Intestinal Disorders Research Articles

Diet-Microbiome-ENS connection: Impact of the Cafeteria Diet.

The interplay between diet-induced obesity and gastrointestinal dysfunction is an evolving area of research with far-reaching implications for understanding the gutbrain axis interactions. In their study, Ramírez-Maldonado et al. employ a cafeteria (CAF) diet model to investigate the effects on gut microbiota, enteric nervous system (ENS) integrity and function, and gastrointestinal motility in mice. Their work provides notable insights while also presenting opportunities for further exploration. The findings highlight early shifts in gut microbiota composition, notably increased Clostridia and Proteobacteria populations, and their association with ENS remodeling and motility impairment. This innovative use of a CAF diet strengthens the relevance of the model to real-world dietary patterns. Future studies will determine the mechanisms linking these microbial changes to neuronal dysfunction, particularly in terms of excitability deficits. The longitudinal approach is a commendable aspect of the study, yet certain dimensions, such as sex-specific responses and long-term outcomes, are underexplored. Further emphasis on these factors could provide a more nuanced understanding of the dietary effects on gastrointestinal health. While inflammation is identified as a mediator, more in-depth analysis of the pathways involved would help substantiate its role in ENS remodeling. Overall, this study makes a valuable contribution to the field, offering a solid foundation for future research. Expanding on the mechanistic insights and addressing the outlined gaps could further the translational relevance of these findings in tackling obesity-related gastrointestinal disorders.

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.

New therapies in celiac disease.

Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing. Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten. While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.

Nutraceutical Impact of Pumpkin Seed Oil on Expression Levels of EZH-2 and KRT-14 Genes against DSS-induced Inflammatory Bowel Disease in the Rat Model.

Inflammatory bowel disease is a collection of intestinal disorders that cause inflammation in the digestive tract. Prolonged inflammation in the gastrointestinal tract is a major risk factor for colorectal cancer. The objective of this study was to fucus on gene expression levels of (KRT-14; associated with epithelial cell integrity) and enhancer of zeste homolog-1 (EZH-2; involved in cellular proliferation) in a IBD rat model in order to rule out impact of nutraceuticals (pumpkin seed oil; PSO) as a complementary approach to conventional treatments of IBD. In the current study, IBD was induced using dextran sodium sulfate (DSS). Following acclimatization, rats were separated into three groups: the negative control, the positive control, and the treatment group. The DSS (1 ml/kg bw) was given to the positive control and treatment groups. Negative control was given only a normal diet. Pumpkin seed oil (PSO) was given orally as a treatment (0.5 ml/kg bw). Blood and colon tissue were obtained on the 5th, 10th, 14th, and 18th days. Physical parameters, hematology, biochemical assays, gene expression, and histopathology were carried out. After statistical analyses, macroscopic parameters showed significant differences. Biochemical analyses revealed a significant (P ≤ 0.05) decrease in serum potassium concentrations, total cholesterol, triglycerides, total proteins, total oxidants status, and C-reactive proteins in PSO treated group as compared with positive control. Gene expression levels of KRT-14 and EZH2 were significantly (P ≤ 0.05) upregulated in PSO treated group as compared to positive control group. Histopathology revealed that pumpkin seed oil preserved the structural integrity of colon.

The Gut-Brain Connection: Investigating the Correlation between Autism Disorder and Gut Bacterium

Autism Spectrum Disorder (ASD) is a type of developmental disability which results in social and communication difficulties besides exhibiting stereotyped or repetitive use of objects and bodies. ASD is becoming increasingly prevalent as a significant public health issue, impacting 1 in 100 children globally and showing an apparent increase in cases internationally. Up to 80% of children with ASD experience gastrointestinal (GI) dysfunction, indicating a potential connection between gut microbiota and the development of ASD. This study aims to define the link between gut dysbiosis and ASD and look into the effectiveness of the therapies which use the microbiota, including probiotics, prebiotics, and MTT. A literature review was carried out to identify literature published on Scopus, MEDLINE, and PubMed that focused on paediatric population, and the types of interventions included dietary changes and FMT. Growing evidence for the changed gut microbiota of children with ASD reveals the higher level of Clostridium and the lower level of Bifidobacterium population. Supplements of other types of microbes such as probiotics had mixed outcomes in impacting ASD behaviours but positively impacted the gastrointestinal manifestations. The research identifies changes in the gut bacterial makeup of children with ASD, showing increased levels of Clostridium and Sutterella, which play a significant role in gastrointestinal and behavioral issues. Therapies aimed at the microbiota, such as probiotics and dietary changes, and fecal microbiota transplantation (FMT) demonstrated the ability to enhance symptoms associated with GI issues and ASD.

Selenomethionine Attenuates Aflatoxin B1-induced Liver Injury by Modulating the Gut Microbiota and Metabolites in Rabbits.

Dietary contamination with aflatoxin B1 (AFB1), which can lead to severe liver damage, poses a great threat to livestock and poultry breeding and has detrimental impacts on food safety. Selenomethionine (SeMet), with anti-inflammatory, antioxidative, and detoxifying effects, is regarded as a beneficial food additive. However, whether SeMet can reduce AFB1-induced liver injury and intestinal microbial disorders in rabbits remains to be revealed. Forty 35-day-old rabbits were randomly divided into a control group, an AFB1 group, and 0.2 mg/kg Se and 0.4 mg/kg Se groups. The SeMet treatment group was fed different doses of the SeMet diet every day for 21 days. On Days 17-21, the AFB1 group, 0.2 mg/kg Se, and 0.4 mg/kg Se groups were intragastrically administered 0.3 mg AFB1/kg b.w. Results showed that SeMet restored alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, alleviating AFB1-induced liver function damage. This was linked to changes in intestinal metabolites and activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. In this study, the relationships between intestinal microorganisms and their metabolites and AFB1-induced liver injury are investigated, and the potential protective role of SeMet against liver damage induced by AFB1 offers novel insights into strategies for the prevention and treatment of AFB1-related toxicity.

Effects of Salmonella Typhimurium infection on intestinal flora and intestinal tissue arachidonic acid metabolism in Wenchang chickens

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether arachidonic acid (ARA) metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and ARA metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), lipoxin A4 (LXA4), ± 8(9)-EET, ± 11(12)-EET, and ± 8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (Phospholipase A2 PLA2 and Cyclooxygenase-2 COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including Interferon-γ (IFN-γ), Transforming growth factor-β1 (TGF-β1), Interleukin-4 (IL-4), and Interleukin-6 (IL-6). In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. The present study revealed the structure of cecal flora in S. Typhimurium-infected Wenchang chickens. In addition, this study demonstrated that S. Typhimurium activates the ARA cyclooxygenase metabolic pathway, which in turn mediates the development of intestinal inflammation in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

Post-infectious irritable bowel syndrome: Focus on serotonin metabolism disturbances and gut microbiota modulation

Post-infectious irritable bowel syndrome (PI–IBS) is the first phenotype of the disease described in the literature and the most studied to date. The prevalence of PI–IBS in the population continues to grow steadily especially in the post-COVID-19 pandemic period. Taking into account the accumulated scientific and clinical data dysfunction of the functional axis «microbiota-gut-brain» associated with the formation of visceral hypersensitivity and intestinal motor disorders due to abnormal serotonin metabolism, increased intestinal permeability and low-grade inflammation is considered as a key pathogenetic factor underlying the development and persistence of PI–IBS symptoms. This review article analyzes and summarizes information on the mechanisms of PI–IBS associated with changes in neurohumoral regulation, as well as the qualitative and quantitative composition of the intestinal microbiota. In addition, data on the possibility of using probiotic therapy in the complex therapy of patients with PI–IBS are presented.

A multidimensional fecal microbial and inflammatory biomarker profiling in preterm and full-term neonates.

Preterm birth affects approximately one in every ten neonates. The clinical outcomes depend on care and management factors, including the birth delivery method and the use of antibiotics. This observational cohort study determined antimicrobial peptides, proteases, metabolomic, and microbiome profiles in fecal samples collected from 20 preterm and nine full-term neonates 48 h after birth. The results show that preterm neonates have increased levels of α-defensins, serine proteases, and matrix metalloproteinases. They also have distinct metabolic signatures characterized by decreased kynurenic acid and increased mevalonate levels. These neonates also exhibit reduced microbial diversity. This study highlights that heightened immune response and proteolytic activity, marked dysbiosis, and reduced short-chain fatty acids within the preterm gastrointestinal tract immediately after birth might predispose neonates to exacerbated gut inflammation. Some of the findings, including the elevated fecal mevalonate levels, are potential biomarkers in neonatology for early identification of metabolic disturbances linked to gut inflammation, emphasizing further studies to explore its association with inflammatory conditions in preterm infants. Inflammatory markers that can predict intestinal disorders are insufficiently characterized in preterm neonates. This study identified antimicrobial peptide responses, proteolytic activity, marked dysbiosis, and reduced short-chain fatty acid production in feces from preterm neonates. These critical differences in inflammatory, metabolomic, and microbial signatures may predispose to exacerbated gut inflammation in preterm neonates. Some inflammatory effectors in feces are potential biomarkers for the early detection of intestinal inflammatory conditions in preterm neonates. This study contributes to understanding the inflammatory conditions in the guts of preterm babies and identifies novel targets for timely diagnosis, interventions, and management practices in neonatal care.

Mannuronate Oligosaccharides Ameliorate Experimental Colitis and Secondary Neurological Dysfunction by Manipulating the Gut-Brain Axis.

Microbiota dysfunction induces intestinal disorders and neurological diseases. Mannuronate oligosaccharides (MAOS), a kind of alginate oligosaccharide (AOS), specifically exert efficacy in shaping gut microbiota and relieving cognitive impairment. However, the key regulatory factors involved, such as the specific strains and metabolites as well as their regulatory mechanisms, remain unclear at present. This research investigates how MAOS specifically impact the gut-brain axis in vivo and in vitro. The results showed that pretreatment with MAOS significantly ameliorated dextran sodium sulfate (DSS)-induced colitis and secondary nerve injury. This preventive mechanism operates through the regulation of serum DOPC abundance and the gut-brain axis, achieved by inhibiting the TLR4/MyD88/NF-κB pathway. These findings underscore the crucial role of dietary MAOS in the prevention of colitis and neurological disorders, providing a rationale for the application of MAOS in disease prevention and functional food ingredients.

P0874 Efficacy and tolerability of anti-tumor necrosis factor alpha therapy in refractory intestinal Behçet’s disease

Abstract Background Intestinal Behçet’s disease (BD) is a rare chronic intestinal vasculitic disorder and it is often refractory to conventional therapies such as corticosteroids and immunomodulators. We aimed to assess the efficacy and tolerability of anti-tumor necrosis factor alpha (TNF ɑ) in patients with moderate to severe intestinal BD who refractory to conventional therapy. Methods We analyzed patients with intestinal BD treated with anti-TNF ɑ more than 4 months registered at the Inflammatory Bowel Disease Clinic of Severance Hospital, Seoul, Korea. Clinical remission rates, clinical response rates, biological response rates at 4, 12, 24 months, and adverse events of anti-TNF ɑ treatment were investigated. We also examined relapse rates and predictive factors of relapse based on the BD-related surgery and admission. Results A total of 119 patients with intestinal BD were selected for the anti-TNF ɑ therapy, 15 (12.6%) were bio-exposed patients, 68 (57.1%) received concomitant immunomodulatory therapy, and 56 (47.1%) received concomitant corticosteroids at anti- TNF ɑ induction. At 4, 12, and 24 months after anti-TNF ɑ therapy, clinical remission rates were 23.5%, 40.3%, and 42%; clinical response rates were 84.0%, 62.2%, and 62.2%; and biological response rates were 61.3%, 68.9%, and 58.8%, respectively. Sixty-three (52.9%) patients presented disease relapse during follow-up period. The mean time before relapse was 2.8 years (median, 1.8 years). Higher initial CRP (hazards ratio [HR]: 1.013, 95% CI: 1.008-1.018, p < 0.001), previous surgery (HR: 4.282, 95% CI: 2.379-7.709, p < 0.001), concomitant immunomodulator (HR: 0.455, 95% CI: 0.27-0.775, p = 0.004), and clinical response at 4 months (HR: 0.353, 95% CI: 0.181-0.687, p = 0.002) were independent factors associated with the disease relapse in multivariate Cox regression analysis. There was no mortality in using anti-TNF ɑ agent. Twenty-six (21.8%) patients experienced infection, and 3 (2.5%) patients experienced infusion reaction. Conclusion Anti-TNF ɑ therapy could be a useful therapeutic option for refractory intestinal BD with an acceptable efficacy and tolerability profiles.

P0070 Distinct Serum Proteome Alterations Following Vedolizumab and Ustekinumab Therapy in IBD Patients

Abstract Background Inflammatory bowel disease (IBD) is a chronic intestinal disorder characterized by relapse and remission. Dysregulated cytokine networks and excessive immune activation drive intestinal inflammation. Therapies targeting cytokines (e.g., TNF, IL-12/23) and immune cell trafficking (e.g., integrin inhibitors) have been effective. However, the impact of anti-integrin (vedolizumab) and anti-IL-12/23 (ustekinumab) therapies on systemic inflammation is poorly understood. This study compares serum proteome profiles of patients treated with vedolizumab or ustekinumab to elucidate their distinct effects on inflammatory pathways. Methods This study included patients with Crohn’s disease (CD), ulcerative colitis (UC), and age- and sex-matched healthy donors (HD), who received either ustekinumab or vedolizumab treatment. The ustekinumab cohort comprised 23 CD and 10 UC patients, while the vedolizumab cohort included 7 CD and 27 UC patients. Serum samples were collected from ustekinumab-treated patients at baseline (week 0) and 8 weeks post-treatment, and from vedolizumab-treated patients at baseline (week 0) and 6 weeks post-treatment. Additionally, serum samples were collected from 32 healthy donors. Proteomic analysis was performed using the Olink Inflammation Panel, measuring 92 inflammation-related proteins. Differential protein expression analysis was conducted to compare baseline and post-treatment samples within each cohort. Results Serum proteomic analysis using the Olink Inflammation panel revealed significant alterations in the levels of 15 proteins in IBD patients compared to healthy controls. Pro-inflammatory markers, including 4E-BP1, SIRT2 and TNF were significantly upregulated, indicating immune activation in IBD. Conversely, anti-inflammatory regulators, such as LIF-R and SCF, were significantly downregulated. Ustekinumab treatment led to upregulation of IL-12B and downregulation of 4E-BP1, SIRT2. Notably, IL-12B was upregulated in both CD and UC, while 4E-BP1 and SIRT2 were downregulated in CD (week 8 vs week 0). Conversely, vedolizumab treatment induced robust proteomic changes over time. Between week 0 and week 6, majority of proteins showed significant differential expression, more than the differences observed between IBD and HD groups. Conclusion Serum proteomic profiles of IBD patients differ from healthy donors. Ustekinumab induced minimal serum changes, indicating a limited systemic effect, while vedolizumab led to substantial proteomic shifts, suggesting broader modulation of inflammation. These distinct effects highlight the differing mechanisms of ustekinumab and vedolizumab on systemic inflammation in IBD, prompting further investigation to optimize therapeutic strategies.

Disrupted Paraventricular Hypothalamic Nucleus Functional Connectivity in Parkinson's Disease With Constipation.

Constipation is one of the most common non-motor symptoms in patients with Parkinson's disease (PD), which could manifest during the early stage of the disease. However, the etiology of constipation in PD remains largely unknown. Previous studies supported that gastrointestinal dysfunction may be associated with functional connectivity alterations in paraventricular hypothalamic nucleus (PVN). Therefore, this study aimed to investigate the potential contribution of the PVN to the pathogenesis of constipation in a cohort of early-stage patients with PD and to compare brain network organization between PD patients with and without constipation. A total of 66 PD patients (PD with constipation and without constipation) and 30 healthy controls were prospectively enrolled. All participants acquired T1-weighted and resting-state fMRI scans. Then we employed voxel-based morphometry analysis and functional connectivity analysis. We observed a decreased functional connectivity in the PVN-pontine tegmentum pathway in PD patients with constipation compared to the patients without constipation (p = 0.006, t = 5.37), while we did not find any changes in basal ganglia circuitry between these two groups. In addition, we found that the functional connectivity between PVN and pontine tegmentum was negatively associated with the UPDRS I, II, III and NMSS scores (p < 0.05). Meanwhile, these two types of patients also showed substantial differences in functional connections linking the inferior frontal gyrus and cerebellum with multiple brain regions. We discovered no statistical difference in gray matter volume among these two groups. Our study provides further insights into the dysfunctional mechanisms of constipation, suggesting that abnormal PVN functional connectivity may be related to the mechanism of constipation in PD. Meanwhile, the inferior frontal gyrus and cerebellum may be involved in the occurrence of constipation in PD patients.

Traditional Chinese medicine in the treatment of Helicobacter pylori-related gastritis: The mechanisms of signalling pathway regulations

Helicobacter pylori -associated gastritis (HPAG) is a common condition of the gastrointestinal tract. However, extensive and long-term antibiotic use has resulted in numerous adverse effects, including increased resistance, gastrointestinal dysfunction, and increased recurrence rates. When these concerns develop, traditional Chinese medicine (TCM) may have advantages. TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body. It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication. This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways, which reflects the flexibility of TCM in treating diseases and the advantages of multi-level, multi-pathway, and multi-target treatments for HPAG.

Metabolics-Based Study on the Therapeutic Mechanism Behind the Effect of Shenhuang Plaster Applied to the Shenque Acupoint on Gastrointestinal Motility in POI Mice.

Postoperative ileus (POI) is a common postoperative clinical complication that significantly affects postoperative rehabilitation and quality of life in patients and can even produce secondary complications, leading to serious consequences. External treatment using Shenhuang Plaster (SHP) (Shenque acupoint administration) has definite effects and unique advantages in the prevention and treatment of POI, but its mechanism is not completely clear. In this study, we investigated the therapeutic mechanism behind the effect of Shenhuang Plaster applied to the Shenque acupoint on gastrointestinal motility in POI mice based on metabolomics. C57BL/6 mice were divided into three groups: blank control (Ctrl), model (POI), and intervention (POI + SHP) groups. SHP treatment was started 3 days before modeling. We employed several behavioral tests and gastrointestinal transit function measurements and performed qRT-PCR analysis, 16S rRNA gene sequencing, and metabolomics analysis on serum metabolites. We found that SHP could reduce the mRNA expression of inflammatory mediators in the smooth muscle tissue of the small intestine, regulate the structure and function of the intestinal microbiota, and modulate serum phenylalanine, carnitine, and glutamic acid levels. POI mice had obvious intestinal flora disorders and metabolic disorders of amino acids and their derivatives, and there was a significant correlation between differential flora and differential metabolites. SHP could effectively regulate the concentration of intestinal flora and serum metabolites and the metabolic pathway related to amino acids in vivo and, ultimately, achieve a therapeutic purpose in POI. In this study, it was found, for the first time, that applying SHP to the Shenque acupoint could effectively regulate the serum metabolites of phenylalanine, carnitine, and glutamate, and improve postoperative intestinal motile disturbance through association with the intestinal flora.

Tracking changes in autonomic function by coupled analysis of wavelet-based dispersion of heart rate variability and gastrointestinal symptom severity in individuals with hypermobile Ehlers–Danlos syndrome

IntroductionPeople with hypermobile Ehlers–Danlos syndrome (hEDS) experience multisystemic dysfunction with varying severity and unpredictability of flare occurrence. Cohort studies suggest that individuals with hEDS have a higher risk for autonomic dysfunction. The gold standard for assessing autonomic function, clinically, is the heart rate variability (HRV) assessment from 24-h Holter monitor electrocardiogram data, but this is expensive and can only be performed in short durations. Since their advent, biometric devices have been a non-invasive method for tracking HRV to assess autonomic function. This study aimed to understand the intra- and inter-individual variability in autonomic function and to associate this variability with gastrointestinal symptoms in individuals with hEDS using wearable devices.MethodsWe studied 122 days of biometric device data from 26 individuals, including 35 days highlighted as high gastrointestinal (GI) dysfunction and 48 days as low GI dysfunction. Utilizing wavelet analysis to assess the frequency domains of heart rate signals, we compared participants’ HRV data for high, low, very low (VLF), and ultralow (ULF) frequency domains associated with physiological differences.ResultsWe found a significant difference between the VLF and ULF signals on high-GI symptom days compared with low-symptoms days for 92 and 76% of the signals sampled, respectively.DiscussionOur pilot data show a change in HRV for individuals with hEDS experiencing a flare day for a single-body system. Future research will focus on evaluating the relationship between longitudinal multisystemic symptom severity fluctuations and HRV.

Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.

Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.

Mutual influence of clinical manifestations of intestinal disorders and intestinal microbiot indicators in patients with deep endometriosis

Summary. Endometriosis is a chronic multifactorial disease that affects more than 170 million women of reproductive age worldwide, causing pelvic pain syndrome, dyspareunia, and symptoms of gastrointestinal dyspepsia, thereby having a negative impact on the psycho-emotional state of patients. Despite a wide range of medical and surgical treatments, the relapse rate reaches 50%, which is a global economic and social problem.The purpose of the study. to evaluate the mutual influence of clinical manifestations of intestinal disorders and the state of the intestinal microbiota in patients with deep endometriosis.Materials and methods. The study included 83 patients of reproductive age who underwent surgical treatment of common forms of external genital endometriosis. The first group consisted of 32 patients of reproductive age who underwent repeated surgical treatment due to relapse of deep infiltrative endometriosis, the second group — 51 patients without relapse of the disease one year after the primary operation, due to deep infiltrative endometriosis, the third group — 30 patients of reproductive age. not suffering from external genital endometriosis. An analysis of the somatic anamnesis was carried out, as well as questionnaire data on pelvic pain on a visual analogue scale (VAS) and functional bowel disorders in patients with deep infiltrating endometriosis, depending on the status of relapse of the disease. The composition of the intestinal microbiota was assessed by quantitative real-time PCR using a test system for determining the DNA of intestinal-associated microorganisms.Results and discussion. The results of the study demonstrate bidirectional relationships between clinical and microbiological parameters and the recurrent course of deep endometriosis. Patients of the main group significantly more often suffered from functional diseases of the gastrointestinal tract, the spectrum of which was represented by chronic gastritis and irritable bowel syndrome. Correlation relationships between indicators of the Bacillota domain of the intestinal microbiota and clinical and anamnestic indicators of gastrointestinal pathology, the values of questionnaire scales in patients with deep endometriosis demonstrate moderate positive relationships between the weight of patients and the number of Lachnospiraceae (r = 0.63299), symptoms of bloating and the number Streptococcus spp (r=0.67402). Correlation relationships between indicators of the Bacteroidota domain of the intestinal microbiota and corresponding indicators demonstrate strong positive relationships between the amount of E.Coli in the intestinal microbiota and the level of pain assessed on the VAS scale after 1 (r = 0.62366) and 3 months (r = 0. 72598) after surgery. Moderate positive correlations were revealed between the number of Enterobacterales in the intestinal microbiota and the level of pain assessed on the VAS scale 1 (r=0.58169) and 3 months (r=0.57706) after surgery.Conclusions. The recurrent course of endometriosis is accompanied by functional intestinal disorders, the manifestations of which persist after surgical treatment, which is mediated by changes in the intestinal microbiota. In patients with recurrent deep endometriosis, a decrease in the species and taxonomic diversity of the intestinal microbiota was found, due to an increase in the Bacillota/Bacteroidota ratio, the number of pathobionts, and a decrease in the number of commensal bacteria of the genus Bifidobacterium spp. These clinical and microbiological parallels demonstrate the need to harmonize the intestinal microbiota as a comprehensive prevention of disease relapse.

Peripheral blood immune cells from individuals with Parkinson's disease or inflammatory bowel disease share deficits in iron storage and transport that are modulated by non-steroidal anti-inflammatory drugs.

Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated in PD pathogenesis. Although alterations in circulating inflammatory cytokines and reactive oxygen species (ROS) have been associated with PD, no biomarkers have been identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, which involves perturbation of the underlying immune system, is an early and often-overlooked symptom that affects up to 80 % of individuals living with PD. Interestingly, 50-70 % of individuals with inflammatory bowel disease (IBD), a GI condition that has been epidemiologically linked to PD, display chronic illness-induced anemia - which drives toxic accumulation of iron in the gut. Ferroptotic (or iron loaded) cells have small and dysmorphic mitochondria-suggesting that mitochondrial dysfunction is a consequence of iron accumulation. In pro-inflammatory environments, iron accumulates in immune cells, suggesting a possible connection and/or synergy between iron dysregulation and immune cell dysfunction. Peripheral blood mononuclear cells (PBMCs) recapitulate certain PD-associated neuropathological and inflammatory signatures and can act as communicating messengers in the gut-brain axis. Additionally, this communication can be modulated by several environmental factors; specifically, our data further support existing literature demonstrating a role for non-steroidal anti-inflammatory drugs (NSAIDs) in modulating immune transcriptional states in inflamed individuals. A mechanism linking chronic gut inflammation to iron dysregulation and mitochondrial function within peripheral immune cells has yet to be identified in conferring risk for PD. To that end, we isolated PBMCs and simultaneously evaluated their directed transcriptome and bioenergetic status, to investigate if iron dysregulation and mitochondrial sensitization are linked in individuals living with PD or IBD because of chronic underlying remittent immune activation. We have identified shared features of peripheral inflammation and immunometabolism in individuals living with IBD or PD that may contribute to the epidemiological association reported between IBD and risk for PD.

Modern Experience in Pharmacotherapy of Irritable Bowel Syndrome in Children

This review examines modern approaches to the diagnosis and treatment of irritable bowel syndrome (IBS) in children, one of the most common functional disorders of the gastrointestinal tract. IBS is characterized by chronic abdominal pain, intestinal motility disorders and stool changes, which significantly reduces the quality of life of patients. The article analyzes in detail the pathogenetic mechanisms of IBS, including the role of the gut–brain axis, gut microbiota and neuroendocrine factors. Special attention is paid to the pharmacotherapy of IBS in children, including the use of antidepressants, probiotics and herbal components, as well as the role of correctors of the motor activity of the digestive tract in relieving symptoms. Modern recommendations on the use of various classes of antidepressants are considered, taking into account their pharmacokinetic and pharmacodynamic characteristics. The prospects of using probiotics and herbal preparations in the complex therapy of IBS are also analyzed. The data obtained confirm the need for a personalized approach to the treatment of IBS, taking into account the genetic and physiological characteristics of patients.