microbiota and type 2 diabetes.

Population Dynamics and the Microbiome in a Wild Boreal Mammal: The Snowshoe Hare Cycle and Impacts of Diet, Season and Predation Risk.

The North American boreal forest is a massive ecosystem, and its keystone herbivore is the snowshoe hare (Lepus americanus). Hares are exposed to considerable environmental extremes in diet and weather, food availability, and predation risk. Gut microbiomes have been suggested to facilitate adaptive animal responses to environmental change, but severe environmental challenges to homeostasis can also disrupt host-microbiome relationships. To better understand gut microbiome contributions to animal acclimation, we studied the faecal bacterial microbiome of wild hares across two types of extreme environmental change that are integral to their natural history: (1) seasonal transitions between summer and winter, and (2) changes over the ~10 year 'boom-bust' population cycles that are characterised by shifting food resource availability and predation pressure. When compared to summer, hares in winter had lower bacterial richness and were depleted in 20 families (including Oxalobacteraceae and Christensenellaceae) but enriched for Ruminococcaceae (a family which contains plant fibre degrading bacteria) alongside nine other bacterial groups. Marked bacterial microbiome differences also occurred across phases of the population cycle. Bacterial microbiomes were lower in richness and compositionally distinct in the peak compared to the increase or decline phases of the population cycle. Direct measures of host physiology and diet quality (faecal fibre contents) most strongly supported food resource availability as a mechanism underlying phase-based differences in bacterial communities, but faecal fibre contents could not fully account for bacterial microbiome variation across phases.

The cow GUTBIOME CY study: investigating the composition of the cattle gut microbiome in health and infectious disease transmission in cyprus

BackgroundRecent evidence suggests that the lower gut microbiome of ruminants presents roles in their health and environment, including the development of the mucosal immune system, milk production efficiency and quality and subsequent methane emissions. However, there are proportionately fewer studies on this complex microbial community in cattle and region-focus studies are non- existent.MethodsHerein, we present the research protocol of the GUTBIOME CY project pertaining to determine the composition of the lower gut microbiome in dairy cows situated in 37 farms across five districts of the island of Cyprus. Detailed questionnaires on animal husbandry and farming practices will be gathered from each farm. Faecal, milk (individual and bulk) and water samples will also be collected from cows and their offspring. Samples will be analysed using a combination of molecular biology and bioinformatics pipelines to define microbiome profiles and antimicrobial resistance (AMR). Information collected from the questionnaires will be used to test for associations between animal husbandry or farming practices and microbiome components and AMR.DiscussionCollected samples will establish the first dairy cattle biobank in the country for contributing substantially towards scientific advancements in microbiome research and providing insights to all stakeholders, tailored to the unique agricultural context of Cyprus.

Statin Use and Hyperglycemia: Do Statins Cause Diabetes?

Atherosclerotic cardiovascular disease (ASCVD) and diabetes are leading causes of morbidity and mortality in the United States and globally. Statin medications, a cornerstone of ASCVD prevention and treatment strategies, have been demonstrated to cause hyperglycemia and new onset diabetes mellitus (NODM). The purpose of this review is to summarize existing and emerging knowledge around the intersection of statins and these two important clinical problems. Since initial reporting of statin-induced hyperglycemia and NODM, the totality of available data corroborates an association between incident diabetes and statin use. A consensus that high-intensity statin and individuals with obesity or glycemic parameters approximating diabetes thresholds constitute the majority of risk exists. Alterations in insulin signaling, glucose transport and gastrointestinal microbiota are leading hypotheses underlying the mechanisms of statin-induced hyperglycemia. The probability of NODM based on an individual's risk factors and statin specific properties can be anticipated. This risk needs to be contextualized with the risk of ASCVD. In order to effectively adjudicate the risk of NODM, improvement in formulating and ultimately conveying a comprehensive ASCVD risk assessment to patients is necessary.

Metagenomic analysis reveals the community composition of the microbiome in different segments of the digestive tract in donkeys and cows: implications for microbiome research

IntroductionThe intestinal microbiota plays a crucial role in health and disease. This study aimed to assess the composition and functional diversity of the intestinal microbiota in donkeys and cows by examining samples collected from different segments of the digestive tract using two distinct techniques: direct swab sampling and faecal sampling.ResultsIn this study, we investigated and compared the effects of multiple factors on the composition and function of the intestinal microbial community. Approximately 300 GB of metagenomic sequencing data from 91 samples obtained from various segments of the digestive tract were used, including swabs and faecal samples from monogastric animals (donkeys) and polygastric animals (cows). We assembled 4,004,115 contigs for cows and 2,938,653 contigs for donkeys, with a total of 9,060,744 genes. Our analysis revealed that, compared with faecal samples, swab samples presented a greater abundance of Bacteroidetes, whereas faecal samples presented a greater abundance of Firmicutes. Additionally, we observed significant variations in microbial composition among different digestive tract segments in both animals. Our study identified key bacterial species and pathways via different methods and provided evidence that multiple factors can influence the microbial composition. These findings provide new insights for the accurate characterization of the composition and function of the gut microbiota in microbiome research.ConclusionsThe results obtained by both sampling methods in the present study revealed that the composition and function of the intestinal microbiota in donkeys and cows exhibit species-specific and region-specific differences. These findings highlight the importance of using standardized sampling protocols to ensure accurate and consistent characterization of the intestinal microbiota in various animal species. The implications and underlying mechanisms of these associations provide multiple perspectives for future microbiome research.

Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway.

Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.

Exploring the gut-brain axis in alzheimer’s disease treatment via probiotics: evidence from animal studies-a systematic review and meta-analysis

IntroductionAlzheimer’s disease (AD) is a prevalent neurodegenerative disorder in the elderly, causing cognitive impairment. Its pathogenesis is characterized by amyloid beta deposition, neurofibrillary tangles, and neuroinflammation. Recent research has identified the link between gut dysbiosis, an imbalance of intestinal microorganisms, to this pathogenesis via the gut-brain axis. This study aims to review the probiotics’ therapeutic effect, targeting the gut-brain axis, for AD treatment in animals.MethodsThe method utilized in this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Three reviewers searched articles through PubMed, Scopus, and Embase using advanced search strategy. Articles published between 2010 and 2023 that met the criteria were included.ResultsOf 2,273 articles, 21 animal studies measuring the effects of probiotics genera Lactobacillus and/or Bifidobacterium on AD via at least one of these four outcomes: AD pathology, cognitive function, neuroinflammation, and gut microbiota composition. The results demonstrated that probiotics could repair gut dysbiosis by decreasing pro-inflammatory bacteria and increasing anti-inflammatory bacteria. Repaired dysbiosis was found to be associated with less neuroinflammation as significant reductions in neuroinflammatory markers related to the pathogenesis of AD such as TNF-α (SMD = -2.08, P = 0.005), IL-6 (SMD = -2.98, P < 0.0005), and IL-1β (SMD = -2.49, P = 0.003) were observed. Reduced amyloid beta deposition (SMD = -1.17, P = 0.009) was reported, but reduction in tau hyperphosphorylation was found to be insignificant. For cognitive function, positive results were demonstrated for all three aspects of cognitive function including long-term memory (SMD = 2.55, P < 0.00001), short-term memory (SMD = 1.32, P = 0.003), and spatial recognition (SMD = -1.13, P < 0.00001).ConclusionsParticular formulas of probiotics showed potential effectiveness in AD therapies with demonstrated association with the gut-brain axis. Future studies are required to investigate strain-specific results and optimal dosages and regimens.

MicroRNA signatures in neuroplasticity, neuroinflammation and neurotransmission in association with depression.

Depression is a multifactorial disorder that occurs mainly on account of the dysregulation of neuroplasticity, neurotransmission and neuroinflammation in the brain. In addition to environmental /lifestyle factors, the pathogenesis of disease has been associated with genetic and epigenetic factors that affect the reprogramming of normal brain function. MicroRNA (miRNAs), a type of non-coding RNAs, are emerging as significant players that play a vital role in the regulation of gene expression and have been extensively explored in neurodegenerative disorders. Recent studies have also shown the role of gut microbiota that forms a complex bidirectional network with gut brain axis, impacting neuroinflammation in case of Parkinson's disease and depression. Translating targeted miRNA-based therapies for the treatment of neurological disorders including depression, into clinical practice remains challenging due to the ineffective delivery of the therapeutic molecules and off-target effects of the specific miRNAs. This review provides significant insights into how miRNAs are emerging as vital players in the development of depression, especially the ones involved in three important processes including neuroplasticity, neurotransmission and neuroinflammation. In this review, the current status of miRNAs as biomarkers for therapeutic interventions in the case of depression has been discussed along with an overview of future perspectives, like use of nanotechnology and gene editing, keeping in view other multifactorial disorders where such interventions by mimics and inhibitors have already reached clinical trials. The challenges for targeting the specific miRNAs for therapeutic outcomes have also been highlighted.

Identification of novel fructo-oligosaccharide bacterial consumers by pulse metatranscriptomics in a human stool sample.

Complex carbohydrates are key contributors to the composition of the human gut microbiota and play an essential role in the microbiota's effects on host health. Understanding which bacteria consume complex carbohydrates, or glycans, provides a mechanistic link between dietary prebiotics and their beneficial health effects, an essential step for their therapeutic application. Here, we used a pulse metatranscriptomics pipeline to identify bacterial consumers based on glycan metabolism induction in a human stool sample. We identified novel consumers of fructo-oligosaccharide among Blautia species, expanding our understanding of this well-known glycan. Our approach can be applied to identify consumers of understudied glycans and expand our prebiotic repertoire. It can also be used to study prebiotic glycans directly in stool samples in distinct patient populations to help delineate the prebiotic mechanism.

The healthy human gut can take it all: vancomycin-variable, linezolid-resistant strains and specific bacteriocin-species interplay in Enterococcus spp.

Enterococcus spp. are opportunistic human pathogens colonizing the human gut and a significant reservoir for the continuous adaptation of hospital clones. However, studies on the features of enterococci species co-colonizing healthy individuals are scarce. We investigated the prevalence, antibiotic resistance, and bacteriocin profiles of Enterococcus species in fecal samples from healthy adults in Portugal using culture-based methods, WGS, and bacteriocin inhibition assays. Results were compared with data from a 2001 study in the same region. Enterococcus spp. (n = 315; 24% MDR) were recovered from all volunteers. Enterococcus lactis was the prevalent species (75%), followed by Enterococcus faecalis (65%) and Enterococcus faecium (47%). E. lactis prevalence increased 2.5-fold since 2001. Linezolid resistance genes (optrA/poxtA) were detected in E. faecium and Enterococcus thailandicus isolates, while a vancomycin-variable E. faecium was also identified. Virulence and plasmid profiles were diverse across species, with evidence of exchange of virulence markers and plasmid replicons between E. faecium and E. lactis. Bacteriocin gene repertoires were extensive and species-specific. Higher numbers of bacteriocin genes were associated with stronger inhibition profiles, and 25% of E. faecium and E. lactis isolates were capable of inhibiting relevant VRE clones. This study unveils the co-occurrence and ecological dynamics of Enterococcus species in the healthy human gut, reinforcing its role as a reservoir for key antibiotic resistance genes and potentially pathogenic strains. The shift toward E. lactis prevalence and the detection of linezolid resistance genes in healthy individuals underscore the need for ongoing surveillance of the gut microbiome to guide public health strategies and antibiotic stewardship efforts.IMPORTANCEThis study highlights the role of Enterococcus species in the healthy human gut, revealing important insights into their prevalence and antibiotic resistance. It emphasizes that the human gut serves as a significant reservoir for antibiotic-resistant strains and shows a notable increase and prevalence of Enterococcus lactis, which has been underappreciated due to identification challenges. The research also underscores the bacteriocins' role in microbial competition, where commensal strains inhibit clinical VRE, potentially aiding the restoration of the gut microbiota, after antibiotic treatment. The findings accentuate the need for ongoing surveillance to track changes in gut bacteria, especially with the emergence of resistance genes to last resort antibiotics. Such monitoring is crucial for shaping public health strategies and managing the growing threat of antibiotic-resistant infections. Profiling bacteriocins at the species and strain level can identify ecological adaptation factors and inform strategies to target high-risk clones.

Clinical Study of Limosilactobacillus reuteri for the Treatment of Children with Chronic Tic Disorders/Tourette Syndrome: A Mid-Term Efficacy Evaluation.

Gut microbiota plays an important role in tic disorders (TDs); however, clinical research on probiotics for chronic TDs treatment is lacking. We aimed to investigate the effectiveness of probiotics, hypothesizing that their clinical efficacy is comparable to that of clonidine in treating chronic TDs. Patients were randomly assigned to receive either Limosilactobacillus reuteri or clonidine transdermal patch treatment for 8weeks while maintaining their existing treatment. The Yale Global Tic Severity Scale (YGTSS); Swanson, Nolan, and Pelham-IV Scale (SNAP-IV); and Child Behavior Check List (CBCL) scores were assessed before and after treatment. We matched the patients in both groups for age, sex, age at onset, and tic type. A significant improvement in YGTSS scores was observed in both groups (p = 0.024). The improvement in attention deficits on the SNAP-IV scale was similar between the two groups, with no significant difference (p = 0.465). For hyperactivity disorder, after matching patients in both groups for age, sex, age at onset, tic type, and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores, a significant difference in improvement was observed between the groups (p = 0.010), with the probiotics group showing greater improvement (0.3 ± 0.58 vs. 0.1 ± 0.50). At 9weeks, social ability on the CBCL scale increased by 3.2 ± 6.26 from baseline in the probiotics group and by 0.6 ± 4.07 in the clonidine group, with a significant difference between the two (p = 0.049). Although there was no significant difference in behavioral problems between the two groups (p = 0.347), the trend of improvement was more pronounced in the probiotics group than in the clonidine group (12.7 ± 25.86 vs. 8.4 ± 13.15). The mid-term efficacy evaluation demonstrated that L.reuteri, when added to the treatment of children with chronic TDs, was more effective in improving tic symptoms than clonidine transdermal patch treatment. Additionally, it provided moderate improvement in hyperactivity symptoms. chictr.org.cn (registration numbers ChiCTR2200056708, ChiCTR2200056578).

Multi-level analysis of gut microbiome extracellular vesicles-host interaction reveals a connection to gut-brain axis signaling.

Microbiota-released extracellular vesicles (MEVs) have emerged as a key player in intercellular signaling. In this study, a multi-level analysis revealed presence of a diverse array of biologically active molecules encapsulated within MEVs, including neuroactive metabolites, such as arachidonyl-dopamine, gabapentin, glutamate, and N-acylethanolamines, and gamma-aminobutyric acid (GABA). Metaproteomics also unveiled an enrichment of neural-related proteins, mainly the glutamine/glutamate/GABA pathway. MEVs were able to cross epithelial and blood-brain barriers in vitro. RNA-seq analyses showed that MEVs stimulate several immune pathways while suppressing cell apoptosis process. Furthermore, MEVs were able to traverse the intestinal barriers and reach distal organs, including the brain, thereby potentially influencing brain functionality and contributing to mental and behavior.

Difference in fecal and oral microbiota between pancreatic cancer and benign/low-grade malignant tumor patients

BackgroundSignificant gaps exist in understanding the gastrointestinal microbiota in patients with pancreatic cancer (PCA) versus benign or low-grade malignant pancreatic tumors (NPCA). This study aimed to analyze these microbiota characteristics and explore their potential use in distinguishing malignant pancreatic lesions.MethodsBetween September 2020 and May 2024, fecal and oral samples were collected from 121 patients undergoing surgical resection or diagnostic biopsy of pancreatic lesions, including 75 patients with PCA and 46 patients with NPCA, and 16s rRNA sequencing was performed. Random forest models based using fecal and oral microbiota data were developed to diagnose PCA and NPCA, with performance assessed using the leave-one-out cross validation method.ResultsThe Shannon index and PCoA analysis revealed significant differences in oral microbiota composition between PCA and NPCA (p < 0.001 and p = 0.001, respectively). Fecal microbiome richness differed significantly (p = 0.02), though composition similarity was noted (p = 0.238). LEfSe identified 16 and 23 genera with significant differences in fecal and oral microbiomes, respectively. Random forest classifiers based on fecal and oral microbiota achieved areas under the curves (AUCs) of 89.4% and 96.3%, respectively, for distinguishing PCA and NPCA. In the mucinous tumor cohort, oral and fecal microbiome classifiers outperformed CA19-9, yielding AUCs of 83.0% and 85.2%, respectively.ConclusionFecal and oral microbiota compositions were significantly different between PCA and NPCA patients. Random forest classifiers utilizing fecal and oral microbiota data effectively distinguish between benign or low-grade malignant and malignant pancreatic lesions.

Causal relationship between gut microbiota and lung squamous cell carcinoma: a bidirectional two-sample Mendelian randomization study.

This study aims to explore the potential causal relationship between gut microbiota and lung squamous cell carcinoma (LUSC). A bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) data from gut microbiota and LUSC. Gut microbiota served as the exposure factor, with instrumental variables selected from a GWAS involving 18 340 participants. LUSC data were drawn from a European cohort including 29 266 LUSC cases and 56 450 controls. Inverse-variance weighted (IVW) method was used as the primary method, with the Benjamini-Hochberg method applied to adjust for multiple comparisons. An independent dataset (ieu-a-967, containing 3275 LUSC cases and 15 038 controls) was used for replication analysis to ensure robustness. IVW analysis found that Butyricicoccus (OR = 0.79, 95% CI: 0.63-0.99, P = .042) and Coprobacter (OR = 0.85, 95% CI: 0.74-0.97, P = .018) were significantly protective against LUSC. In contrast, Victivallis (OR = 1.11, 95% CI: 1.00-1.23, P = .045) and Ruminococcus (OR = 1.28, 95% CI: 1.03-1.60, P = .028) increased LUSC risk. Replication analysis in the independent dataset confirmed significant associations for Ruminococcus and Coprobacter. No reverse causality or pleiotropy was detected. This study provides evidence of a causal relationship between specific gut microbiota and LUSC risk, highlighting new microbial targets for potential prevention and treatment strategies in lung cancer. Key messages What is already known on this topic? Previous studies have suggested potential links between gut microbiota composition and the development of various cancers, including lung cancer. However, the exact causal relationship between specific gut microbiota and lung squamous cell carcinoma (LUSC) has remained unclear. Traditional observational studies have struggled to determine the direction of causality due to confounding factors, making further investigation necessary through more robust methods such as Mendelian randomization (MR). What this study adds? This bidirectional MR study provides novel genetic evidence indicating that certain gut microbiotas are causally associated with LUSC risk. Specifically, Butyricicoccus appears to reduce the risk of LUSC, while Victivallis increases the risk. These findings highlight the role of the gut-lung axis in LUSC and open up new avenues for exploring gut microbiota as potential modulators of lung cancer risk. How this study might affect research, practice, or policy? The implications of this study may significantly influence future research into cancer prevention strategies by targeting gut microbiota. Additionally, it could inform clinical practices aimed at modulating gut microbiota to lower the risk of LUSC, potentially influencing dietary or probiotic interventions to reduce cancer susceptibility. Furthermore, these results might shape public health policies that focus on the gut-lung axis as a novel avenue for cancer prevention and management.

The role of gut microbiota and metabolomic pathways in modulating the efficacy of SSRIs for major depressive disorder

This study aims to explore the mechanism by which gut microbiota influences the antidepressant effects of serotonin reuptake inhibitors (SSRIs) through metabolic pathways. A total of 126 patients were analyzed for their gut microbiota and metabolomics. Patients received SSRI treatment and were categorized into responder and non-responder groups based on changes in their Hamilton Depression Rating Scale (HAMD-17) scores before and after treatment. The association between gut microbiota composition and the efficacy of SSRIs was investigated through 16S rRNA gene sequencing and metabolomic analysis, and a predictive model was developed. As a result, the study found significant differences in gut microbiota composition between the responder and resistant groups. Specific taxa, such as Ruminococcus, Bifidobacterium, and Faecalibacterium, were more abundant in the responder group. Functional analysis revealed upregulation of acetate degradation and neurotransmitter synthesis pathways in the responder group. The machine learning model indicated that gut microbiota and metabolites are potential biomarkers for predicting SSRIs efficacy. In conclusion, gut microbiota influences the antidepressant effects of SSRIs through metabolic pathways. The diversity and function of gut microbiota can serve as biomarkers for predicting the treatment response, providing new insights for personalized treatment.

Exploring the influence of age and diet on gut microbiota development in children during the first 5 years: a study from Yaoundé, Cameroon

IntroductionThe development of the human gut microbiota is shaped by factors like delivery mode, infant feeding practices, maternal diet, and environmental conditions. Diet plays a pivotal role in determining the diversity and composition of the gut microbiome, which in turn impacts immune development and overall health during this critical period. The early years, which are vital for microbial shaping, highlight a gap in understanding how the shift from milk-based diets to solid foods influences gut microbiota development in infants and young children, particularly in Yaoundé, Cameroon.MethodsThis study involved an analysis of the gut microbiota composition in 70 children aged ≤5 years through 16S rDNA gene metagenomic sequencing of fecal metagenomic DNA. The participants were grouped into four age categories: 0–6 months, 7–12 months, 13–24 months, and 25–60 months.ResultsWe observed a reduction in microbial diversity in the younger age groups, which increased progressively with age. At the taxonomic level, our analysis identified Firmicutes as the predominant phylum, with its abundance rising in older age groups, suggesting a maturation of the microbiota characterized by distinct genera associations. In the 0–6 month age group, we noted an enrichment of Lactobacilli and Bifidobacteria, which may play a crucial role in modulating and supporting immune system development during infancy. After 6 months, we found a higher prevalence of Clostridium, Bacillus, Roseburia, and Faecalibacterium, which are associated with fiber fermentation and the production of short-chain fatty acids (SCFAs).ConclusionThese findings underscore the influence of milk products and complementary diets on gut microbiota across various age groups, promoting increased diversity essential for healthy gut development. More such studies in the LMICs would augment and strengthen understanding towards functional microbiome.