JING Jinyan, WEN Yi, WANG Ying, LAN Jiaoli, YANG Min
DOI:10.11714/jsysu.med.YX20260028
摘要:ObjectiveTo investigate the effects of different doses of uncooked corn starch (UCCS), type 2 resistant starch, on intestinal mucosal barrier function in mice and to explore the potentional underlying mechanisms.MethodsTwenty C57BL/6 mice were randomly assigned to four groups and fed either a standard diet (control group) or diets supplemented with low (188.8 g/kg), medium (314.8 g/kg), or high (440.6 g/kg) doses of UCCS for 8 weeks. Body weight and disease activity index (DAI) were monitored. At the endpoint, colon length was measured; histopathological changes in were assessed via HE staining. The expression of tight junction proteins (ZO-1, E-cadherin, and Villin) in the colonic mucosa were detected using immunofluorescence. Serum inflammatory cytokines (IL-6, TNF-α, IL-1β, MIP-1α/CCL3) and fecal calprotectin levels were measured by ELISA. Gut microbiota alterations were analyzed via 16S rRNA gene sequencing and PICRUSt2 functional prediction.ResultsCompared with the control group, UCCS intervention across all doses significantly shortened colon length (P=0.000 5) and increased colonic inflammation scores (P=0.013 3). Immunofluorescence revealed a significantly reduction in the expression and co-localization of ZO-1 and Villin in the colonic mucosa (P<0.05). Systemic inflammation was evidenced by significantly elevated serum levels of IL-6 (P=0.006 4), TNF-α (P=0.000 1), IL-1β (P=0.001 4), and MIP-1α/CCL3 (P<0.000 1). Fecal calprotectin levels were also significantly increased during the early phase (weeks 1-2, P<0.05). 16S rRNA sequencing showed that UCCS significantly altered the β-diversity of the gut microbiota (P<0.05), characterized by the enrichment of butyrate-producing Clostridia_UCG-014, and the opportunistic pathogen Desulfovibrio, alongside a decreased abundance of immunomodulatory genera Akkermansia and Dubosiella. PICRUSt2 analysis suggested that UCCS modulated metabolic pathways related to energy metabolism, glutathione metabolism, and sulfur cycling.ConclusionLong-term or high-dose intake of UCCS may disrupt gut microbiota homeostasis and trigger inflammation response, thereby damaging the intestinal mucosal barrier. These findings suggest that the clinical or dietary application of UCCS should be cautioned regarding dose-dependent risks of intestinal injury.
LIU Hang, ZHU Bowen, FAN Wenzhe, LI Jiaping, WU Yanqin
DOI:10.11714/jsysu.med.YX20260040
摘要:ObjectiveTo characterize the features of the gut microbiome and its association with clinical prognosis in patients with intermediate and advanced hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy.MethodsThis retrospective study enrolled patients with intermediate and advanced HCC who received TACE combined with targeted therapy and immunotherapy at the First Affiliated Hospital of Sun Yat-sen University from February 2025 to July 2025. Baseline clinical data and fecal samples were collected from all enrolled patients before the index hospitalization and treatment. Patients were stratified using two independent criteria: ① a good-prognosis group and a poor-prognosis group, based on whether progression-free survival (PFS) reached 6 months; ② a response group and a non-response group, based on tumor response to the first TACE assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Metagenomic sequencing was performed on fecal samples. Bioinformatic analysis was conducted to evaluate the diversity and compositional differences of intestinal bacterial and fungal communities between groups in each stratification, and to screen for prognosis-associated characteristic microbial taxa.ResultsA total of 61 patients met the inclusion criteria. Analysis of α-diversity and β-diversity showed no statistically significant differences in bacterial and fungal diversity between groups under either stratification strategy (P> 0.05). At the bacterial level, Lactobacillus johnsonii (prognosis stratification: P=0.048; response stratification: P=0.043), Bifidobacterium dentium (prognosis stratification: P=0.004; response stratification: P=0.030) and Clostridioides difficile (prognosis stratification: P=0.017; response stratification: P=0.016) were significantly enriched in both the good prognosis group and the response group. At the fungal level, Cryptococcus decaguttatus (P=0.045), Puccinia striiformis (P=0.002), and Kwoniella quercicola (P=0.015) were enriched in the good‑prognosis group; Kwoniella bestiolae (P=0.037) was enriched in the response group; and Akanthomyces muscarius (P=0.024) was enriched in the non-response group. Survival analysis based on the common differential bacterial abundance in both groupings showed a significant correlation between the abundance of Bifidobacterium dentium and patient prognosis.ConclusionDifferences in the gut microbiota are associated with the prognosis of patients with intermediate and advanced HCC treated with TACE combined with targeted therapy and immunotherapy. Bifidobacterium dentium may serve as a potential predictive biomarker for the efficacy of this combination regimen, and represents a potential intervention target to modulate treatment response. Differences in gut fungal communities are also potentially associated with the prognosis of intermediate and advanced HCC patients receiving TACE combined with targeted therapy and immunotherapy.
摘要:The integrity of the intestinal barrier is the basis of physiological function of the intestine, which is essential for maintaining nutrient absorption, antigen exclusion, and immune homeostasis. High-altitude environments are characterized by hypobaric hypoxia and are often complicated by combined stresses such as cold, intense ultraviolet radiation, increased physical exertion, dehydration, and dietary changes. These factors may lead to synergistic dysfunction of the mechanical, chemical, immune, and biological barriers of the intestine, thereby inducing local or systemic inflammatory responses. Current evidence indicates that high-altitude-related intestinal barrier injury is not driven by a single pathway but is co-mediated by multiple factors: aberrant activation of hypoxia-inflammation signaling pathways, including hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-κB (NF-κB); synergistic enhancement of Notch and Wnt/β-catenin signaling pathways leading to goblet cell reduction and insufficient mucin 2 (MUC2) secretion; imbalance of T helper 17/regulatory T cells (Th17/Treg) and activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome; as well as gut microbiota dysbiosis and weakened protective effects of short-chain fatty acids (SCFAs). This article systematically reviews the molecular mechanisms underlying high-altitude-induced intestinal barrier injury, and proposes a multi-mechanism synergistic model under the “adaptation-decompensation” framework on this basis. Combined with scenarios of acute high-altitude exposure, it summarizes the evidence progress and limitations of intervention strategies of ameliorating intestinal barrier injury, aiming to provide a theoretical basis and practical reference for the prevention and intervention of high-altitude-related intestinal injury.
摘要:Chronic excessive alcohol consumption is a major global public health concern that severely endangers human health. Excessive alcohol intake disrupts the functions of multiple organs and systems in the human body through diverse mechanisms. The alcohol-sensitive microbiota-gut-brain axis plays a critical role in maintaining systemic homeostasis, immune maturation, and endocrine metabolism. Chronic excessive alcohol consumption not only alters the composition of the gut microbiota and the levels of its metabolites, but also compromises intestinal barrier integrity, increases intestinal permeability, and allows harmful metabolites to enter the systemic circulation, thereby triggering a variety of diseases including alcohol-related brain injury. Alcohol-related brain injury is one of the most severe consequences of unrecognized or inadequately treated alcohol use disorder (AUD), which can lead to extensive neuronal damage and neurocognitive dysfunction. Although the potential role of the microbiota-gut-brain axis in alcohol-related brain injury has been proposed, the exact underlying mechanisms have not yet been fully elucidated. Therefore, in this review, we systematically analyze the associations among chronic excessive alcohol consumption, the microbiota-gut-brain axis, and alcohol-related brain injury, and explore the potential mechanisms underlying alcohol-induced brain damage via this axis.