Gut Microbial Composition Research Articles

Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum

BackgroundGut microbiota dysbiosis is linked to Alzheimer’s disease (AD), but our understanding of the molecular and neuropathological bases underlying such association remains fragmentary.MethodsUsing 16S rDNA amplicon sequencing, untargeted metabolomics, and multi-modal magnetic resonance imaging, we examined group differences in gut microbiome, fecal metabolome, neuroimaging measures, and cognitive variables across 30 patients with AD, 75 individuals with mild cognitive impairment (MCI), and 61 healthy controls (HC). Furthermore, we assessed the associations between these multi-omics changes using correlation and mediation analyses.ResultsThere were significant group differences in gut microbial composition, which were driven by 8 microbial taxa (e.g., Staphylococcus and Bacillus) exhibiting a progressive increase in relative abundance from HC to MCI to AD, and 2 taxa (e.g., Anaerostipes) showing a gradual decrease. 26 fecal metabolites (e.g., Arachidonic, Adrenic, and Lithocholic acids) exhibited a progressive increase from HC to MCI to AD. We also observed progressive gray matter atrophy in broadly distributed gray matter regions and gradual micro-structural integrity damage in widespread white matter tracts along the AD continuum. Integration of these multi-omics changes revealed significant associations between microbiota, metabolites, neuroimaging, and cognition. More importantly, we identified two potential mediation pathways: (1) microbiota → metabolites → neuroimaging → cognition, and (2) microbiota → metabolites → cognition.ConclusionAside from elucidating the underlying mechanism whereby gut microbiota dysbiosis is linked to AD, our findings may contribute to groundwork for future interventions targeting the microbiota-metabolites-brain-cognition pathways as a therapeutic strategy in the AD continuum.

Alpha synuclein overexpression can drive microbiome dysbiosis in mice

Growing evidence indicates that persons with Parkinson disease (PD), have a unique composition of indigenous gut microbes. Given the long prodromal or pre-diagnosed period, longitudinal studies of the human and rodent gut microbiome before symptomatic onset and for the duration of the disease are currently lacking. PD is partially characterized by the accumulation of the protein α-synuclein (α-syn) into insoluble aggregates, in both the central and enteric nervous systems. As such, several experimental rodent and non-human primate models of α-syn overexpression recapitulate some of the hallmark pathophysiologies of PD. These animal models provide an opportunity to assess how the gut microbiome changes with age under disease-relevant conditions. Here, we used a transgenic mouse strain, which overexpress wild-type human α-syn to test how the gut microbiome composition responds in this model of PD pathology during aging. Using shotgun metagenomics, we find significant, age and genotype-dependent bacterial taxa whose abundance becomes altered with age. We reveal that α-syn overexpression can drive alterations to the gut microbiome composition and suggest that it limits diversity through age. Taxa that were most affected by genotype-age interaction were Lactobacillus and Bifidobacteria. In a mouse model, we showed direct link between alpha synuclein geneotype (hallmark of PD), a dysbiotic and low-diversity gut microbiome, and dysbiotic levels of Bifidobacteria and Lactobacillus (most robust features of PD microbiome). Given emerging data on the potential contributions of the gut microbiome to PD pathologies, our data provide an experimental foundation to understand how the PD-associated microbiome may arise as a trigger or co-pathology to disease.

Gut microbiota of patients insusceptible to olanzapine-induced fatty liver disease relieves hepatic steatosis in rats.

Olanzapine-induced fatty liver disease continues to pose vital therapeutic challenges in the treatment of psychiatric disorders. In addition, we observed that some patients were less prone to hepatic steatosis induced by olanzapine. Therefore, we aimed to investigate the role and the underlying mechanism of the intestinal flora in olanzapine-mediated hepatic side effects and explore the possible countermeasures. Our results showed that patients with different susceptibilities to olanzapine-induced fatty liver disease had different gut microbial diversity and composition. Furthermore, we performed fecal microbiota treatment (FMT), and confirmed that the gut microbiome of patients less prone to the fatty liver caused by olanzapine exhibited an alleviation against fatty liver disease in rats. In terms of mechanism, we revealed that the cross talk of leptin with the gut-short-chain fatty acid (SCFA)-liver axis play a critical role in olanzapine-related fatty degeneration in liver. These findings propose a promising strategy for overcoming the issues associated with olanzapine application and will hopefully inspire future in-depth research of fecal microbiota-based therapy in olanzapine-induced fatty liver disease.NEW & NOTEWORTHY Patients who were less inclined to have olanzapine-induced fatty liver had different gut microbiota profiles than did those in the susceptible cohort. Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Butyricicoccaceae, and Christensenellaceae were enriched in patients who were less prone to fatty liver disease caused by olanzapine. Fecal microbiota treatment (FMT) with these fecal samples promoted short-chain fatty acid (SCFA) production, which attenuated the circulating leptin and inhibited FASN and ACC1, thereby suppressing lipid synthesis in the liver, ultimately leading to alleviation of hepatic steatosis.

A critical review on effects of artificial sweeteners on gut microbiota and gastrointestinal health.

Artificial sweeteners have emerged as popular alternatives to traditional sweeteners, driven by the growing concern over sugar consumption and its associated rise in obesity and metabolic disorders. Despite their widespread use, the safety and health implications of artificial sweeteners remain a topic of debate, with conflicting evidence contributing to uncertainty about their long-term effects. This review synthesizes current scientific evidence regarding the impact of artificial sweeteners on gut microbiota and gastrointestinal health. Our analysis of in vitro experiments, animal models, and clinical trials reveals that artificial sweeteners can alter the composition and abundance of gut microbes. These changes raise concerns about their potential to affect overall gut health and contribute to gastrointestinal disorders. Additionally, artificial sweeteners have been shown to influence the production of metabolites by gut bacteria, further impacting systemic health. The findings suggest that artificial sweeteners may have complex and sometimes contradictory effects on gut microbiota. While some studies indicate potential benefits, such as reduced caloric intake and weight management, others highlight detrimental effects on microbial balance and metabolic functions. The inconsistent results underscore the need for further research to comprehensively understand the physiological impacts of various artificial sweeteners on human health. Future studies should aim for long-term, well-controlled investigations to clarify these relationships, ensuring evidence-based guidelines for the safe use of artificial sweeteners in diet management. © 2025 Society of Chemical Industry.

Environmentally-Relevant Concentrations of Atrazine Had Minor Impacts on Gut Microbiota and Liver Metabolite in Juvenile Turtles.

Toxic effects of herbicide atrazine (ATR) have been evaluated in various aquatic organisms, but our understanding of its potential impacts in reptile species remains limited. In this study, the functional performances, and gut microbiota and liver metabolite alterations of ATR-exposed Mauremys sinensis juveniles were measured to evaluate its potential toxic effects in turtles. ATR exposure had no impact on the growth rate, but would allow turtles to right themselves more quickly. Despite having no difference in gut microbial diversity, the microbial composition was slightly changed after ATR exposure. For example, a few bacterial genera were shown to increase in exposed turtles (e.g., Turicibacter), or only observed in higher-concentration groups (e.g., Dialister, Alistipes, Delftia). Similarly, only a few identified liver metabolites were found to change significantly (e.g., decreased levels of arginine and N-acetylneuraminate; increased levels of glutathione and isomaltose in low-concentration exposure group) after ATR exposure. Overall, minor alterations in gut microbial composition and liver metabolite indicated that ATR exposure at environmentally-relevant concentrations only produced limited impacts in turtle species, although these alterations might have potentially adverse consequences on the long-term health of exposed turtles.

Chrysanthemum extract mitigates high-fat diet-induced inflammation, intestinal barrier damage and gut microbiota disorder.

An effective intervention for obesity without side effects is needed. Chrysanthemum may be the preferred choice due to its influence in the improvement of glycolipid metabolism. This study assessed the efficacy of chrysanthemum and its flavonoids in mitigating high-fat diet (HFD) induced obesity, focusing on the integrity of the intestinal barrier, inflammation, and gut microbiota. Fifty male C57BL/6J mice were divided into 5 groups randomly: normal control (NC), HFD, HFD with chrysanthemum aqueous extract (CM), HFD with a low-dose flavonoid extract of chrysanthemum (FLL), and HFD with a high-dose flavonoid extract of chrysanthemum (FLH). The results showed that after 9 weeks of intervention with CM, FLL and FLH, the body weight and blood lipid levels of mice were reduced. The chrysanthemum treatment regimens down-regulated the gene expression and protein levels of TLR4, MyD88, TRAF6 and NF-κB, upregulated the gene expression levels of ZO-1 and occludin, and decreased the levels of LPS and diamine oxidase (DAO) in the serum. With CM, FLL and FLH, the levels of the inflammatory factors IL-1β, TNF-α, and IL-6 were decreased, and the abundance of pernicious bacteria Lachnoclostridium, Streptococcus and Enterococcus was decreased. Notably, the purified chrysanthemum flavonoid extract showed greater effects as compared to the CM. The study demonstrated that chrysanthemum extracts could achieve anti-obesity effects by strengthening the intestinal barrier function, relieving inflammation and modulating the gut microbial composition.

Role of Crosstalk Between Gut Microbiota and Immune Cells in Colorectal Cancer: A Narrative Review

Abstract Colorectal cancer (CRC) ranks among the most prevalent and deadly cancers globally, with its incidence increasing due to lifestyle factors such as increased consumption of red meat and decreased vegetable intake. A distinctive aspect of CRC is its strong connection to the gut microbiota, which is crucial in both tumorigenesis and immune regulation. This narrative review provides a comprehensive analysis of the interactions between gut microbiota and the immune system, focusing on their importance in CRC progression and responses to immunotherapy. Imbalances in the composition of gut microbes are strongly associated with CRC development. Notably, species such as Fusobacterium nucleatum and Bacteroides fragilis have been identified as key regulators of immune responses within the tumor microenvironment. These microbes affect the functions of immune cells, such as T cells, macrophages and myeloid-derived suppressor cells, thereby influencing cancer progression and prognosis. Additionally, this review underscores the potential of gut microbiota as biomarkers for CRC detection and outcome prediction. There is also growing interest in the use of probiotics, fecal microbiota transplantation and dietary modifications as supplementary treatments. A deeper understanding of how microbial communities interact with the immune system may pave the way for novel personalized therapies, particularly by enhancing the effectiveness of immune checkpoint inhibitors.

P1344 Impaired health-related quality of life is associated with alterations in gut microbiota signatures in patients with Inflammatory Bowel Disease: baseline data from the Australian IBD Microbiome study

Abstract Background Inflammatory Bowel Disease (IBD) activity as well as disease monitoring and management have a substantial impact on the health-related quality of life (HRQoL) of affected patients1. This study investigated the association between HRQoL and gut microbial composition in IBD patients using the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). Methods Paired faecal and oral samples alongside participant demographics, disease characteristics and the IBDQ-32 survey were collected at baseline from patients with Crohn’s disease (CD) or ulcerative colitis (UC) enrolled in the Australian IBD Microbiome (AIM) study2 from June 2019 to November 2023. IBDQ-32 scores range from 32 to 224, with a higher score indicating better HRQoL. Patients were divided into two groups: impaired HRQoL (cumulative score <170) and preserved HRQoL (>170). Faecal and oral samples were self-collected in DNA stabilising buffer, aliquoted and stored at -80oC until extraction. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Chao1) between groups were assessed using Mann-Whitney U tests. Linear discriminant analysis was performed between groups to identify significantly enriched bacterial taxa. Beta diversity (weighted UniFrac dissimilarity) in bacterial communities were shown using Principal Coordinate Analysis (PCoA), and significance of variance was tested using ADONIS in R. Results 446 participants (232 CD, 214 UC) returned baseline faecal (n = 403) and/or oral samples (n = 436) and were included in the analysis, with patient and HRQoL characteristics in Table 1. Most CD and UC patients were in clinical remission at baseline (77.4% and 65.2% respectively, Table 1). Despite this, impaired HRQoL was common in both CD (42%) and UC (41%). Patients with impaired HRQoL had lower faecal microbial alpha and beta diversity (Fig 1A,B). There were no differences in alpha or beta diversity in oral samples. Linear discriminant analysis showed 9 and 36 significantly altered genera enrichment in impaired and preserved HRQoL faecal samples respectively (Fig 1C). Conclusion Despite a high proportion of clinical and biochemical remission, impaired HRQoL was common amongst UC and CD patients within the AIM study. Lower faecal but not oral alpha diversity was associated with impaired HRQoL, indicating reduced microbial richness in the gut. A high number of bacterial taxa had differential enrichment according to HRQoL status. Identification of a distinct microbial signature associated with impaired HRQoL may help to identify patients that require both optimisation of disease control and greater psychosocial support.

P1318 Temporal Changes of Gut Microbiota and Micro-RNAs according to Disease Activity in Chronic Colitis

Abstract Background Both gut microbiota and micro-RNAs (miRNAs) have been implicated in the pathogenesis of inflammatory bowel disease. We aimed to investigate the temporal changes and their interactions between gut microbiota and miRNAs according to the disease activity using multi-omics analysis in a murine chronic colitis model. Methods Chronic colitis was induced in the C57BL/6 mice by three rounds of 2.5% DSS exposure. Mice were divided into three groups (n= 8 per group): control group, active group (sacrified at 3 days after the third DSS), and recovery group (sacrificed at 80 days after the third DSS). Clinical activities including weight change and histologic findings of colonic segments were examined. DNA was extracted from mouse feces, and 16S rRNA gene sequencing was performed to evaluate changes in gut microbiota. miRNA expression levels were measured by microarray analysis from mouse colonic tissues. Correlation and network analyses were performed to evaluate the interactions between gut microbiota and miRNAs. Results Alpha diversity indices were increased in the active group compared to control and recovery group. PCoA of metagenomic sequencing showed that the gut microbial profile of the active group was distinctly different from the control group, while the gut microbial profile of the recovery group was similar to the control group. On the other hand, PCoA of miRNA microarray showed that the active group had a significantly different miRNA expression pattern compared to the control group, while the recovery group had a similar miRNA expression pattern to the active group. In taxonomic and miRNA analyses, 147 differential abundant bacterial ASVs and 30 differential expressed miRNAs were identified in the active group compared to the recovery group. Spearman correlation and network analysis between gut microbiota and miRNAs, which showed significant differences between the active and the recovery groups, revealed significant associations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p. Conclusion In the active phase of chronic colitis, the gut microbial composition and miRNA expression were significantly altered, while in the recovery phase of chronic colitis, the gut microbial profile was similar to that of control, but a significantly different miRNA expression pattern was observed. Specific miRNAs were associated with specific bacterial ASVs, suggesting the interactions between miRNAs and gut microbiota in the development of chronic colitis. Our data suggested significant correlations between the genera Akkermansia and Phocaeicola and miR-34c-3p, miR-483-5p, miR-200b-3P, and miR-378a-3p in the active phase of chronic colitis.

A legume-enriched diet improves metabolic health in prediabetes mediated through gut microbiome: a randomized controlled trial

Healthy dietary patterns rich in legumes can improve metabolic health, although their additional benefits in conjunction with calorie restriction have not been well-established. We investigated effects of a calorie-restricted, legume-enriched, multicomponent intervention diet compared with a calorie-restricted control diet in 127 Chinese prediabetes participants, living in Singapore. The study was a 16-week, single-blind, parallel-design, randomized controlled trial (n = 63 intervention group (IG), n = 64 control group (CG); mean ± SD age 62.2 ± 6.3 years, BMI 23.8 ± 2.6 kg/m2). Primary outcomes were markers of glycemia and all measurements were taken at 2 or 4-weekly intervals. At the end of 16 weeks, both groups had significantly lower BMI (q(Time) = 1.92 ×10-42, β = -0.02) compared with baseline, with minimal difference between groups. The IG had significantly greater reductions in LDL cholesterol (q(Treatment×Time) = 0.01, β = -0.16), total cholesterol (q(Treatment×Time) = 0.02, β = -0.3) and HbA1c (q(Treatment×Time) = 0.04, β = -0.004) compared with CG, alongside increases in fiber degrading species in IG, mediated through metabolites such as bile acids and amino acids. A legume-enriched, multicomponent intervention diet can improve metabolic health in a prediabetes population, in addition to benefits obtained from calorie restriction alone, partially mediated through changes in gut microbial composition and function. Trial registration: Clinical Trials NCT04745702.

DOP024 Transport of pks+ E. coli derived genotoxin colibactin from bacteria into host cell

Abstract Background Colorectal cancer (CRC) is among the most prevalent cancer worldwide with a rapidly increasing frequency. Many studies have highlighted a close association between CRC, inflammatory bowel diseases (IBD), and alterations in gut microbial composition. Among these, particular attention has been drawn to B2 serotype Escherichia coli and other pks-positive Enterobacteriaceae. These bacteria carry a genetic island encoding a multi-enzyme assembly line responsible for the non-ribosomal synthesis of colibactin, a peptide-polyketide hybrid molecule that acts as a potent genotoxin. Colibactin alkylates double-stranded DNA, causing inter-strand crosslinks, double-strand breaks (DSB), and a specific mutational signature commonly found in CRC. Despite the growing knowledge about colibactin synthesis and its mode of action, the mechanism by which it is delivered from bacteria to the host epithelium remains unclear. Here, we hypothesize a small-particle carriage system to overcome the instability of colibactin and the physical obstacle posed by the mucus layer. Methods Conditioned media (CM) from pks+ and isogenic pks- bacteria were harvested, filtered, and ultracentrifuged to isolate distinct fractions, including vesicle and soluble portions. These fractions were tested for their ability to induce DNA DSBs in patient-derived colon organoids, which were detected by γH2AX staining. To more closely match in vivo exposure conditions, we created apical-out converted organoids in addition to classical basal-out growth. This approach allowed us to simulate and compare exposure to surfaces accessible before and only after the loss of barrier integrity, a typical hallmark of IBD. Results Our experiments demonstrated that basal application of bacterial isolates caused increased signs of cellular stress and genetic damage, independent of colibactin. In apical-out organoids, several fractions of the cell-free bacterial supernatant, but only those derived from pks+ E. coli, were able to reliably induce double-strand breaks. Conclusion Even though the genotoxic effect following CM treatment was substantially less pronounced than in co-culture experiments, our results suggest that the transfer of colibactin between bacteria and epithelium might not depend exclusively on direct physical contact, as suspected by other studies. The data support the presence of a mid-distance carriage system that is not limited by the size of bacteria and can therefore cross the intestinal barrier. Beyond that, we demonstrated that intestinal organoids are overall more susceptible to immunological stress by bacterial components when exposed at their basal surface, which indicates a significant bias in studies relying solely on classical organoid culture as an experimental system.

Taurochenodeoxycholic Acid Improves Growth, Physiology, Intestinal Microbiota, and Muscle Development in Red Swamp Crayfish (Procambarus clarkii)

Taurochenodeoxycholic acid (TCDCA), one of the bile acids, is thought to be involved in the regulation of muscle nutrient metabolism and gut microbial homeostasis. However, the effect of dietary addition of TCDCA on Procambarus clarkii is unclear. Therefore, in this study, an 8-week feeding experiment was conducted to explore the potential regulatory mechanisms of TCDCA on P. clarkii growth, physiology, muscle quality and gut microbes. The results indicated that dietary addition of TCDCA not only improved growth performance (final weight; weight gain; and specific growth rate) but also increased muscle elasticity and protein content. In addition, dietary TCDCA promotes muscle growth and development by increasing myofiber length, which is consistent with the activation of the expression of genes related to protein utilization (TOR and AKT) and muscle proliferation and differentiation (MyHC, MLC1, MEF2A, MEF2B). Importantly, 16s rRNA sequencing demonstrated that dietary TCDCA had no significant effect on gut microbial composition (alpha diversity) but significantly increased microbial abundance at the genus level. Functional prediction analysis of differential microbes revealed that dietary TCDCA may promote metabolism by altering gut microbes, thereby promoting muscle quality. In conclusion, our study demonstrates that the dietary addition of TCDCA promotes P. clarkii growth and muscle quality and protein deposition by altering gut microbes.

Delayed feeding disrupts diurnal oscillations in the gut microbiome of a neotropical bat in captivity.

Diurnal rhythms of the gut microbiota are emerging as an important yet often overlooked facet of microbial ecology. Feeding is thought to stimulate gut microbial rhythmicity, but this has not been explicitly tested. Moreover, the role of the gut environment is entirely unexplored, with rhythmic changes to gut pH rather than feeding per se possibly affecting gut microbial fluctuations. In this study, we experimentally manipulated the feeding schedule of captive lesser long-nosed bats, Leptonycteris yerbabuenae, to dissociate photic and feeding cues, and measured the fecal microbiota and gut pH every two hours. We detected strong diurnal rhythms in both microbial alpha- and beta diversity as well as in pH within the control group. However, a delay in feeding disrupted oscillations of gut microbial diversity and composition, but did not affect rhythms in gut pH. The oscillations of some genera, such as Streptococcus, which aid in metabolizing nutrients, shifted in accordance with the delayed feeding cue and were correlated with pH. For other bacterial genera, oscillations were disturbed and no connection to pH was found. Our findings suggest that the rhythmic proliferation of bacteria matches peak feeding times, providing evidence that diurnal rhythms of the gut microbiota likely evolved to optimize their metabolic support to the host's circadian phenotype.

DOP025 Subjects sharing bacterial amplicon sequence variants exhibit differences in their IgA and IgG coating of gut bacteria, with enrichment of IgG binding for bacteria typically found in the oral cavity

Abstract Background IgA is the predominant antibody in the gut, coating a larger proportion of intestinal bacteria. IgG is found in lower concentrations but tends to increase with gut inflammation. We aimed to characterize IgA- and IgG-coated gut microbial compositions in healthy controls and evaluate coating variations of shared bacteria across individuals. Methods We established a protocol for isolating IgA- and IgG-bound fecal bacteria, using magnetic streptavidin beads coated with biotin anti-human IgA or IgG (Fig. 1A). The initial stool, as well as the negative (unbound) and positive (IgG- or IgA-bound bacteria) fractions, were analyzed by 16S rRNA sequencing. For differential abundance, a non-parametric, permutation-based rank mean test was applied (dsFDR<0.25). Results Fecal samples from 13 healthy subjects (Mean age 40.6 years, 54% males) were simultaneously incubated with anti-human IgA- or IgG- coated beads. Within-sample variability was quantified using three different fecal aliquots per subject, and several controls were included throughout the process. Paired differential abundance between the positive and the negative IgA fractions identified 46 amplicon sequence variants (ASVs) bacteria significantly higher in the positive fraction (IgA bound) and 44 ASVs significantly higher in the negative fraction. To better characterize the bound and unbound ASVs, we calculated term enrichment f-scores using the dbBact knowledge base (PMID: 37326027). This indicated enrichment of bacteria consistently reported as IgA-bound in previous publications, implicating the validity of our separation of Ig-bound bacteria (Fig. 1B). Similar analysis for the IgG-bound bacteria, identified 58 and 49 differentially abundant ASVs in the positive and negative fractions, respectively, with significant enrichment of bacteria previously noted to show IgA-coating and of salivary/oral bacteria among IgG-bound bacteria (Fig. 1C). Using the Ig-coating index (ICI; PMID: 25171403) of each `shared` ASV (detected in more than two subjects), we noted large inter-individual variance among the controls, with 42.4% ASVs showing significant inter-individual variance in IgA-coating (FDR<0.1; Fig. 2A) and 30.3% ASVs with significant inter-individual variance in IgG-coating (FDR<0.1; Fig. 2B). Conclusion Healthy subjects show variations in the immunoglobulin coating of bacteria, even among shared ASVs, indicating a personalized immune-bacterial repertoire. However, it is still unclear if this variation contributes to the gut microbiome composition variations seen between subjects. In addition, we observed preferential enrichment for immunoglobulin coating of bacteria typically found in the oral cavity.

P1314 Multi-omics analysis of Crohn’s Disease trajectory from active to remission reveals that the altered ileal anti-bacterial epithelial signals and pathogenic microbial composition and metabolomics persist despite normalizing ileal immune signals during remission

Abstract Background Characterizing gut factors that improve or persist during Crohn’s disease (CD) trajectory from active to remission to healthy-normal states is crucial for defining treatment targets and CD cure. Methods Using multi-omics (ileal transcriptomics, microbiome, and metabolomics), we aimed to compare active, mostly treatment naïve newly diagnosed CD to patients in remission, using controls as a reference Results 193 subjects were included (median age 32 years, 60% male); 78 CD in remission, 38 active and mostly (80%) treatment naïve newly diagnosed CD patients, and 77 non-IBD controls (Table 1). Controls and CD remission groups had significantly lower and mostly normal CRP, with significantly lower fecal calprotectin in the remission than in the active group (Table 1). Most patients (79%) in remission were on biologics (58% on anti-TNF and 21% on vedolizumab/Stelara). Ileal transcriptomics (Fig. 1A-B) highlighted a significant reduction of genes and pathways related to adaptive T cell activation in treated patients in remission compared to active treatment naïve patients. This decrease was significantly lower than in controls, suggesting some immune compromise likely secondary to CD therapy. There were no differences between the levels of S1008/9 genes encoding for fecal calprotectin and OSM and TREM1 genes related to the anti-TNF response in patients in remission on treatment, compared to controls. Despite that, patients in remission still showed persistent signals of elevated expression of epithelial antimicrobial pathways and genes, including DUOX2, CEACAM5/6, REG4, and DMBT1, and more novel increased goblet cells and mucin glycosylated genes and signals (Fig. 1A-B). Interestingly, these epithelial antimicrobial signals during remission were coupled with persistent pathogenic gut microbial composition, as indicated by several microbial measurements, including the published Gevers et al index (PMID:24629344), our general health and specific IBD indexes (PMID:35197084), and alpha diversity (Fig. 1C), with significant enrichment of oral bacteria that dislocated to the gut in the CD groups. Similarly, 39 of 43 (91%) of the gut metabolites (Fig. 1D) that were significantly different between CD in remission vs. controls showed similar altered directionally in active treatment naïve CD patients vs. controls, suggesting persistent metabolic alterations during remission Conclusion Multi-omics analysis shows that despite normalizing ileal immune signals and genes encoding calprotectin during remission, the altered anti-bacterial epithelial signal and pathogenic microbiome and metabolome signatures persist. This highlights the need to directly target the epithelia-microbes axis, in addition to immune suppression, to improve CD outcomes.

Chronic restraint stress affects the diurnal rhythms of gut microbial composition and metabolism in a mouse model of depression

BackgroundDepression is a common mental disorder accompanied by gut microbiota dysbiosis, which disturbs the metabolism of the host. While diurnal oscillation of the intestinal microbiota is involved in regulating host metabolism, the characteristics of the intestinal microbial circadian rhythm in depression remain unknown. Our aim was to investigate the microbial circadian oscillation signature and related metabolic pathways in a mouse model with depression-like behaviours.MethodsChronic restraint stress (CRS) was used to induce depressive-like behaviours in C57BL/6J mice. The open field test (OFT) and forced swimming test (FST) were used to evaluate anxiety- and depressive-like behaviours in the control and CRS groups. Afterwards, faecal samples from the two groups were collected every four hours from ZT2 (9:00 am) to ZT22 (5:00 am). Faecal 16 S rRNA gene sequencing and metabolomics analysis were performed, and the microbial circadian rhythm was analysed via the MetaCycle package in R/RStudio.ResultsCRS mice exhibited depressive-like behaviours after 4 weeks of restriction. Alpha- and beta-diversity analyses revealed that the microbial composition in control and CRS mice oscillated throughout the day. The circadian rhythm analyses revealed that at the phylum level, Bacteroidota, Firmicutes, Cyanobacteria and Patescibacteria showed circadian rhythmicity in the CRS group. At the genus level, Dubosiella and Romboutsia showed circadian rhythmicity in the control group, and Dubosiella abundance was correlated with tryptophan and galactose metabolism. In the CRS group, Bacteroides, Parabacteroides, and Rikenellaceae_RC9_gut_group showed circadian rhythmicity; among these genera, Parabacteroides was related to tryptophan metabolism, axon regeneration, phenylalanine metabolism and tyrosine metabolism.ConclusionOur data highlight the importance of observing the diurnal oscillation of the microbiome in host with depressive-like states. Rhythmicity in the microbiome may affect the host by regulating distinct metabolic pathways during the light and dark phases. A better combination of microbiota composition and oscillation would help to offer novel insight into key genera and their potential effects on depression.

The perinatal microbiota-gut-brain axis: Implications for postpartum depression.

Pregnancy and childbirth are accompanied by widespread maternal physiological adaptations and hormonal shifts, that have been suggested to result in a period of vulnerability for the development of mood disorders such as postpartum depression (PPD). There is also evidence of peripartum changes in the composition of the gut microbiota, but the potential contribution of intestinal microbes to the adaptations, or subsequent vulnerabilities, during this period are unknown. Here we outline key pathways involved in peripartum adaptations including GABAergic signaling, oxytocin and immunomodulation that are also associated with susceptibility to mood disorders and present evidence that these pathways are modulated by gut microbes. We also discuss the therapeutic potential of the microbiota-gut-brain axis in postpartum depression and identify future directions for research to help realize this potential. Peripartum adaptations are associated with shifts in gut microbial composition. Disruption of GABAergic, oxytocin and immunomodulatory pathways may contribute to vulnerability of mood disorders including postpartum depression. These key adaptative pathways are modulated by intestinal microbes suggesting a role for the gut microbiota in determining susceptibility to PPD. More research is needed to confirm relationship been gut microbes and PPD and to gain the mechanistic understanding required to realize the therapeutic potential of microbiota-gut-brain axis in this mood disorder.

Benzoic Acid, Enterococcus faecium, and Essential Oil Complexes Improve Ovarian and Intestinal Health via Modulating Gut Microbiota in Laying Hens Challenged with Clostridium perfringens and Coccidia

Intestinal disease is becoming increasingly prevalent in poultry production; however, the effect of BEC in laying hens challenged with C. perfringens and coccidia is limited. This study aimed to investigate the effects of dietary supplementation with BEC on intestinal and ovarian health in laying hens challenged with C. perfringens and coccidia. A total of 80 Lohmann gray hens (35 weeks) were randomly assigned to two dietary groups supplemented with BEC (0 or 1000 mg/kg). Each group contained 40 replicates, with one bird each (one hen per cage). During the sixth week of the trial, half of the laying hens in each group (n = 20) were administered 40 mL C. perfringens (2.5 × 1010 CFU/mL) and 0.15 mL coccidia (55,000 sporangia/mL), while the other half (n = 20) were administered 40 mL phosphate-buffered saline (PBS). The results indicated that those challenged with C. perfringens and coccidia had severely damaged jejunal and ovarian histopathological morphology, increased oxidative damage, decreased cecal acetic acid and butyric acid content (p < 0.05), and resulted in lower gut microbial richness and diversity. The diet of 1000 mg/kg BEC reduced the jejunal and ovarian pathological damage and oxidative damage, increased short-chain fatty acids (SCFAs) content, and enhanced gut microbial richness and diversity (p < 0.05) in laying hens challenged with C. perfringens and coccidia. Furthermore, the positive effects of BEC on intestinal health were associated with changes in gut microbial composition and structure. In summary, dietary supplementation with BEC has the potential to reduce the severity of intestinal and ovarian damage caused by challenges posed by C. perfringens and coccidia through the modulation of gut microbiota.

Fecal occult blood affects intestinal microbial community structure in colorectal cancer

BackgroundGut microbes have been used to predict CRC risk. Fecal occult blood test (FOBT) has been recommended for population screening of CRC.ObjectiveTo analyze the effects of fecal occult blood test (FOBT) on gut microbes.MethodsFecal samples from 107 healthy individuals (FOBT-negative) and 111 CRC patients (39 FOBT-negative and 72 FOBT-positive) were included for 16 S ribosomal RNA sequencing. Based on the results of different FOBT, the community structure and diversity of intestinal bacteria in healthy individuals and CRC patients were analyzed. Characteristic gut bacteria were screened, and various machine learning algorithms were applied to construct CRC risk prediction models.ResultsThe gut microbiota of healthy people and CRC patients with different fecal occult blood were mapped. There was no statistical difference in diversity between CRC patients with negative FOBT and positive FOBT. Bacteroides, Blautia and Escherichia-Shigella were more correlated to healthy individuals, while Streptococcus showed higher correlation with CRC patients with negative FOBT. The accuracy of CRC risk prediction model based on the support vector machines (SVM) algorithm was the highest (89.71%). Subsequently, FOBT was included as a characteristic element in the model construction, and the prediction accuracy of the model was all increased. Similarly, the CRC risk prediction model based on SVM algorithm had the highest accuracy (92%).ConclusionFOB affects the community composition of gut microbes. When predicting CRC risk based on gut microbiome, considering the influence of FOBT is expected to improve the accuracy of CRC risk prediction.

Does preeclampsia impact the gut microbiota of preterm offspring during early infancy?

Preeclampsia (PE) is a pregnancy complication characterized by high blood pressure and organ damage. This study investigates the differences in the gut microbiota between preterm neonates born to mothers with PE and those born to mothers without PE (PR), aiming to understand how maternal health conditions like PE influence neonatal gut microbiota. The early gut microbiota plays a crucial role in neonatal health, and disturbances in its development can have long-term consequences. Fecal samples were collected from preterm neonates of PE and PR mothers at 2 and 6 weeks postpartum and analyzed using shotgun metagenomic sequencing. We found that PE significantly affected the gut microbial composition of preterm neonates, particularly at 2 weeks postpartum. The gut microbial diversity in the PE_2 group was notably lower compared to the PR_2 group, with no significant difference observed between the PR_6 and PE_6 groups. At the phylum level, Firmicutes and Proteobacteria were predominant, with significant differences observed, particularly a lower abundance of Actinobacteria in the PE_2 group. At the genus level, Escherichia, Enterococcus, and Klebsiella were more prevalent in the PE_2 group, whereas Bifidobacterium and Cutibacterium dominated the PR_2 group. The gut virome analysis showed no significant differences among the groups. Functional analysis revealed distinct metabolic pathway activities across the groups, suggesting that early disturbances due to PE impact the establishment of healthy gut microbiota. These findings underscore the substantial influence of maternal health on the early development of the neonatal gut microbiota and highlight the potential long-term health consequences. Additionally, the differences in metabolic pathways further emphasize the impact of preeclampsia on gut microbiota functionality.