Analysis Of Gut Microbiome Research Articles

Prospective evaluation of the breast microbiome and tumor microenvironment-related biomarkers of response to neoadjuvant systemic therapy in triple negative breast cancer.

TPS615 Background: Predictive biomarkers of response to combination chemotherapy and immune-checkpoint inhibitors are urgently needed to tailor treatment recommendations for patients with early-stage triple negative breast cancer (eTNBC). Our group has demonstrated that tumour-associated microbiota in primary breast tumours represent promising and novel candidate biomarkers for patients with breast cancer. We aim to prospectively interrogate the breast cancer microbiome and tumour microenvironment (TME) of eTNBC treated with neoadjuvant chemo-immunotherapy, and correlate with clinical outcome. Methods: Trial design: This prospective translational biomarker study is enrolling patients with eTNBC suitable for standard neoadjuvant systemic therapy followed by definitive surgery. The primary objective is to evaluate the change in breast cancer microbiome composition pre- and post-therapy. Secondary objectives include correlation of the breast microbiome with pathologic complete response (pCR) and survival outcomes, tumor infiltrating lymphocytes (TILs), PDL-1 and immune subset analysis, extracellular vesicles analysis and analysis of gut microbiome. Tumor tissue samples will be collected at baseline (mandatory research biopsy) and at the time of surgery. Microbiome evaluation will be conducted using metagenomic sequencing to assess changes in the relative abundance of microbial taxa. Blood and stool samples will be collected and analysed at baseline, on-treatment, at the time of surgery and post-operatively for secondary endpoints. Statistical analysis: Hierarchical clustering of samples based on relative abundance of the operational taxonomic units (OTUs) with sample composition at family and genus level will be performed. Alpha Diversity (Shannon Diversity Index) and Beta Diversity (Jaccard Similarity Index) will be analysed. Principal component analysis (PCA) and Random Forest analysis will be performed for classification and clustering analysis. Comparison of taxa or functions between clinical cohorts will be performed (two tailed Z test) and corrected using the false discovery rate to determine Q-values. Thirty patients will be recruited over 18-24 months. Current status: This University College Cork sponsored trial received ethics approval from the CREC in January 2024 and recruitment is ongoing. Those interested can contact uccctg@ucc.ie. This trial will provide a deeper insight into the potential role of the local breast microbiome as a predictive biomarker for response to neoadjuvant therapy in patients with eTNBC. The results will guide further studies exploring optimal immunomodulatory combinations for the treatment of TNBC and may provide evidence regarding future therapeutic targeting of the breast cancer microbiome.

Effect of dietary supplementation with sanguinarine on meat quality and lipid metabolism of broilers

Dietary Macleaya cordata extract (MCE) can improve the meat quality of poultry. However, the specific mechanism by which MCE regulates the meat quality has not been clarified yet. Sanguinarine (SAN) is one of the important natural active components in MCE. Our study aims to explore the regulatory mechanism of dietary SAN supplementation on meat quality through transcriptomic and gut microbiome analysis, thereby providing a basis for regularing meat quality with MCE. 240 1-day-old broilers were divided into 4 groups according to different doses of SAN (0, 0.225, 0.75, and 2.25 mg/kg). The results indicated that SAN significantly improve the physicochemical quality indicators of breast and thigh muscle in broilers, improved the serum biochemical indexes. Through transcriptome sequencing analysis of the liver and ileum tissues of broilers, we found that the differentially expressed genes induced by SAN were mainly enriched in lipid metabolism, which were related to the peroxisome proliferator-activated receptor (PPAR) pathway. It reconfirmed that SAN can regulate lipid metabolism in the body by promoting the expression of genes related to cholesterol metabolism, fatty acid transport and oxidation by RT-PCR, this ultimately affects the physicochemical quality of muscle. Additionally, through 16S rRNA sequencing analysis, we found that dietary addition of SAN increased the relative abundance of Bacteroides, Lactobacillus and unclassified_f_Lachnospiraceae, while decreased the relative abundance of Alistipes in ceca. To further investigate the impact of gut microbiota on lipid metabolism, we conducted a correlation analysis of PPAR pathway factor expression in cecum tissue and microflora structure. The results showed that Bacteroides exhibited a positive correlation with the expression of most genes in the PPAR signaling pathway. Unclassified_f__Lachnospiraceae is positively correlated with PPARγ, Cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and Acyl-CoA synthetase long-chain family member 5 (ACSL5). In conclusion, dietary addition of SAN can promote the genes expression of the PPAR pathway, target the regulation of intestinal microflora structure and abundance and regulate lipid metabolism, thereby improving meat quality of broilers.

Dietary sugar kelp consumption inhibits adipose tissue inflammation and fibrosis in male mouse model of diet-induced obesity

We previously demonstrated that consumption of U.S.-grown sugar kelp (Saccharina latissima) prohibits inflammation and fibrosis in the liver and white adipose tissue in male diet-induced obesity (DIO) mice. This study investigated whether sugar kelp can elicit similar benefits in female DIO mice. Male and female C57BL/6J mice were fed a low-fat (LF) control, a high-fat/high-sucrose/high-cholesterol (HF) control, or HF containing 6% sugar kelp (HF-Kelp) for 16 weeks. Body weight gain, serum triglyceride and total lipids, and glucose intolerance were decreased in male HF-Kelp compared with HF control. Furthermore, sugar kelp decreased gonadal white adipose tissue (gWAT) weight with smaller adipocytes and total body fat in males. In gWAT, male HF-Kelp exhibited less inflammation and fibrosis than the HF control, confirmed by histological analysis. Moreover, HF-Kelp increased physical activity only in males. Gut microbiome analysis showed sugar kelp elevated observed species and altered beta diversity in both males and females, suggesting changes in the gut microbiome may contribute to the effects of sugar kelp on gWAT inflammation and fibrosis. Therefore, our results demonstrate that sugar kelp consumption prevents obesity-induced inflammation and fibrosis in WAT in male mice, which is attributed, at least in part, to modest increases in metabolic rates, energy expenditure, and physical activity, and also modulating the gut microbiota.

Quorum-Sensing Signal DSF Inhibits the Proliferation of Intestinal Pathogenic Bacteria and Alleviates Inflammatory Response to Suppress DSS-Induced Colitis in Zebrafish.

The imbalance of gut microbiota is an important factor leading to inflammatory bowel disease (IBD). Diffusible signal factor (DSF) is a novel quorum-sensing signal that regulates bacterial growth, metabolism, pathogenicity, and host immune response. This study aimed to explore the therapeutic effect and underlying mechanisms of DSF in a zebrafish colitis model induced by sodium dextran sulfate (DSS). The results showed that intake of DSF can significantly improve intestinal symptoms in the zebrafish colitis model, including ameliorating the shortening of the intestine, reducing the increase in the goblet cell number, and restoring intestinal pathological damage. DSF inhibited the upregulation of inflammation-related genes and promoted the expression of claudin1 and occludin1 to protect the tightness of intestinal tissue. The gut microbiome analysis demonstrated that DSF treatment helped the gut microbiota of the zebrafish colitis model recover to normal at the phylum and genus levels, especially in terms of pathogenic bacteria; DSF treatment downregulated the relative abundance of Aeromonas hydrophila and Staphylococcus aureus, and it was confirmed in microbiological experiments that DSF could effectively inhibit the colonization and infection of these two pathogens in the intestine. This study suggests that DSF can alleviate colitis by inhibiting the proliferation of intestinal pathogens and inflammatory responses in the intestine. Therefore, DSF has the potential to become a dietary supplement that assists in the antibiotic and nutritional treatment of IBD.

Evaluation of fecal sample collection methods for feline gut microbiome profiling: fecal loop vs. litter box.

Microbial population structures within fecal samples are vital for disease screening, diagnosis, and gut microbiome research. The two primary methods for collecting feline fecal samples are: (1) using a fecal loop, which retrieves a rectal sample using a small, looped instrument, and (2) using the litter box, which collects stool directly from the litter. Each method has its own advantages and disadvantages and is suitable for different research objectives. Whole-genome shotgun metagenomic sequencing were performed on the gut microbiomes of fecal samples collected using these two methods from 10 adult cats housed in the same research facility. We evaluated the influence of collection methods on feline microbiome analysis, particularly their impact on DNA extraction, metagenomic sequencing yield, microbial composition, and diversity in subsequent gut microbiome analyses. Interestingly, fecal sample collection using a fecal loop resulted in a lower yield of microbial DNA compared to the litterbox method (p = 0.004). However, there were no significant differences between the two groups in the proportion of host contamination (p = 0.106), virus contamination (p = 0.232), relative taxonomy abundance of top five phyla (Padj > 0.638), or the number of microbial genes covered (p = 0.770). Furthermore, no significant differences were observed in alpha-diversity, beta-diversity, the number of taxa identified at each taxonomic level, and the relative abundance of taxonomic units. These two sample collection methods do not affect microbial population structures within fecal samples and collecting fecal samples directly from the litterbox within 6 hours after defecation can be considered a reliable approach for microbiome research.

Influences of Ruminococcus bromii and Peptostreptococcaceae on voluntary exercise behavior in a rodent model

IntroductionThis study investigates the relationship between the gut microbiome and voluntary exercise, focusing on wheel running activity in a rat model. The gut microbiome plays a crucial role in host physiology, homeostasis, and behavior. Alterations in the gut microbiome have been linked to various pathological states and health conditions, including obesity.MethodsGiven the strong association between physical inactivity and obesity development, our study aimed to identify microbiome factors associated with elevated levels of voluntary exercise. Male Sprague Dawley rats were used in the 4-week exercise paradigm in which voluntary wheel running behavior was monitored alongside weekly microbiome sampling from fecal pellets.ResultsWe observed individual differences in running activity among the cohort. Significant positive correlations in running distance were identified across the 4-week time course, suggesting that running activity ranking was largely preserved. Furthermore, earlier running activity emerged as a potential predictor for subsequent running behaviors. Analysis of gut microbiome revealed that alpha diversity was positively correlated with daily running distances, with significant differences in beta diversity observed between high and low running groups. Taxonomic analysis showed distinct abundance differences between running and sedentary conditions, particularly in the Ruminococcaceae and Peptostreptococcaceae families.DiscussionOur results suggest that the microbiome composition changes significantly early in exercise exposure, potentially influencing exercise behavior. Ruminococcaceae, particularly R. bromii, was identified as a significant contributor to exercise adaptation, while Peptostreptococcaceae was inversely related to running performance as well as alpha diversity. This study underscores the potential of the gut microbiome as a modulator of exercise behavior. Future research should focus on the biological mechanisms linking microbiome changes to exercise adaptation, with R. bromii and Peptostreptococcus as promising candidates for influencing exercise behaviors through future interventional studies.

Comparative analysis of gut microbiome of mangrove brachyuran crabs revealed patterns of phylosymbiosis and codiversification.

The acquisition of microbial symbionts enables animals to rapidly adapt to and exploit novel ecological niches, thus significantly enhancing the evolutionary fitness and success of their hosts. However, the dynamics of host-microbe interactions and their evolutionary implications remain largely underexplored in marine invertebrates. Crabs of the family Sesarmidae (Crustacea: Brachyura) are dominant inhabitants of mangrove forests and are considered keystone species there. Their rapid diversification, particularly after adopting a plant-feeding lifestyle, is believed to have been facilitated by symbiotic gut microbes, enabling successful colonization of intertidal and terrestrial environments. To investigate the patterns and mechanisms shaping the microbial communities and the role of microbes in the evolution of Sesarmidae, we characterized and compared the gut microbiome compositions across 43 crab species from Sesarmidae and other mangrove-associated families using 16S metabarcoding. We found that the gut microbiome assemblages in crabs are primarily determined by host identity, with a secondary influence from environmental factors such as microhabitat and sampling location, and to a lesser extent influenced by biological factors such as sex and gut region. While patterns of phylosymbiosis (i.e. when microbial community relationships recapitulate the phylogeny of their hosts) were consistently observed in all beta-diversity metrics analysed, the strength of phylosymbiosis varied across crab families. This suggests that the bacterial assemblages in each family were differentially shaped by different degrees of host filtering and/or other evolutionary processes. Notably, Sesarmidae displayed signals of cophylogeny with its core gut bacterial genera, which likely play crucial functional roles in their hosts by providing lignocellulolytic enzymes, essential amino acids, and fatty acids supplementation. Our results support the hypothesis of microbial contribution to herbivory and terrestrialization in mangrove crabs, highlighting the tight association and codiversification of the crab holobiont.

The efficacy and safety of MARS-PD: Meridian activation remedy system for Parkinson's disease-A single-center, assessor and statistician-blinded, parallel-group randomized, controlled trial protocol.

Parkinson's disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD. In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson's Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture. Previous studies by the authors have indicated MARS-PD's safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD. cris.nih.go.kr KCT0006646 -First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 -First posted on 11 November 2022.

Abstract PO4-03-04: Characterization of Gut Microbiome of patients with early-stage breast cancer treated with neoadjuvant chemotherapy

Abstract Objective: The gut microbiome (GM) has been identified as one of the major environmental factors that can regulate the development and maintenance of the immune system. In oncology, while the importance of GM has been evaluated in more immunogenic tumors such as melanoma, lung carcinoma and clear cell carcinoma, its importance in early-stage breast cancer (eBC) is underexplored. The aim of this study was to characterize the GM of patients with eBC who underwent neoadjuvant chemotherapy (NACT) and to evaluate its association with clinicopathologic prognostic factors and outcomes. Methods: This was a prospective study conducted at two Brazilian institutions. Fecal samples were collected at baseline (time 1) and prior to surgery (time 2) from 55 patients who received NACT with anthracycline/taxane. Gut microbiome was analyzed by 16S rRNA amplicon sequencing to characterize the α (InvSimpson index) and β (weighted UniFrac distance metric) diversity, as well as taxonomic composition. Clinicopathologic prognostic factors were retrieved from medical records. Pathological complete response (pCR) was defined as the absence of invasive carcinoma in breast and axillary nodes (ypT0/Tis ypN0). Stromal tumor-infiltrating lymphocytes (sTIL) were reported according to the TIL working group criteria. Information about prior use (< 60 days before stating on NACT) of antibiotic (ATB) was obtained directly from patients. Statistical significance was set at P ≤ 0.05 and analysis of composition of microbiomes (ANCOM-BC2) was used to identify enriched genera with p-values adjusted using FDR correction ≤ 0.25. Results: Median age was 49 years (range 31-73). Eleven patients (20%) reported prior antibiotic use at baseline. About 34.5% of patients had HR+/HER2- tumors, 45.4% had triple negative breast cancer (TNBC), and 20% had HER2-positive breast cancer. Fourteen (25%) patients achieved a pCR. Out of 55, 47 (85.4%) had sTIL information. There was no significant difference in alpha diversity (p = 0.6) or beta-diversity (p = 0.8) between the pCR and residual disease group nor within clinical pathologic factors (age, staging, histological tumor grade, subtype of breast cancer based on IHC, sTIL). The most abundant taxon in both time 1 and time 2 were the same (Blautia at genus level, Lachnospiraceae at family level, and Lachnospirales at order level), and longitudinal samples collected during NACT showed no significant changes in GM composition. At baseline, we found an enrichment for Clostridia sp. among patients who did not use ATB (p < 0.05, pFDR ≤ 0.25). Additionally, we found enrichment for Bifidobacterium (p < 0.05, pFDR ≤ 0.25) among patients with HER2 subtype who presented residual disease. Conclusions: Gut microbiome analysis in early breast cancer is feasible and to our knowledge, this is the first study to evaluate the intestinal microbiota of Brazilian patients with breast cancer. We did not observe any significant association between GM diversity and taxonomic composition with clinical pathologic factors and pCR in this study, nor did we observe changes in the ecological balance of the GM following NACT in breast cancer. Further studies are needed to explore the potential influence of the gut microbial ecosystem on tumor biology and response to neoadjuvant chemo-immunotherapy. Citation Format: Ludmila Thommen, Vitor Heidrich, Rosângela Vieira de Andrade, Luiza Nardin Weis, Maria Sueli Soares Felipe, Melissa Lole Da Cas Vita, Thiago David Alves Pinto, Anamaria Camargo, Romualdo Barroso-Sousa. Characterization of Gut Microbiome of patients with early-stage breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-04.

Cannabidiol (CBD) facilitates cocaine extinction and ameliorates cocaine-induced changes to the gut microbiome in male C57BL/6JArc mice

Cocaine use disorder (CUD) is a global health problem with no approved medications. One potential treatment target is the gut microbiome, but it is unknown if cocaine induces long-lasting effects on gut microbes. A novel therapeutic candidate for CUD, cannabidiol (CBD), can improve gut function in rodent models. It is possible that protective effects of CBD against cocaine use are mediated by improving gut health. We examined this question in this experiment. Cocaine conditioned place preference (CPP) was conducted in adult male C57BL/6JArc mice. Mice were treated with vehicle or 20 mg/kg CBD prior to all cocaine CPP sessions (N = 11–13/group). Mice were tested drug free 1, 14 and 28 days after cessation of cocaine and CBD treatment. Fecal samples were collected prior to drug treatment and after each test session. Gut microbiome analyses were conducted using 16 s rRNA sequencing and correlated with behavioural parameters. We found a persistent preference for a cocaine-environment in mice, and long-lasting changes to gut microbe alpha diversity. Cocaine caused persistent changes to beta diversity which lasted for 4 weeks. CBD treatment reduced cocaine-environment preference during abstinence from cocaine and returned gut beta diversity measures to control levels. CBD treatment increased the relative abundance of Firmicutes phyla and Oscillospira genus, but decreased Bacteroidetes phyla and Bacteroides acidifaciens species. Preference score in cocaine-treated mice was positively correlated with abundance of Actinobacteria, whereas in mice treated with CBD and cocaine, the preference score was negatively correlated with Tenericutes abundance. Here we show that CBD facilitates cocaine extinction memory and reverses persistent cocaine-induced changes to gut microbe diversity. Furthermore, CBD increases the abundance of gut microbes which have anti-inflammatory properties. This suggests that CBD may act via the gut to reduce the memory of cocaine reward. Our data suggest that improving gut health and using CBD could limit cocaine abuse.

Integrated analysis of gut metabolome, microbiome, and exfoliome data in an equine model of intestinal injury

BackgroundThe equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-steroidal anti-inflammatory drug (NSAID)-induced intestinal inflammation and (2) apply computational data integration methods to examine host-microbiota interactions.MethodsTwenty horses were randomly assigned to 1 of 2 groups (n = 10): control (placebo paste) or NSAID (phenylbutazone 4.4 mg/kg orally once daily for 9 days). Fecal samples were collected on days 0 and 10 and analyzed with respect to microbiota (16S rDNA gene sequencing), metabolomic (untargeted metabolites), and host exfoliated cell transcriptomic (exfoliome) changes. Data were analyzed and integrated using a variety of computational techniques, and underlying regulatory mechanisms were inferred from features that were commonly identified by all computational approaches.ResultsPhenylbutazone induced alterations in the microbiota, metabolome, and host transcriptome. Data integration identified correlation of specific bacterial genera with expression of several genes and metabolites that were linked to oxidative stress. Concomitant microbiota and metabolite changes resulted in the initiation of endoplasmic reticulum stress and unfolded protein response within the intestinal mucosa.ConclusionsResults of integrative analysis identified an important role for oxidative stress, and subsequent cell signaling responses, in a large animal model of GI inflammation. The computational approaches for combining non-invasive platforms for unbiased assessment of host GI responses (e.g., exfoliomics) with metabolomic and microbiota changes have broad application for the field of gastroenterology.8RW7XWUKiyvANo7PaYZA3nVideo

Gut bacteriome and mood disorders in women with PCOS.

How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31years and age 46years, and stool samples were collected from the women at age 46years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. N/A.

Conjugated Linoleic Acid Ameliorates High Fat-Induced Insulin Resistance via Regulating Gut Microbiota-Host Metabolic and Immunomodulatory Interactions.

Interaction between gut microbiota, host immunity and metabolism has been suggested to crucially affect the development of insulin resistance (IR). This study aims to investigate how gut microbiota, inflammatory responses and metabolism in individuals with IR are affected by the supplementation of conjugated linoleic acid (CLA) and how this subsequently affects the pathophysiology of IR by using a high-fat diet-induced IR mouse model. Serum biochemical indices showed that 400 mg/kg body weight of CLA effectively attenuated hyperglycemia, hyperlipidemia, glucose intolerance and IR, while also promoting antioxidant capacities. Histomorphology, gene and protein expression analysis revealed that CLA reduced fat deposition and inflammation, and enhanced fatty acid oxidation, insulin signaling and glucose transport in adipose tissue or liver. Hepatic transcriptome analysis confirmed that CLA inhibited inflammatory signaling pathways and promoted insulin, PI3K-Akt and AMPK signaling pathways, as well as linoleic acid, arachidonic acid, arginine and proline metabolism. Gut microbiome analysis further revealed that these effects were highly associated with the enriched bacteria that showed positive correlation with the production of short-chain fatty acids (SCFAs), as well as the improved SCFAs production simultaneously. This study highlights the therapeutic actions of CLA on ameliorating IR via regulating microbiota-host metabolic and immunomodulatory interactions, which have important implications for IR control.

Hovenia dulcis Fruit Peduncle Polysaccharides Reduce Intestinal Dysbiosis and Hepatic Fatty Acid Metabolism Disorders in Alcohol-Exposed Mice.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) have the potential to alleviate alcoholic liver injury and play essential roles in treating alcohol-exposed liver disease; however, the hepatoprotective effects and mechanisms remain elusive. In this study, we investigated the hepatoprotective effects of HDPs and their potential mechanisms in alcohol-exposed mice through liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels, and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. When applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria, significant increases in Firmicutes at the phylum level, increased Lactobacillus abundance, and decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid and glycerophospholipid metabolism, and identified two important metabolites-C00157 (phosphatidylcholine, a glycerophospholipid plays a central role in energy production) and C04230 (1-Acyl-sn-glycero-3-phosphocholine, a lysophospholipid involved in the breakdown of phospholipids)-involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs have a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity

BackgroundObesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment.ResultsAfter 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups.Conclusions1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.

Comparative Analysis of Gut Microbiomes in Laboratory Chinchillas, Ferrets, and Marmots: Implications for Pathogen Infection Research.

Gut microbes play a vital role in the health and disease of animals, especially in relation to pathogen infections. Chinchillas, ferrets, and marmots are commonly used as important laboratory animals for infectious disease research. Here, we studied the bacterial and fungal microbiota and discovered that chinchillas had higher alpha diversity and a higher abundance of bacteria compared to marmots and ferrets by using the metabarcoding of 16S rRNA genes and ITS2, coupled with co-occurrence network analysis. The dominant microbes varied significantly among the three animal species, particularly in the gut mycobiota. In the ferrets, the feces were dominated by yeast such as Rhodotorula and Kurtzmaniella, while in the chinchillas, we found Teunomyces and Penicillium dominating, and Acaulium, Piromyces, and Kernia in the marmots. Nevertheless, the dominant bacterial genera shared some similarities, such as Clostridium and Pseudomonas across the three animal species. However, there were significant differences observed, such as Vagococcus and Ignatzschineria in the ferrets, Acinetobacter and Bacteroides in the chinchillas, and Bacteroides and Cellvibrio in the marmots. Additionally, our differential analysis revealed significant differences in classification levels among the three different animal species, as well as variations in feeding habitats that resulted in distinct contributions from the host microbiome. Therefore, our data are valuable for monitoring and evaluating the impacts of the microbiome, as well as considering potential applications.

Abstract 121: Gut microbiome association with dietary habits and abemaciclib-induced diarrhea:A multicenter, prospective study

Abstract Background: Abemaciclib, a leading treatment used for HR-positive, HER2-negative metastatic and primary breast cancer patients, often causes diarrhea. Understanding the reasons machinery behind this adverse event leads to reduce the toxicity and improve the quality of life. This study explores a hypothesis that specific gut microbiota profiles are engaged in gastrointestinal toxicities caused by abemaciclib and may be influenced by patients' dietary habits. We assessed it using the Brief Diet History Questionnaire (BDHQ). Materials and Methods: Our research involved collecting blood and stool samples, as well as dietary data through the BDHQ from 39 patients diagnosed with HR-positive, HER2-negative metastatic breast cancer. These were obtained prior to the start of abemaciclib treatment, at the first imaging evaluation, and at either disease progression or treatment discontinuation due to adverse effects. Incidence and severity of diarrhea were evaluated by the Bristol stool scale at baseline, from day 1 to day 14, and at day 90 of treatment. Stool samples were collected at baseline and at day 90 after the start of abemaciclib treatment. We conducted 16S metagenomic sequencing for gut microbiome analysis and used mass cytometry along with RNA-sequencing to profile immune cells. Results: Our findings indicate a significant association between the gut microbiota composition and abemaciclib-induced diarrhea, which also appears to be modulated by dietary patterns. An increase in Dorea was observed with higher Bristol Stool Scale scores, while Bifidobacterium and Sellimonas abundances were inversely related to changes in stool characteristics. The presence of Dorea was also positively associated with the consumption of specific food items such as tea, root vegetables, and dietary minerals. In contrast, Collinsella abundance decreased as the frequency of diarrhea increased and it was associated with the consumption of fried foods and certain fats. Conclusion: The prevalence of diarrhea as a side effect of abemaciclib treatment highlights the need for better management strategies. Our study indicates that gut microbiota, altered by dietary habits, is linked to this adverse effect. The data suggest a possibility of using specific gut bacteria as probiotics to alleviate this condition, pointing towards personalized dietary interventions as a potential avenue for improving treatment tolerance. Citation Format: Yuri Fujimoto, Kosuke Kawaguchi, Yurina Maeshima, Hiroshi Ishiguro, Kazuhiko Yamagami, Sachiko Takahara, Hirofumi Suwa, Masae Torii, Shigenori Nagai, Yasuaki Sagara, Wakako Tsuji, Hiroyasu Yamashiro, Takeshi Kotake, Shinji Fukuda, Kuniaki Saito, Yasuko Yamamoto, Masako Kataoka, Yuki Himoto, Atsushi Yonezawa, Yukiko Fukui, Yuki Nakamura, Wei Li, Sunao Tanaka, Masahiro Takada, Satoshi Morita, Masakazu Toi. Gut microbiome association with dietary habits and abemaciclib-induced diarrhea:A multicenter, prospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 121.

Comparative analysis of gut microbiome in Pangasionodon hypopthalmus and Labeo catla during health and disease.

The present study was conducted to study the composition of gut microbiome in the advanced fingerling and fingerling stage of striped pangasius catfish and catla during healthy and diseased conditions. Healthy pangasius and catla fishes were obtained from commercial farms and injected with the LD50 dose of A. hydrophila. The intestinal samples from the control and injected group were collected and pooled for 16s metagenomic analysis. Community analysis was performed by targeting the 16s rRNA gene to explore and compare the gut microbiota composition of these fishes. The operational taxonomic units (OTUs) consisted of four major phyla: Bacteroidia, Proteobacteria, Firmicutes, and Actinobacteria. Alpha and beta diversity indices were carried out to understand the diversity of microbes within and between a sample. While comparing the advanced fingerling and fingerling stage gut microbiome of Pangasius catfish, the dominance of Proteobacteria was found in fingerlings, whereas Firmicutes and Bacteroides were found in advanced fingerlings. In catla, Proteobacteria and Bacteroides were predominant. Taxonomic abundance of the microbiota in control and diseased Pangasius and catla fishes at phylum, class, order, family, genus, and species levels were also depicted. The present study is the first of its kind, and it will help to identify the diversity of novel potential bacterial species involved in disease protection of fishes. It can lead to the development of sustainable prophylactic measures against (re-)emerging bacterial diseases in aquaculture.

Metagenomic gut microbiome analysis of Japanese patients with multiple chemical sensitivity/idiopathic environmental intolerance

BackgroundAlthough the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples.MethodsWe prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC).ResultsWe observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively).ConclusionsThe gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS.Trial registrationThis study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018.

Effects of dietary arsenic exposure on liver metabolism in mice

Arsenic, a ubiquitous environmental toxicant with various forms and complex food matrix interactions, can reportedly exert differential effects on the liver compared to drinking water exposure. To examine its specific liver-related harms, we targeted the liver in C57BL/6 J mice (n=48, 8-week-old) fed with arsenic-contaminated food (30 mg/kg) for 60 days, mimicking the rice arsenic composition observed in real-world scenarios (iAsV: 7.3%, iAsIII: 72.7%, MMA: 1.0%, DMA: 19.0%). We then comprehensively evaluated liver histopathology, metabolic changes, and the potential role of the gut-liver axis using human hepatocellular carcinoma cells (HepG2) and microbiota/metabolite analyses. Rice arsenic exposure significantly altered hepatic lipid (fatty acids, glycerol lipids, phospholipids, sphingolipids) and metabolite (glutathione, thioneine, spermidine, inosine, indole-derivatives, etc.) profiles, disrupting 33 metabolic pathways (bile secretion, unsaturated fatty acid biosynthesis, glutathione metabolism, ferroptosis, etc.). Pathological examination revealed liver cell necrosis/apoptosis, further confirmed by ferroptosis induction in HepG2 cells. Gut microbiome analysis showed enrichment of pathogenic bacteria linked to liver diseases and depletion of beneficial strains. Fecal primary and secondary bile acids, short-chain fatty acids, and branched-chain amino acids were also elevated. Importantly, mediation analysis revealed significant correlations between gut microbiota, fecal metabolites, and liver metabolic alterations, suggesting fecal metabolites may mediate the impact of gut microbiota and liver metabolic disorders. Gut microbiota and its metabolites may play significant roles in arsenic-induced gut-liver injuries. Overall, our findings demonstrate that rice arsenic exposure triggers oxidative stress, disrupts liver metabolism, and induces ferroptosis.