Search Results (576)

Background/Objectives: Quality of life (QoL) and functional recovery are essential outcomes in patients undergoing rectal cancer surgery. In addition to oncological results, bowel dysfunction and stoma-related issues may significantly affect postoperative well-being. We aimed to evaluate QoL changes at 1 and 6 months postoperatively and functional outcomes in rectal cancer patients who underwent curative surgical treatment, sphincter-preserving surgeries (SPS) or abdominoperineal resection (APR). Owing to its impact on QoL, several functions were assessed using the Low Anterior Resection Syndrome (LARS) score. Methods: This retrospective observational study consisted of 99 patients who underwent curative rectal cancer surgery, of which 38 patients had colostomy, and 61 no colostomy. To assess patient-reported outcomes related to QoL, the EORTC QLQ-C30 questionnaire, QLQ-CR29 questionnaire, and LARS instrument were sent to the patients at 1 and 6 months postoperatively. Changes over time were analyzed using paired statistical tests, and subgroup analyses were performed according to colostomy status and surgical approach. Results: Significant improvements were observed in the global health status and all major functional domains between 1 and 6 months postoperatively. The global health status increased from 74.9% to 86.5% (p < 0.001). Symptom burden decreased significantly, particularly for fatigue (−18.31), pain (−14.48), diarrhea (−12.46), and insomnia (−11.45), representing clinically meaningful improvements. Patients who underwent abdominoperineal resection or resection with colostomy had lower QoL scores at 1 month but showed substantial improvement at 6 months, becoming comparable to those who underwent SPS. LARS outcomes demonstrated progressive functional recovery, with the proportion of patients without LARS increasing from 39 to 46, while major LARS decreased from 7 to 3 patients. However, approximately 40% of patients in the SPS group continued to report moderate-to-severe LARS symptoms. Conclusions: In this study, QoL and bowel function improved significantly during the first 6 months after colorectal cancer surgery. Although most patients demonstrated recovery, persistent bowel dysfunction and stoma-related challenges remain important issues. These findings highlight the need for comprehensive postoperative care and routine assessment of both QoL and functional outcomes. Full article

Background and aims: Lactiplantibacillus plantarum is a widely studied probiotic species with well-documented benefits for gastrointestinal function and immune modulation. However, probiotic effects are strain-specific, and the safety of newly identified strains must be clinically established. L. plantarum K014, isolated from traditionally fermented vegetables, has not previously been evaluated in human subjects. This study aimed to evaluate the safety and tolerability of L. plantarum K014 in healthy Malaysian adults by assessing its effects on anthropometric measures, hematological indices, liver and renal function, gastrointestinal health, and selected immune-related outcomes, including the incidence and severity of common cold symptoms. Methods: This single-center, randomized, double-blind, placebo-controlled trial was conducted over a 6-month period. Of 304 healthy adults screened, 152 were enrolled and randomized in a 1:1 ratio to receive either L. plantarum K014 (≥1 × 10⁹ CFU/day) or placebo (maltodextrin), administered daily in sachet form; 125 participants completed the study. Clinical assessments, including physical examination, anthropometric measurements, and blood analyses, were performed at baseline, Month 4, and Month 6. Gastrointestinal symptoms, stool characteristics, and immune-related outcomes were monitored weekly using structured online questionnaires. Results: L. plantarum K014 was well tolerated, with no probiotic-related adverse events reported. No clinically significant changes were observed in body weight, BMI, hematological indices, or renal function in either group. Exploratory analyses indicated that participants receiving L. plantarum K014 exhibited statistically significant differences in several liver function markers, as well as lower severity of diarrhea and abdominal pain compared with placebo, though these findings were not prespecified efficacy endpoints and should be interpreted cautiously. Similarly, lower weekly ratings of common cold symptoms interfering with work or study were observed in the probiotic group as an exploratory observation. Conclusions: Daily consumption of L. plantarum K014 at a dose of ≥1 × 10⁹ CFU for six months was safe and well tolerated in healthy adults. The absence of adverse effects, together with observed trends toward lower gastrointestinal discomfort and immune-related symptoms, supports the suitability of L. plantarum K014 for further investigation in efficacy-driven clinical studies. Full article

Background: Diarrhea in suckling calves is associated with impaired growth, oxidative stress, immune dysfunction, and intestinal microbial dysbiosis. This study evaluated the effects of compound yeast culture (CYC) supplementation on growth performance, fecal characteristics, antioxidant capacity, immune function, and gut microbiota in diarrheic Holstein calves. Thirty-six approximately 7-day-old calves were enrolled, including 12 healthy calves (CON) and 24 diarrheic calves randomly assigned to a diarrhea group (DIA) or a CYC-supplemented group (DIA-YC; 50 g/d for 30 days). The experimental period lasted 60 days. Results: Compared with the DIA group, calves in the DIA-YC group showed significantly higher average daily feed intake and average daily gain (ADG) during days 31–60 and across the entire period (p < 0.05), with a trend towards increased body weight. Fecal scores were significantly elevated in diarrheic calves during the early and mid-stages but were markedly reduced by CYC supplementation from days 7 to 30; no significant difference was observed between DIA-YC and CON during days 16–30 (p > 0.05). Diarrheic calves exhibited oxidative stress, characterized by decreased total antioxidant capacity (T-AOC) and increased malondialdehyde (MDA). CYC supplementation significantly increased T-AOC, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities, while reducing MDA levels (p < 0.05). Immune analysis showed higher serum IgG and IL-10 levels and lower TNF-α levels in the DIA-YC group, along with improved intestinal barrier indicators, including diamine oxidase (DAO) activity and endotoxin levels. Metagenomic analysis revealed that diarrhea reduced microbial richness and diversity and altered community structure, whereas CYC partially restored microbial diversity and increased beneficial genera such as Prevotella, Coprococcus, Ruminococcus, and Parabacteroides. Functional analysis indicated that CYC enhanced pathways related to immune regulation, energy metabolism, and antioxidant function. Conclusion: CYC supplementation alleviates oxidative stress and immune dysfunction by modulating gut microbiota, thereby improving growth performance and reducing diarrheal severity in calves. Full article

Background: This study investigated the mechanisms underlying diarrhea induced by a high-fat diet (HFD) under a state of fatigue, focusing on gut microbiota dysbiosis, bile acid metabolic disturbance, and gut–liver injury. Methods: Mice were assigned to a normal control diet (NCD) group, a HFD-induced diarrhea under fatigue (HFDM) group, and a HFD-induced diarrhea with aggravated dysbiosis (HFDMA) group. Histopathology, inflammatory factors, intestinal barrier-related proteins, small-intestinal microbiota, and colonic bile acid profiles were assessed, and correlation analyses were performed among gut microbiota, bile acids, and inflammatory factors. Results: Compared with the NCD group, both the HFDM and HFDMA groups showed diarrhea-like and fatigue-like phenotypes, histopathological injury in the small intestine and liver, increased tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, and impaired intestinal barrier function. No significant differences in inflammatory factors were observed between the HFDM and HFDMA groups. Zonula occludens-1 (ZO-1) expression decreased in both model groups but reached statistical significance only in the HFDMA group, whereas Claudin-1 expression was significantly reduced in both groups. Gut microbiota analysis showed altered community structure, with downward trends in alpha diversity that did not reach statistical significance but clear separation trends in beta diversity. Proteobacteria and Streptococcus increased, whereas Ligilactobacillus decreased. Total bile acid levels did not differ significantly among groups; however, the ratio of secondary to primary bile acids was significantly reduced in both model groups, particularly in the HFDMA group, with decreases in representative secondary bile acids, including hyodeoxycholic acid (HDCA) and isolithocholic acid (isoLCA). Correlation analysis further supported close associations among gut microbial alteration, bile acid disturbance, and intestinal and hepatic inflammation. Conclusions: Gut microbiota dysbiosis may disrupt bile acid metabolism, impair intestinal barrier integrity, and promote intestinal and hepatic inflammatory responses, thereby contributing to diarrhea progression under fatigue and HFD conditions through the gut–liver axis. Full article

Antibiotic-associated diarrhea (AAD) is primarily driven by disruption of the gut microbiota accompanied by intestinal mucosal injury. Although multiherb formulations are widely used in East Asian medicine, their collective ecological effects and integrated microbiome–host mechanisms have not been systematically synthesized. This systematic review included 17 preclinical studies that investigated multiherbal formulations in AAD models. Given the substantial heterogeneity in the formulation composition, experimental design, and analytical platforms, a descriptive synthesis was performed. The included formulations were categorized into four clusters based on their shared herbal composition: Qiwei Baizhu San (QWBZP), Lizhong Tang (LZT), Gegen Qinlian Tang (GQT), and other supportive multiherbal formulations. The cluster-based synthesis revealed distinct convergent therapeutic strategies. The QWBZP and LZT clusters primarily supported the restoration of host metabolic and digestive functions, whereas the GQT cluster exhibited potent pathogen control effects with the suppression of opportunistic taxa. Across all clusters, a convergent microbiome–host response emerged, characterized by enrichment of commensal bacteria (e.g., Lactobacillus), upregulation of tight junction proteins (e.g., ZO-1, occludin), and attenuation of pro-inflammatory mediators (e.g., TNF-α, myeloperoxidase). Multiherb formulations in AAD models not only act as microbial modulators but also function as host-directed modulators that stabilize the intestinal homeostatic niche. Botanical interventions may facilitate endogenous microbiome recovery by reinforcing mucosal integrity and reducing environmental resistance. This ecological framework provides a rationale for future translational studies evaluating integrated herbal–probiotic strategies and precise microbiome management for patients with AAD, while further clinical validation is warranted. Full article

Background: Rome IV criteria promote a symptom-based (“positive”) diagnosis of pediatric disorders of gut–brain interaction (DGBIs). In clinical practice, however, organic gastrointestinal diseases may mimic DGBIs and lead to diagnostic revision after further evaluation. We aimed to quantify the diagnostic stability of an initial Rome IV-oriented functional diagnosis in a tertiary pediatric outpatient setting and to identify symptom phenotypes associated with a higher likelihood of later organic reclassification. Methods: We performed a single-center retrospective cohort study (2014–14 May 2021) based on outpatient chart review. Eligible patients were children and adolescents aged 0–18 years with an initial Rome IV-oriented functional diagnosis. Diagnostic reassessment was based on follow-up data, available laboratory and instrumental investigations, and/or response to exclusion therapies. Final diagnoses after reassessment were categorized as functional only, organic, or mixed. Groups were compared using Pearson’s chi-square test. Results: The cohort included 220 males (50.0%) and 220 females (50.0%), with a mean age of 8.86 ± 4.65 years. After reassessment, 343/440 (77.95%) remained functional, 73/440 (16.59%) were reclassified as organic, and 24/440 (5.45%) were classified as mixed. Final diagnosis differed by GI tract involvement (p = 0.001) and by symptom cluster (p = 0.001). Upper GI/dyspepsia-spectrum presentations showed the highest organic yield (27.03%), followed by lower abdominal pain/IBS-spectrum presentations (19.61%). Diarrhea and vomiting/cyclic vomiting each showed 16.67% organic diagnoses (mixed: 10.0% and 7.14%, respectively), whereas constipation showed the greatest diagnostic stability (98.89% functional; 1.11% organic). Functional confirmation rates were similar before and during the pandemic (77.71% vs. 78.70%; p = 0.756). Monthly case volume was higher in 2020–2021 (6.29 vs. 4.61 cases/month). Conclusions: In this tertiary cohort, about one in six children initially diagnosed with a functional disorder were later found to have an organic disease, and an additional 5% had mixed organic–functional presentations. Diagnostic revision was associated with presenting phenotype, with the highest organic yield observed in dyspepsia/upper GI presentations and the lowest in constipation. These findings support symptom-stratified evaluation and follow-up alongside Rome IV criteria. Full article

5-Fluorouracil (5-FU) is a first-line chemotherapeutic agent for solid tumors, but its clinical application is severely limited by dose-dependent intestinal injury that impairs patient quality of life and compromises therapeutic efficacy. Natural polysaccharides, especially marine-derived ones, have become safe and multi-targeted gut-protective candidates due to their excellent biocompatibility and prebiotic-like activities. Larimichthys crocea swim bladder is a characteristic marine biological resource, and its polysaccharides (CIPs) have shown potential bioactivities, yet their protective mechanism against 5-FU-induced intestinal injury remains unclear. Our study explored the protective effects of Larimichthys crocea swim bladder polysaccharides (CIPs) against 5-FU-induced intestinal injury in mice. Following 14-day preventive administration, CIPs alleviated 5-FU-induced body weight loss, diarrhea, colonic shortening, and mucosal injury, and restored goblet cell function. Mechanistically, CIPs enhanced intestinal barrier integrity by upregulating ZO-1, Occludin, and MUC2, suppressed the MyD88/NF-κB pathway to balance inflammatory cytokines, and ameliorated oxidative stress by regulating MDA, GSH, SOD, and CAT. CIPs also restored gut microbial diversity and the Firmicutes/Bacteroidota ratio, and modulated retinol and arginine metabolism. In vitro, CIPs reduced inflammation and oxidative damage in Caco-2 cells and promoted M2 macrophage polarization. Thus, CIPs alleviate 5-FU-induced intestinal injury via multi-targeted regulation of the gut–metabolic axis, showing great potential as a dietary intervention and gut health support agent in food science and oncology nutrition, and boosting the high-value utilization of marine resources. Full article

Weaning impairs intestinal function and growth performance in piglets. This study evaluated a fermented herbal formulation (FHF) composed of five bioactive herbal ingredients—Radix isatidis, Folium isatidis, Radix scutellariae, Fructus forsythiae, and Radix glycyrrhizae—fermented with Enterococcus faecium and Saccharomyces cerevisiae and characterized by flavonoids, phenolic acids, and hydroxylated fatty acids, using the porcine intestinal epithelial cell line (IPEC-J2) and weaned piglets. In vitro, IPEC-J2 cells were pretreated with FHF extract (100–1000 μg/mL) for 3 h prior to lipopolysaccharide (LPS) challenge. In vivo, 72 piglets were weaned at 32 days of age and, after a 3-day post-weaning adaptation period, entered a 35-day feeding trial. The piglets were then randomly assigned to three treatment groups: control (basal diet), A1 (basal diet + 0.4% FHF), and A2 (basal diet + 0.6% FHF during days 1–18, followed by 0.3% FHF during days 19–35). FHF dose-dependently alleviated the LPS-induced decrease in cell viability and suppressed IL-6, IL-8, IL-1β, and TNF-α expression. In piglets, the A2 group showed higher final body weight, average daily gain (ADG), and average daily feed intake (ADFI), lower feed conversion ratio (FCR), and a lower diarrhea rate than the control group. FHF also improved intestinal morphology, reduced serum TNF-α and diamine oxidase (DAO) levels, increased jejunal tight junction protein expression, enriched Limosilactobacillus and Lactobacillus, and elevated acetic and butyric acids. FHF improved intestinal health and growth performance in weaned piglets, with the A2 group showing the best overall efficacy. Full article

Background/Objectives. Diarrhea-predominant irritable bowel syndrome (IBS-D) significantly affects patients’ quality of life (QoL). However, data on disease severity and its correlation with QoL among Vietnamese patients remain limited. This study aimed to investigate the clinical characteristics, symptom severity, and the relationship between symptom burden and quality of life in patients with IBS-D in Vietnam. Methods. A cross-sectional study was conducted on patients diagnosed with IBS-D based on the Rome IV criteria at an outpatient clinic of a tertiary hospital. Disease severity and QoL were assessed using the IBS Symptom Severity Score (IBS-SSS) and the standardized Vietnamese version of the IBS Quality of Life (IBS-QoL) questionnaire, respectively. Clinical characteristics, comorbidities, and overlap syndromes were also recorded. Results. Among the 123 patients enrolled (mean age 42.6 ± 14.5 years; 55.3% female), the median IBS-SSS score was 175 (interquartile range: 140–225), and the median IBS-QoL score was 72 (interquartile range: 54–85). The prevalence of overlap syndromes was relatively high, with functional dyspepsia accounting for 46.3% and gastroesophageal reflux disease for 8.9%. A moderate inverse correlation was observed between IBS-SSS and IBS-QoL scores (r = −0.494; p < 0.001). Notably, patients with severe IBS (IBS-SSS ≥ 300) had significantly higher rates of smoking (44.4% vs. 13.2%; p = 0.012) and diabetes (22.2% vs. 5.3%; p = 0.047) compared to the non-severe group. Conclusions. IBS-D imposes a substantial symptom burden and significantly reduces the quality of life in Vietnamese patients, particularly among those with severe disease. The high prevalence of overlap syndromes, along with contributing factors like smoking and diabetes, further increase the complexity and severity of the condition. Full article

Alpinia oxyphylla Miquel is a perennial medicinal plant widely cultivated in the provinces of Fujian, Guangdong, and Hainan in China. The dried mature fruit of A. oxyphylla, officially recorded as Alpiniae Oxyphyllae Fructus in the pharmacopoeia of the People’s Republic of China (since 2012), is one of the four primary southern medicinal materials in traditional Chinese medicine (TCM). In TCM, the fruit is traditionally used to support kidney function, regulate urination, and alleviate gastrointestinal disorders such as diarrhea. Its continued use across Southeast Asia underscores its enduring ethnopharmacological relevance. The plant is rich in bioactive constituents, including terpenoids, flavonoids, diphenylheptanes, and sterols, which exhibit diverse biological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, and gastrointestinal protective effects. Information on Alpinia oxyphylla was collected from multiple databases, including Web of Science, Google Scholar, PubMed, Baidu Scholar, ScienceDirect, CNKI, and the Pharmacopoeia of the People’s Republic of China. The search strategy included keywords related to A. oxyphylla, its chemical constituents, biological activities, pharmacological effects, traditional medicinal uses, and safety. A bibliometric analysis of 217 English-language publications (2014–2025) using CiteSpace revealed a marked increase in global research interest, with keyword clustering and burst analyses highlighting oxidative stress, Alzheimer’s disease, and cognitive enhancement as emerging research hotspots. Moreover, 692 patents were identified, demonstrating substantial technological innovation related to A. oxyphylla, particularly in essential oil formulations, functional foods, and health-promoting applications. Overall, this review integrates phytochemical, pharmacological, bibliometric, and patent perspectives to provide a holistic understanding of A. oxyphylla and its medicinal fruit, offering a solid scientific foundation for future research, standardization, and translational development. Full article

Solid-state fermentation (SSF) is a long-established biotechnological approach gaining renewed interest for its ability to enhance nutrient availability and improve the functional properties of agro-industrial by-products. This strategy is particularly relevant for early post-weaning piglets, which are highly susceptible to weaning stress due to an immature digestive system and a gut microbiota not yet adapted to solid feed. In this study, the fermentation parameters of flaxseed cake were optimized using a Plackett–Burman experimental design. Protease activity was selected as the response variable due to its relevance for improving protein degradation and potential digestibility in fermented feed ingredients. Accordingly, based on the statistical analysis, the conditions selected for the in vivo trial were 1% molasses, 0.5% yeast extract, 0.05% CaCl₂, 0.5% NaCl, 7.5% inoculum (4.12 × 10⁹ CFU/mL), 60% moisture, and 72 h fermentation. Fermentation time was identified as the main factor positively influencing protease production, while higher CaCl₂ concentrations and inoculum levels negatively affected enzyme activity. Optimization increased protease activity, microbial viability and free amino acid content. In addition, SSF reorganizes the carbohydrate profile by reducing structural fiber fractions, with neutral detergent fiber and acid detergent fiber decreasing by 27% and 29%, respectively, while simultaneously increasing soluble carbohydrates by 14.67%. Phytic acid content being also reduced by 23.81%. A pilot nutritional trial on post-weaned piglets (35 days old) showed that including 8% fermented flaxseed cakes (FFSC group) improved body weight, average daily gain, feed conversion ratio, and diarrhea score, without affecting average daily feed intake, compared with 8% unfermented flaxseed cakes (FSC group). These performance improvements were accompanied by changes in fermentation metabolites and gut microbial composition. Lower isovalerate concentrations suggested reduced proteolysis, while higher propionate levels may contribute to increased blood glucose availability in the FFSC group. These changes coincided with a shift in microbial composition, characterized by a reduced abundance of methanogenic archaea and increased abundances of taxa such as Lactobacillus, Enterococcus, and members of the Lachnospiraceae and Eubacteriaceae families. Full article

Bacillus subtilis is aerobic or facultatively anaerobic. After entering the gastrointestinal tract, its spores germinate and colonize the gut, inhibiting the growth of harmful aerobic bacteria (Escherichia coli, Streptococcus, Staphylococcus aureus). However, it remains unclear whether B. subtilis can inhibit Clostridium perfringens type A infection. In this study, B. subtilis PB6 was added to the diets of pregnant sows infected with Clostridium perfringens type A, which significantly improved the reproductive performance and reduced the incidence of bloat in sows and diarrhea in neonatal piglets. The treatment significantly increased the abundance of intestinal probiotics (B. subtilis, Lactobacillus, Limosilactobacillus reuteri, Lactobacillus johnsonii, Muribaculaceae, Lactobacillus amylovorus, and Lactobacillus reuteri) in sows and decreased the relative abundance of Clostridium perfringens type A after feeding B. subtilis administration. These probiotics can repair the intestinal tissue and improve intestinal histomorphology, and enhance the expression of MUC2 and sIgA in sows, thereby further strengthening the mucosal immune function. B. subtilis can also reduce the levels of inflammatory factors (CRP, IL-1β, and IFN-γ) and attenuate the inflammatory response in sows and neonatal piglets. Taken together, our results suggest that dietary supplementation with B. subtilis PB6 could reduce bloat in sows and diarrhea in piglets while improving intestinal barrier function and microbial balance in sows. Full article

Bovine viral diarrhea virus (BVDV), a globally persistent pathogen, causes bovine viral diarrhea-mucosal disease (BVD-MD), a contagious bovine disease posing significant pressures on both public health and economic development. Baicalin (BA), a flavonoid derived from Scutellaria baicalensis, exhibits broad antiviral activities but suffers from poor aqueous solubility and low bioavailability, limiting its therapeutic potential against BVDV. To address this limitation, we developed BA-loaded poly (ethylene gly-col)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (BA-PEG-PLGA NPs). While autophagy and NLRP3 inflammasome activation have been individually implicated in viral pathogenesis, their functional crosstalk during BVDV infection remains uncharacterized. Herein, we evaluated the antiviral efficacy of BA-PEG-PLGA NPs through integrated in vitro and in vivo experiments. We employed quantitative polymerase chain reaction (qPCR), transcriptome sequencing, Western blot analysis, immunofluorescence microscopy, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms by which BA and BA-PEG-PLGA NPs combat bovine viral diarrhea virus (BVDV) infection. We found that both free BA and BA-PEG-PLGA NPs effectively attenuated BVDV replication in vitro and in vivo; notably, the nano-formulation exhibited superior efficacy. Mechanistically, BA and its nano-formulation restored autophagy homeostasis, suppressed ROS overproduction, and blocked NLRP3 inflammasome activation and pyroptotic cell death effects comparable to the specific NLRP3 inhibitor MCC950. These findings establish the autophagy–NLRP3/pyroptosis axis as a critical pathogenic mechanism in BVDV infection and reveal that nano-formulated baicalin represents an antiviral strategy by coordinately targeting this axis. This work not only provides a translatable nanomedicine approach for BVDV control but also expands the mechanistic understanding of flavonoid-based interventions in viral inflammatory diseases. Full article

Post-weaning diarrhea (PWD) in piglets is a common multifactorial disease in global swine production. Traditional prevention and control strategies relying on high-dose zinc oxide and antibiotics face limitations due to antimicrobial resistance and environmental concerns. This review systematically elucidates the mechanisms of action of plant extracts as alternative interventions against PWD, focusing primarily on categories such as polysaccharides, polyphenols, essential oils, and alkaloids. This review discusses how plant extracts exert their effects through various mechanisms, including improving feed intake, enhancing antioxidant and immune capacities, modulating gut microbiota, repairing intestinal barrier function, and inhibiting pathogens—to alleviate diarrhea induced by weaning stress and pathogenic infections. The findings indicate that plant extracts offer advantages such as multi-target effects, natural origin, and a low propensity for inducing resistance, highlighting their promising potential as alternatives to conventional additives. However, challenges related to compositional complexity, stability, and bioavailability require further investigation and optimization. Full article

Background: Chronic insomnia disorder (CID) frequently coexists with diarrhea-predominant irritable bowel syndrome (IBS-D), a comorbidity characterized by gut–brain axis dysfunction and persistent inflammatory activation. However, the molecular mechanisms underlying this overlap remain incompletely understood, and effective multitarget interventions are lacking. Objectives: This study aimed to identify quercetin as a potential bioactive compound for IBS-D-associated insomnia and to investigate whether its protective effects are associated with modulation of the PI3K/AKT/NF-κB signaling pathway. Methods: CID- and IBS-D-related targets were collected from public databases. Candidate compounds were screened using bioinformatics and network pharmacology analyses, followed by molecular docking. Experimental validation was conducted in 36 male C57BL/6J mice assigned to control, CID+IBS-D model, quercetin-treated, and quercetin-plus-Recilisib-treated groups. Sleep-related behavior, EEG/EMG-derived sleep architecture, intestinal function, inflammatory markers, and pathway-related proteins were assessed. Results: Quercetin was identified as a core candidate compound. Network pharmacology revealed 43 shared targets among CID, IBS-D, and quercetin, with significant enrichment in PI3K/AKT-related signaling. In vivo, quercetin improved sleep-associated phenotypes and intestinal dysfunction; reduced visceral hypersensitivity; restored ZO-1 and Occludin expression; suppressed hypothalamic and colonic inflammatory responses; and was accompanied by reduced phosphorylation of PI3K, AKT, IκB, and NF-κB p65 in the hypothalamus. Quercetin also increased hypothalamic 5-HT1A and GABA_A Rα5 expression. These effects were partially reversed by Recilisib, supporting the involvement of PI3K/AKT-associated signaling in quercetin-mediated protection. Conclusions: Quercetin alleviated key sleep-related and IBS-D-like phenotypes in a composite murine model of gut–sleep comorbidity. The protective effects were associated with reduced inflammatory activation and modulation of PI3K/AKT/NF-κB-related signaling. These findings support quercetin as a promising candidate for gut–brain axis-related comorbid disorders, while further studies are needed to define pathway specificity, tissue exposure, and translational applicability. Full article