Gut Microbiota Research Articles

Integrative review of the gut microbiome’s role in pain management for orthopaedic conditions

The gut microbiome, a complex ecosystem of microorganisms, has a significant role in modulating pain, particularly within orthopaedic conditions. Its impact on immune and neurological functions is underscored by the gut-brain axis, which influences inflammation, pain perception, and systemic immune responses. This integrative review examines current research on how gut dysbiosis is associated with various pain pathways, notably nociceptive and neuroinflammatory mechanisms linked to central sensitization. We highlight advancements in meta-omics technologies, such as metagenomics and metaproteomics, which deepen our understanding of microbiome-host interactions and their implications in pain. Recent studies emphasize that gut-derived short-chain fatty acids and microbial metabolites play roles in modulating neuroinflammation and nociception, contributing to pain management. Probiotics, prebiotics, synbiotics, and faecal microbiome transplants are explored as potential therapeutic strategies to alleviate pain through gut microbiome modulation, offering an adjunct or alternative to opioids. However, variability in individual microbiomes poses challenges to standardizing these treatments, necessitating further rigorous clinical trials. A multidisciplinary approach combining microbiology, immunology, neurology, and orthopaedics is essential to develop innovative, personalized pain management strategies rooted in gut health, with potential to transform orthopaedic pain care.

Fecal microbiota transplantation in allergic diseases

Microorganisms such as bacteria, fungi, viruses, parasites living in the human intestine constitute the human intestinal microbiota. Dysbiosis refers to compositional and quantitative changes that negatively affect healthy gut microbiota. In recent years, with the demonstration that many diseases are associated with dysbiosis, treatment strategies targeting the correction of dysbiosis in the treatment of these diseases have begun to be investigated. Faecal microbiota transplantation (FMT) is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit. FMT studies have gained popularity after probiotic, prebiotic, symbiotic studies in the treatment of dysbiosis and related diseases. FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance (T helper 1/T helper 2 cells) and thus suppression of allergic responses. In this article, the definition, application, safety and use of FMT in allergic diseases will be discussed with current data.

Complex relationship between childhood obesity and the gut microbiota

Complex relationship between childhood obesity and the gut microbiota

Integrated multi-omics analysis reveals that Gongying San ameliorates subclinical mastitis by modulating intestinal microbiota and metabolites in dairy cows

IntroductionSubclinical mastitis (SCM) is a common disease in dairy cows associated with dysbiosis of the gastrointestinal microbiota and systemic inflammatory response. Gongying San (GYS), a commonly used herbal formula for the treatment of mastitis, has anti-inflammatory, antibacterial and antioxidant effects, but the underlying mechanisms remain unknown. Therefore, we performed a multi-omics analysis to determine the effects of GYS on intestinal microbiota and metabolites in cows with SCM.MethodsA total of 32 Holstein cows were divided into four groups of 8 cows each, including healthy control group, subclinical mastitis group, GYS treatment group (290 g/day) and ceftiofur treatment group (2.2 mg/kg bw).ResultsGYS significantly increased milk yield, lactose and milk protein, and decreased somatic cell count (SCC) in milk from cows with SCM. In the serum, GYS decreased the levels of lipopolysaccharide (LPS), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) and increased the concentration of superoxide dismutase (SOD). In addition, there was an increase in UCG-010 and Blautia and a decrease in Bacteroides, Lachnospiraceae, and Agathobacter in feces after GYS treatment. Fecal untargeted metabolomics showed that GYS supplementation mainly downregulated inflammation-related metabolism, including arachidonic acid and choline metabolism.DiscussionIn the treatment of SCM, GYS showed multi-target therapeutic advantages of anti-inflammatory, antioxidant and immunomodulatory properties compared to antibiotics. Bacteroides, Lachnospiraceae and UCG-010 may be involved in the regulation of inflammation through 3-oxo-Δ4bile acids and phosphatidylcholine.

Loss of Myostatin Alters Gut Microbiota and Carbohydrate Metabolism to Influence the Gut–Muscle Axis in Cattle

The gut–muscle axis plays a vital role in host metabolism and health. Although the MSTN gene is a well-known negative regulator of muscle growth, its role in intestinal function and metabolism remains unclear. Understanding this connection is crucial for revealing the systemic impact of MSTN gene editing and its potential to improve metabolic efficiency in livestock. In this study, we investigated the influence of MSTN deletion on gut microbiota composition and carbohydrate metabolism in the cecum and colon of cattle. Using integrated metagenomic, metabolomic, serum biochemical, and muscle transcriptomic analyses, we found significant alterations in microbial communities and key metabolic pathways. Hallella and Escherichia in the colon, as well as Alishewanella in the cecum, were closely linked to carbohydrate metabolism. Differential microbes and metabolites influenced key metabolic pathways, including glycolysis/gluconeogenesis and lipopolysaccharide biosynthesis. Functional gene analysis identified Bacteroides as the most critical bacterium affecting glycolysis/gluconeogenesis. Additionally, genes related to carbohydrate esterases were upregulated. These changes correlated with reduced serum glucose and insulin levels while increasing muscle gene expression related to glucose-to-lactose conversion. Overall, MSTN gene editing alters gut microbiota composition and carbohydrate metabolism in the cecum and colon, thereby influencing host glucose metabolism and energy homeostasis.

Serum proteins and faecal microbiota as potential biomarkers in newly diagnosed, treatment-naïve inflammatory bowel disease and irritable bowel syndrome patients.

Molecular biomarkers are valuable tools to predict the disease and determine its course. Several markers have been associated with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, none is sufficiently reliable to enable accurate diagnosis. We characterized a broad panel of serum proteins to assess disease-specific biomarker profiles and associate these findings with faecal microbiota composition in newly diagnosed IBD and IBS patients and healthy individuals. The study cohort consisted of 49 newly diagnosed treatment-naïve adult patients (13 Crohn's disease (CD), 13 ulcerative colitis (UC), and 23 IBS) and 12 healthy individuals. Inflammatory and metabolism-related serum proteins were assessed using PEA multiplex panels, while gut microbiota composition was determined by 16s rRNA gene amplicon sequencing. Serum proteins AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK were identified as markers with the most promising specificity/sensitivity and predictivity between healthy and disease groups, while IL-17A and TNFRSF9 enabled differentiation between IBD and IBS patients. Increased abundance of Enterobacteriaceae was associated with protein markers significantly elevated in IBD/IBS. In contrast, depletion of beneficial taxa like Ruminococcaceae and Verucomicrobiaceae (i.e. Akkermansia muciniphila) was associated with decrease of a set of markers in diseased groups. Differences in the abundance of Turicibacteriaceae were more predictive to discern CD from UC than any of the serum proteins investigated. By using a broad panel of inflammation and metabolism-related proteins, we determined serum markers with significantly different levels in treatment-naïve IBD and IBS patients compared to healthy individuals, as well as between IBD and IBS. KEY MESSAGES : Significant changes in the levels of several serum proteins and abundances of faecal bacterial taxa between study groups were found. Increased levels of AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK characterize both IBD and IBS, while IL-17A and TNFRSF9 differentiate IBD from IBS. Increase of Enterobacteriaceae and depletion of beneficial taxa Ruminococcaceae and Verucomicrobiaceae (i.e. Akkermansia muciniphila) was found in IBD and IBS. Differences in Turicibacteriaceae were more predictive to discern CD from UC than any of the serum proteins investigated.

Comparative analysis of oral, placental, and gut microbiota characteristics, functional features and microbial networks in healthy pregnant women.

Comparative analysis of oral, placental, and gut microbiota characteristics, functional features and microbial networks in healthy pregnant women.

Metabolites Mediate the Causal Associations Between Gut Microbiota and Chronic Kidney Disease: A Mendelian Randomization Study and Therapeutical Strategy from Traditional Chinese Medicine Perspective

Background: In chronic kidney disease (CKD), patients often suffer from intestinal barrier damage and gut microbiota disorders, characterized by reduced beneficial bacteria, increased harmful bacteria, and production of neurotoxins that worsen kidney damage. While associations between gut microbiota, plasma metabolites, and CKD have been observed, the causal relationships remain unclear and may be confounded by other factors. To address this, we used Mendelian randomization (MR) to investigate the causal effects of gut microbiota and plasma metabolites on CKD. Simultaneously, we explored the strategy of Traditional Chinese medicine to regulate the influence of gut microbiota mediated by serum metabolites on CKD. Methods: A two-sample MR study was conducted to evaluate the potential causal connections among gut microbiota, plasma metabolites, and CKD susceptibility. Gut microbiota data were obtained from the genome-wide association studies (GWASs) of gut microbiome composition by the Dutch Microbiome Project. CKD data were procured from the FinnGen biobank analysis, while comprehensive GWAS summary statistics for plasma metabolites were derived from the NHGRI-EBI GWAS Catalog. Fluctuations in gut microbiota and plasma metabolites in patients with CKD were evaluated using the weighted mode method. Additionally, pleiotropic and heterogeneity analyses were conducted to assess the reliability of the findings. Results: Twelve taxonomic and bacterial pathways and sixteen metabolites were found to be significantly associated with CKD. MR analysis revealed four causal relationships. Mediation analysis showed that arachidonoylcholine levels mediated the causal relationship between the enterobacterial common antigen biosynthesis pathway (ECASYN.PWY) and the risk of CKD, with a mediation proportion of 24.8%. X-12007 levels mediated the causal relationship between the aspartate superpathway (PWY0.781) and the risk of CKD, with a mediation proportion of 15.6%. N-acetyl-2-aminooctanoate levels mediated the relationship between tetrapyrrole biosynthesis II from glycine pathway (PWY.5189) and the risk of CKD, with a mediation proportion of 7.7%. X-22776 levels mediated the causal relationship between the superpathway of pyrimidine deoxyribonucleotides de novo Biosynthesis (PWY.7211) and the risk of CKD, with a mediation proportion of 23.8%. Conclusion: The current MR study provides evidence supporting potential causal relationships among specific gut microbiota taxa and pathways, plasma metabolite, and CKD. These findings offer novel perspectives for future research and the development of treatment and prevention strategies for CKD, as well as a scientific basis for traditional Chinese medicine intervention in the gut microbiota.

Causal relationship between gut microbiota, lipids, and neuropsychiatric disorders: A Mendelian randomization mediation study.

Causal relationship between gut microbiota, lipids, and neuropsychiatric disorders: A Mendelian randomization mediation study.

Perinatal bisphenol A exposure impairs gut microbial colonization: Implications for offspring obesity and neurodevelopment.

Perinatal bisphenol A exposure impairs gut microbial colonization: Implications for offspring obesity and neurodevelopment.

Causal link between gut microbiota and obsessive-compulsive disorder: A two-sample Mendelian randomization analysis.

Causal link between gut microbiota and obsessive-compulsive disorder: A two-sample Mendelian randomization analysis.

Nanocellulose dysregulated glucose homeostasis in female mice on a Western diet: The role of gut microbiome.

Nanocellulose dysregulated glucose homeostasis in female mice on a Western diet: The role of gut microbiome.

Gut microbiome changes in pediatric AML and association with event free survival.

10026 Background: Pediatric acute myeloid leukemia (AML) is characterized by months of hospitalization with a high risk for infections and a higher rate of relapse than many pediatric leukemias. Recent studies have highlighted the relationship between gut microbiome changes, long term cancer outcomes, and development of comorbidities. However, no study to date has examined the longitudinal changes in the gut microbiome in pediatric AML patients. Methods: In this retrospective study, longitudinal stool samples were taken from 14 pediatric patients with AML treated at Children’s Hospital Colorado. Sample collection started after initial diagnosis for 11 patients and after first relapse for 3 patients. These samples were analyzed using 16S ribosomal RNA (rRNA) gene sequencing along with clinical data extracted via manual chart review. Results: We found that the relative abundance of genus Fusobacterium was associated with relapses. Analysis indicated that Fusobacterium was significantly elevated in the stool of 3 of 6 newly diagnosed patients who relapsed within 5 years (using a linear model that also accounted for risk stratification based on genetics and treatment response (p = 0.03)). These patients had elevated Fusobacterium at multiple timepoints during treatment. Samples from the 5 newly diagnosed patients who did not relapse showed minimal Fusobacterium . Fusobacterium has previously been associated with other cancers, oncogenesis and immune evasion. Of the 14 patients, 5 experienced 1-4 cases of Streptococcus mitis bacteremia (SMB) during the sample collection period. Genus Streptococcus abundance in stool samples collected immediately prior to SMB did not correlate with positive blood cultures, although this genus was highly prevalent in the gut microbiome of patients with repeated episodes. Using mixed effects random forest model (MERFM) to broadly survey whether changes in any other gut bacteria predicted a positive SM blood culture, we found evidence for a negative relationship between SMB and change in relative abundance of genus Blautia , and a positive relationship with the genera Marvinbryantia, Anaerococcus, Parabacteroides and Dielma . This suggests that other aspects of microbiome composition may influence whether Streptococcus can translocate into the bloodstream. Of the 14 patients, 4 developed Clostridioides difficile infections (CDI) during the collection period. Increases in genus Clostridioides relative abundance occurred prior to clinical CDI. Using MERFM, Faith Phylogenetic Diversity was negatively related to development of CDI and presence of the genera Anarofustis, Bilophila, Alistipes and was positively related to CDI. Conclusions: These results show that the gut microbiome may be implicated or serve as a prognostic indicator for relapse in pediatric AML. Additionally, longitudinal gut microbiome changes in patients may be associated with various clinical complications.

In vitro digestion and fermentation characteristics of Agrocybe cylindracea polysaccharides and their interaction with the gut microbiota.

In vitro digestion and fermentation characteristics of Agrocybe cylindracea polysaccharides and their interaction with the gut microbiota.

Exploring the relationship between the gut microbiota and cognitive function in schizophrenia patients with distinct weights.

Exploring the relationship between the gut microbiota and cognitive function in schizophrenia patients with distinct weights.

Interaction of environmental fluoride exposure and gut microbes: Potential implication in the development of fluorosis in human subjects.

Interaction of environmental fluoride exposure and gut microbes: Potential implication in the development of fluorosis in human subjects.

Targeting gut-immune-heart modulate cardiac remodeling after acute myocardial infarction.

Targeting gut-immune-heart modulate cardiac remodeling after acute myocardial infarction.

The gut microbiome in pediatric diffuse midline gliomas: Correlative study results from the PNOC022 trial.

10015 Background: The gut microbiome exerts a multifaceted influence on treatment outcomes across various cancers, yet its potential role in diffuse midline gliomas (DMGs) remains under-explored. In this report, we present the gut microbiome findings from cohort 2 in the DMG–Adaptive Combination Trial (DMG-ACT, PNOC022). Methods: PNOC022 is an open-label, multi-institutional, international clinical trial using a Bayesian drug combination platform trial design. This report focuses on the combination therapy arm involving dordaviprone and paxalisib, administered to patients (aged 2–39 years) who had completed standard-of-care radiation therapy (Cohort 2). Stool samples were collected at baseline (n = 22), cycle 1 day 1 (n = 15), cycle 7 day 1 (n = 9), and at progression (n = 4). Microbiome profiling was performed with shotgun metagenomic sequencing (NovaSeq X Plus Series, PE150). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Longitudinal shifts in microbial communities were evaluated using α-diversity (Shannon-index) and β-diversity (Bray-Curtis dissimilarity index). Baseline α-diversity associations with PFS and OS were examined with log-rank tests and further validated through age-adjusted Cox regression analysis. Results: Between November 2021 and October 2023, 69 biopsy-confirmed DMG patients enrolled (median age 9 years [range 3-37], n = 42 female [61%]) in cohort 2. Median OS from time of diagnosis was 15.6 months (95% CI 12.9-19.5), with a median follow-up time of 19.5 months (95% CI 17.9-23.9). Microbiome analyses were performed for 33 DMG patients (48%). Alpha-diversity and β-diversity remained stable across timepoints. Using baseline samples (n = 22) and a median α-diversity cutoff of the respective group’s values, patients were stratified into two categories (low- vs. high-diversity). Low-diversity was associated with significantly worse PFS and trended worse for OS, resulting in a 6-month PFS: 73% (95%CI 51-100) vs. 100%; p < 0.001) and 12-month OS: 46% (95%CI 24-87) vs. 78% (95%CI 55-100; p = 0.19). Validation using age adjusted Cox regression analysis confirmed a decrease in the risk of progression or death with increasing α-diversity. PFS hazard ratio (HR) was 0.2 (95% CI: 0.1–0.5; p < 0.01) and OS HR was 0.3 (95% CI: 0.1–0.7; p < 0.01). Conclusions: Baseline high alpha-diversity in the gut microbiome is significantly associated with improved PFS and trended towards improved OS in pediatric patients with DMG in cohort 2 of PNOC022. Age-adjusted survival models reinforced its prognostic value for PFS and OS. These findings highlight the potential impact the gut microbiome has on outcomes and will be explored further and warrant our ongoing investigation in PNOC022.

Impact of gut microbiota (GM) and antibiotic (ATB) use on immunotherapy efficacy in patients with lung cancer (LC): Preliminary results from a prospective trial.

e20610 Background: LC is the leading cause of cancer death globally. Immune checkpoint inhibitors (ICI) have changed cancer treatment, but surpass resistance is still a challenge. The GM impact cancer immune-surveillance, and it can be modulated through diet/lifestyle and comedications (such as ATB). Microbiota-based biomarkers and interventions are promising strategies to overcome ICI resistance. We conducted a prospective trial (NCT04965129) to evaluate the impact of GM and ATB in non-small cell LC (NSCLC) patients (pts) treated with ICI. Methods: Pts with NSCLC eligible for ICI were assessed by monthly pharmaceutical visits and weekly telemonitoring to record the use of comedications up to 3 months before ICI start (T0) and from T0 to 4 months post-ICI start (T4), interaction assessment and pharmacotherapeutic follow-up. GM was analyzed at T0 and T4 by 16S rRNA sequencing. Alpha diversity was assessed using Shannon, Simpson, and InvSimpson indices; beta diversity by Bray-Curtis dissimilarity and differential relative frequency analysis using the Mann-Whitney test. Treatment response was evaluated according to RECIST v1.0, considering disease control (DC) if complete response, partial response, or stable disease. Results: We included 27 pts from February 2022 to February 2024: mean age of 70,6 years ± 7,5 [SD], mostly male (59%), with two or more comorbidities (63%), and polypharmacy (74%). Overall, 37% required pharmaceutical interventions and 47% used ATB. Progressive disease (PD) occurred in 88% of ATB users versus 12% of ATB non-users. ATB users and non-users did not differ in alpha or beta diversity. Clostridium difficile was detected in 75% of ATB users versus 0% non-ATB users. The relative frequency analysis brought up 8 species that significantly changed (p<0.05) between T0 and T4 among ATB users, including the pro- inflammatory Bacteroides clarus and Prevotella spp. Inversely, ATB non-users lost oral taxa Streptococcus spp. and gained the health-related Alistipes finegoldii . 81 species differed significantly between PD and DC (p<0.05) pts. All DC pts were positive for Akkermansia muciniphila versus 33% in PD pts, and they were enriched with health-related Lachnospiraceae (Roseburia spp., Blautia spp.) and Alistipes spp. Bacteroides caccae (p=0.035) and Prevotella copri (p=0.045) were present at TO and T4 in all patients. Conclusions: ATB use is associated to PD and pro-inflammatory taxa. Our study is a pioneer in the evaluation of Brazilian pts with LC treated with ICI. We contribute to equity and diversity in GM research towards more robust biomarkers for precision medicine. Clinical trial information: NCT04965129 .

The impact of mechanical unloading on the gut microbiota and the mitigating role of butyrate in bone loss.

The impact of mechanical unloading on the gut microbiota and the mitigating role of butyrate in bone loss.