Aug 2026· Zhonghua zhong liu za zhi [Chinese journal of oncology]· Vol 48 8, pp.
975-982
· 0 citations
Medicine
TL;DR
Pyridoxic acid suppressed HT-29 cell viability and migration, and correlated positively with several upregulated bacteria, suggesting a microbiota-metabolite axis underlying its anti-tumor effect.
Colon cancer is one of the most common malignant tumors worldwide and is associated with high morbidity and mortality. Conventional treatments are typically administered at advanced stages and often lead to severe adverse effects. Therefore, developing safe and effective nutritional interventions from natural food sources is of great importance for the prevention and management of colon cancer. Dairy-derived protein hydrolysates have received increasing attention as functional food components due to their biological activities and favorable safety profiles. In this study, lactoferrin (LF) was hydrolyzed using alkaline protease to obtain lactoferrin hydrolysate (LFH). LFH was administered to mice with azoxymethane/dextran sulfate sodium-induced colon cancer to evaluate its protective effects. LFH markedly alleviated colonic tissue injury, reduced serum levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, and decreased the expression of tumor markers CEA, CA19-9, as well as the proliferation marker Ki-67, thereby inhibiting tumor progression. At the molecular level, LFH downregulated key genes in the Wnt/β-catenin pathway, including c-Myc, β-catenin, and Cyclin D1. Furthermore, LFH upregulated pro-apoptotic genes Bax, caspase-9, caspase-3, and p53, while downregulating anti-apoptotic genes Bcl-2 and Bcl-xl, suggesting enhanced apoptotic responses in tumor cells. LFH also significantly improved gut microbiota composition by reducing harmful bacteria such as Bacillus, Enterorhabdus, and Odoribacter, while increasing beneficial genera including Ruminococcus and Eubacterium_siraeum_group. Correspondingly, LFH elevated several gut microbial metabolites such as Chrysogine, Agmatine, 5′-Deoxy-5-Fluorocytidine, and Glutamyl-γ-Glutamate. Overall, this study provides new insights into the biological effects of LFH on colon cancer and supports its potential application in the development of LFH-based functional foods.
Unknown authors· Food Science and Human Welln...· 0 citations
Colorectal cancer (CRC) linked to colitis is a major cause of cancer-related deaths, highlighting the need for effective treatment options. This study aimed to investigate the effects of berberine (BRR) on gut microbiota and the endocannabinoid system (ECS) in a mouse model of colitis-associated CRC, which was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Through a combination of animal experiments, microbial sequencing, and biochemical assays, we discovered that BRR significantly inhibited tumor development. This was demonstrated by a dose-dependent increase in body weight and a notable decrease in both the number and size of tumors. Histopathological examinations showed a reduction in aberrant crypt foci and inflammation. Additionally, BRR treatment led to lower levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, while increasing the levels of the anti-inflammatory cytokine IL-10, indicating a modulation of immune responses. Importantly, BRR altered gut microbial communities by promoting beneficial bacteria such as Akkermansia muciniphila, Bacteroides, Lachnoclostridium, Blautia, and Prevotellaceae_UCG-001, while reducing harmful species. We also observed improvements in intestinal barrier integrity, characterized by decreased permeability and lower levels of plasma lipopolysaccharides. Furthermore, BRR restored the expression of cannabinoid receptors CB2 and GPR55, suggesting that the ECS plays a role in mediating its effects. In summary, BRR shows significant promise in alleviating colitis-associated CRC through various mechanisms, including the modulation of gut microbiota, regulation of immune responses, and enhancement of intestinal barrier function. Future studies should aim to validate these findings clinically and further explore the efficacy of BRR in the prevention and treatment of CRC.
Yalan Huang, Junhui Zhang, Huiqing Yu et al.· Molecular Nutrition & Food R...· 0 citations
Introduction Cimicifuga foetida L. is widely applied in the clinical treatment of ulcerative colitis (UC); however, its active components and mechanisms have not been deeply investigated. The objective of this study is to investigate the potential bioactive constituents of C. foetida L. for the treatment of UC, and elucidate its therapeutic mechanism. Methods The crude polysaccharide of C. foetida L. was extracted by hot water and purified by DEAE Sepharose™ Fast Flow column to obtain, and named SM05. The structure was determined by HPLC, FT-IR and SEM. The effect of polysaccharide (SM05) on the mouse UC model and its mechanism of action were investigated using a dextran sodium sulfate (DSS)-induced UC model. Changes in body weight, disease activity index, colon length, organ index, histopathological injury, cytokine expression and intestinal tight junction proteins were measured to evaluate the effect of SM05 on UC. IHC, RT-qPCR, and 16s rDNA sequencing were performed to elucidate the underlying mechanism. Results SM05 is mainly composed of mannose, glucose, galactose, and arabinose. SM05 exerts antioxidant effects by activating the Nrf2/Keap1 pathway, thereby inhibiting the NLRP3-induced pyroptosis pathway. This reduces abnormal intestinal cell death and the secretion of inflammatory cytokines, thus protecting the intestinal barrier and suppressing further inflammation. Additionally, SM05 modulates the gut microbiota structure in mice with ulcerative colitis by reducing pathogenic bacteria (e.g., Bacteroides and Desulfovibrio) that damage the intestinal barrier and increasing the abundance of beneficial bacteria (e.g., Akkermansia and Saccharibacteria), thereby alleviating the progression of ulcerative colitis. Discussion In the preliminary biological assessment, the polysaccharide subfraction SM05 alleviated the symptoms of UC induced by DSS. This effect may be related to the activation of the Nrf2/Keap1 pathway, the inhibition of pyroptosis, and the regulation of the intestinal microbiota.
Qing Luo, Yangyang Xu, Zhihua Li et al.· Frontiers in Pharmacology· 0 citations
BACKGROUND
Gut microbiota dysbiosis is a crucial driver of the initiation and progression of colorectal cancer (CRC), where functional gut microbes and their metabolites play key roles in the microecological regulation of CRC. Currently, the association between Lachnospiraceae and CRC progression, as well as the underlying mechanisms, remains incompletely understood and warrants further investigation.
METHODS
Bioinformatics analysis was performed to explore the co-pathway association between gut microbiota and metabolites in CRC patient samples. In vivo animal models were established to assess the regulatory effects of Lachnospiraceae on CRC tumorigenesis and gut microbiota homeostasis. The anti-CRC activities of Lachnospiraceae and its metabolite malate were investigated using in vitro experiments that measured cell viability, proliferation, apoptosis, and colony formation. Western blotting was performed to detect the expression levels of key proteins in the Wingless/Integrated (Wnt)/β-catenin signaling pathway.
RESULTS
Bioinformatics analysis revealed that malate was significantly downregulated in CRC patients, accompanied by gut microbiota dysbiosis driven predominantly by short-chain fatty acid (SCFA)-related Firmicutes such as Lachnospiraceae and Ruminococcaceae. In vivo, Lachnospiraceae restored gut microbiota homeostasis, reduced tumor number, and decreased tumor load. In vitro, Lachnospiraceae suppressed colorectal tumorigenesis and increased colonic D-malate levels.
CONCLUSION
Lachnospiraceae bacterium biologics abstracts accession-2278 (BAA-2278) is associated with anti-CRC effects in preclinical models, potentially mediated through regulation of gut microbiota homeostasis and inhibition of Wnt/β-catenin signaling via its metabolite malate.
Zejun Fang, Yanyan Hu, Minjing Zhu et al.· Frontiers in Bioscience· 0 citations
ETHNOPHARMACOLOGICAL RELEVANCE
Polyporus umbellatus (Pers.) Fries has been used in traditional Chinese medicine for millennia to "promote water metabolism and eliminate dampness", a pathogenic concept central to metabolic dysfunction-associated steatohepatitis (MASH). Its polysaccharide extract is clinically applied in China for dampness-heat related liver disorders, but its specific bioactive components and mechanisms against MASH remain unknown.
AIM OF THE STUDY
To evaluate the anti-MASH efficacy of the (1,3),(1,6)-β-D-glucan from P. umbellatus (PUP) and determine its mechanisms, focusing on the gut microbiota-bile salt hydrolase (BSH)-bile acid (BA)-farnesoid X receptor (FXR) signaling axis.
MATERIALS AND METHODS
MASH was induced in mice using a methionine-choline-deficient (MCD) diet. Biochemical, histological, 16S rRNA sequencing, targeted BA metabolomics, and molecular assays assessed hepatic injury, steatosis, inflammation, fibrosis, gut microbiota, BA profiles, and FXR signaling. Antibiotic intervention and co-housing verified the causal role of gut microbiota.
RESULTS
PUP reduced serum transaminases, total BAs, and bilirubin, and alleviated hepatic steatosis, inflammation, ballooning, and fibrosis. PUP normalized the Firmicutes/Bacteroidota ratio and enriched BSH-producing genera, notably Alistipes and Lactobacillus, thereby restoring fecal BSH activity. BA profiling showed increased fecal excretion of FXR agonists (DCA, LCA) and reduced hepatic hydrophobic free BAs (Fre-BAs). PUP restored intestinal FXR-FGF15 and hepatic FXR-SHP signaling, suppressed CYP7A1, and re-established BA negative feedback. Antibiotic depletion abolished PUP's effects, while co-housing partially recapitulated its hepatoprotective action.
CONCLUSIONS
PUP alleviates MASH via a gut microbiota-BSH-BA-FXR axis by remodeling the gut microbiota, enhancing BSH-dependent BA metabolism, and restoring physiological FXR feedback signaling. This indirect, safe, and multi-targeted mechanism supports PUP as a promising microbiota-dependent FXR modulator for MASH treatment.
Wei Gao, Jiewen Shi, Lijuan Xie et al.· Journal of Ethnopharmacology· 0 citations
BACKGROUND
Polygonum multiflorum Thunb. (PM) can induce hepatotoxicity, particularly with prolonged use. Traditional processing methods, notably steaming (SPM) and steaming with black bean decoction (PPM), are recognized for their ability to mitigate this toxicity; however, the underlying mechanisms, especially from the gut-liver axis perspective, remain poorly understood.
PURPOSE
This study aims to clarify the mechanism by which processing reduces PM-induced hepatotoxicity, with a particular focus on the regulation of the gut-liver axis.
METHODS
We employed a comprehensive approach integrating histopathological examination, multi-omics analyses (including 16S rRNA sequencing, transcriptomics, and metabolomics), and molecular analysis to investigate the distinct effects of PM, SPM, and PPM in a mouse model.
RESULTS
PM caused significant liver injury, characterized by elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and severe pathological damage. This damage was marked by intestinal barrier disruption (decreased tight junction protein-1 (ZO-1) and occludin), systemic inflammation (elevated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels), and activation of the hepatic nuclear factor-kappa B (NF-κB) pathway. Multi-omics analysis revealed that PM induced severe GM dysbiosis (e.g., reduction in the Lactobacillus and a significant increase in the unclassified_f_Oscillospiraceae), a marked decrease in short-chain fatty acids (SCFAs) (e.g., a 72% reduction in butyrate), and disruption of the hepatic bile acid profile. Notably, the two processed products, particularly PPM, significantly reversed these alterations. Compared to the PM group, PPM treatment reduced serum ALT by 82% and exerted extensive protective effects. It restored beneficial bacteria, increased SCFAs levels, normalized bile acid metabolism, and suppressed the hepatic fibrogenic/NF-κB inflammatory axis. This detoxifying effect may be associated with reduced systemic exposure to toxic stilbene glycosides and anthraquinones in the processed PM groups compared to the PM group.
CONCLUSION
This study suggests that processing, particularly with black bean decoction (PPM), can alleviate PM-induced hepatotoxicity by reshaping the GM, restoring its metabolic products (SCFAs), normalizing bile acid signaling, and downregulating the FXR/NF-κB inflammatory axis within the gut-liver axis. These findings provide a mechanistic basis for the clinical preference for processed PM products and highlight the importance of stringent quality control, while also underscoring that residual risk may persist, particularly in susceptible populations.
Andong Dong, Yaya Bai, Yang Xiao et al.· Journal of Ethnopharmacology· 0 citations