Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.

Helicobacter pylori infection has been associated with the development of insulin resistance (IR). This study aimed to examine the effect of H. pylori-derived extracellular vesicles (EVs) on IR induction. EVs were derived from two H. pylori strains, and characterised by transmission electron microscopy and dynamic light scattering. Different concentrations of insulin were added to HepG2 cells to induce IR model. HepG2 cells were exposed to various concentrations of H. pylori-derived EVs to assess IR development. The gene expression of IRS1, AKT2, GLUT2, IL-6, SOCS3, c-Jun and miR-140 was examined using RT-qPCR. Glucose uptake analysis revealed insulin at 5 × 10 -7 mol/l and EVs at 50 µg/ml induced IR model in HepG2 cells. H. pylori-derived EVs downregulated the expression level of IRS1, AKT2, and GLUT2, and upregulated IL-6, SOCS3, c-Jun, and miR-140 expression in HepG2 cells. In conclusion, our findings propose a novel mechanism by which H. pylori-derived EVs could potentially induce IR.

Helicobacter pylori (H. pylori) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly Lactobacillus, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting H. pylori-induced inflammation are unclear. In our previous study, Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) demonstrated strong anti-inflammatory effects against H. pylori infection in vivo, but its precise mechanisms were not fully understood. Here, we aimed to investigate how L. plantarum ZJ316 inhibits the inflammatory response to H. pylori infection. Our results demonstrated that L. plantarum ZJ316 effectively reduced the expression of pro-inflammatory cytokines in H. pylori-infected AGS cells. Mechanistically, L. plantarum ZJ316 inhibited the NF-κB signaling pathway by preventing the degradation of IκBα, suppressing p65 phosphorylation, and blocking the nuclear translocation of phosphorylated p65. Treatment with the NF-κB inhibitor BAY 11-7082 further decreased tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-1β (IL-1β) levels, confirming the inhibitory effect of L. plantarum ZJ316 on the NF-κB pathway. In H. pylori-infected mice, oral administration of L. plantarum ZJ316 significantly alleviated inflammatory cell infiltration, reduced TNF-α and pepsinogen II (PGII) levels, and increased interleukin-10 (IL-10) levels in serum. A comparative metagenomic analysis of the gastric microbiota revealed a decrease in Prevotella and Desulfovibrio, alongside an increase in Ligilactobacillus and Akkermansia, supporting the protective effects of L. plantarum ZJ316 and correlating with their decreased inflammatory response. In summary, administration of L. plantarum ZJ316 demonstrated robust anti-inflammatory effects against H. pylori infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, L. plantarum ZJ316 holds promise as a novel functional food for protecting the body against H. pylori infection.

The traditional Chinese herbal formula, Danggui Buxue decoction (DBD), is known for its ability in tonifying Qi and promoting the production of blood. It is extensively utilized in treating menstrual anemia and chronic non-healing ulcers. Whereas the impact of DBD on ulcerative colitis (UC) has not been explored, and its therapeutic mechanisms are not well comprehended.

The research sought to investigate the impacts and mechanisms of DBD on UC through a blend of network pharmacology and experimental confirmation.

A network pharmacology approach was utilized to predict DBD's potential mechanisms of action on UC, which were then validated through experimental studies using a dextran sulfate sodium (DSS)-induced UC mouse model to assess its protective effects on intestinal injury. Western blot analysis was conducted to examine changes in protein expression within the primary pathway affected by DBD.

A total of 27 active chemical components, 265 potential targets, and 5867 UC target genes were identified through screening. Of these, 172 common targets were found between DBD and UC. Additionally, 2359 GO biological process items and 157 KEGG signal pathways were identified through analysis. Molecular docking revealed strong binding ability between the main compounds and target proteins. In the DSS-induced UC mouse model, DBD reduced intestinal inflammation and attenuated colonic pathological damage, which is associated with DBD's inhibition of the PI3K/AKT pathway.

DBD significantly attenuates colonic inflammation and preserves the integrity of the intestinal mucosa. Furthermore, the anti-UC efficacy of DBD is intricately linked to the suppression of the PI3K/AKT pathway.

Secondary bile acids, lithocholic acid and deoxycholic acid (LCA and DCA), are dehydroxylated derivatives of primary bile acids. However, in addition to LCA and DCA the intestinal microbiota produced a variety of poorly characterized metabolites. Allo-LCA, a LCA metabolite, acts as a dual GPBAR1 agonist and RORγt inverse agonist and modulates intestinal immunity, although is not yet known whether allo-LCA exerts regulatory functions outside the intestine. In the present study we have therefore investigated whether administration of allo-LCA, 10 mg/kg/day, to mice administered a high fat/high fructose diet (HFD-F) and carbon tetrachloride (Ccl4), a model for metabolic dysfunction-associated steatohepatitis (MASH), protects from development of liver damage. In vitro allo-LCA functions as GPBAR1 agonist and RORγt inverse agonist and prevents macrophages M1 polarization and Th17 polarization of CD4 cells. In vivo studies, while exposure to a HFD-F/Ccl4 promoted insulin resistance and development of a pro-atherogenic lipid profile and liver steatosis and fibrosis, allo-LCA reversed this pattern by improving insulin sensitivity and liver lipid accumulation. The liver transcriptomic profile demonstrated that allo-LCA reversed the dysregulation of multiple pathways associated with immunological, inflammatory and metabolic signaling. Allo-LCA also restored bile acid homeostasis, reversing HFD/Ccl4-induced shifts in bile acid pool composition and restored adipose tissue histopathology and function by reducing the expression of leptin and resistin, two pro-inflammatory adipokines, and restored a healthier composition of the intestinal microbiota. In conclusion, present results expand on the characterization of entero-hepatic signaling and suggest that allo-LCA, a microbial metabolite, might have therapeutic potential in liver diseases.

Helicobacter pylori is a gram-negative microaerophilic microorganism intricately associated with chronic gastrointestinal disorders and gastric cancer. H. pylori can cause various upper digestive tract diseases, including chronic gastritis, peptic ulcer, gastroesophageal reflux disease, and gastric cancer. The bacterium exhibits a variety of pathogenic mechanisms, including colonization, the expression of virulence factors, and the development of drug resistance. This article presents a comprehensive review of H. pylori pathogenesis, emphasizing recent research advancements concerning the cytotoxin-associated gene A, vacuolating cytotoxin, outer membrane proteins, and other virulence factors. Additionally, it examines the molecular mechanisms underlying drug resistance and evaluates the efficacy of conventional therapeutic approaches. Recently, researchers have attempted novel therapeutic regimens, including probiotics and Chinese medicine-assisted therapies, to enhance therapeutic effects. This article aimed to offer an overview of the academic community's comprehension of H. pylori infection and to highlight the current treatment options.

Nod-like receptor protein 3 (NLRP3) is a member of the leucine-rich repeat-containing protein (NLR) canonical inflammasome family. It regulates the pathophysiology of cancer by facilitating immune responses and apoptotic proteins. Furthermore, it has been observed that chemotherapy activates NLRP3 in human malignancies. The secretion of IL-1β and IL-22 to promote cancer spread may be triggered by NLRP3 activation. Furthermore, earlier studies have exhibited that NLRP3 may cause medication resistance when used in cancer treatments given that cell viability may be regulated by NLRP3 depletion. Additionally, clinical studies have demonstrated correlation between NLRP3 expression, lymphogenesis, and cancer metastasis. Various NLRP3 agonists may cause the EMT process, stimulate IL-1β and Wnt/β-catenin signaling, and alter miRNA function in drug-resistant cells. This review seeks to clarify the possibility involvement of NLRP3-related pathways in the control of cancer cells' resistance to widely used treatment approaches, such as chemotherapy. In the end, an improved perception of the corresponding mechanisms behind NLRP3's tumor-supporting activities will help NLRP3-based treatments advance in the future.

Microorganisms in the gut play a pivotal role in human health, influencing various pathophysiological processes. Certain microorganisms are particularly essential for maintaining intestinal homeostasis, reducing inflammation, supporting nervous system function, and regulating metabolic processes. Short-chain fatty acids (SCFAs) are a subset of fatty acids produced by the gut microbiota (GM) during the fermentation of indigestible polysaccharides. The interaction between GM and SCFAs is inherently bidirectional: the GM not only shapes SCFAs composition and metabolism but SCFAs also modulate microbiota's diversity, stability, growth, proliferation, and metabolism. Recent research has shown that GM and SCFAs communicate through various pathways, mainly involving mechanisms related to inflammation and immune responses, intestinal barrier function, the gut-brain axis, and metabolic regulation. An imbalance in GM and SCFA homeostasis can lead to the development of several chronic diseases, including inflammatory bowel disease, colorectal cancer, systemic lupus erythematosus, Alzheimer's disease, and type 2 diabetes mellitus. This review explores the synergistic interactions between GM and SCFAs, and how these interactions directly or indirectly influence the onset and progression of various diseases through the regulation of the mechanisms mentioned above.

Inflammaging is a process of cellular dysfunction associated with chronic inflammation, which plays a significant role in the onset and progression of liver diseases. Research on its mechanisms has become a hotspot. In viral hepatitis, inflammaging primarily involve oxidative stress, cell apoptosis and necrosis, as well as gut microbiota dysbiosis. In non-alcoholic fatty liver disease, inflammaging is more complex, involving insulin resistance, fat deposition, lipid metabolism disorders, gut microbiota dysbiosis, and abnormalities in NAD+ metabolism. In liver tumors, inflammaging is characterized by weakening of tumor suppressive mechanisms, remodeling of the liver microenvironment, metabolic reprogramming, and enhanced immune evasion. Therapeutic strategies targeting inflammaging have been developing recently, and antioxidant therapy, metabolic disorder improvement, and immunotherapy are emerging as important interventions for liver diseases. This review focuses on the mechanisms of inflammaging in liver diseases, aiming to provide novel insights for the prevention and treatment of liver diseases.

Non-alcoholic fatty liver disease (NAFLD) is a multisystem metabolic disorder, marked by abnormal lipid accumulation and intricate inter-organ interactions, which contribute to systemic metabolic imbalances. NAFLD may progress through several stages, including simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis, and potentially liver cancer. This disease is closely associated with metabolic disorders driven by overnutrition, with key pathological processes including lipid dysregulation, impaired lipid autophagy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and local inflammation. While hepatic lipid metabolism in NAFLD is well-documented, further research into inter-organ communication mechanisms is crucial for a deeper understanding of NAFLD progression. This review delves into intrahepatic networks and tissue-specific signaling mediators involved in NAFLD pathogenesis, emphasizing their impact on distal organs.

Severe liver fibrosis may be accompanied by intestinal barrier damage, such as bacterial peritonitis, suggesting that the role of the gut-liver axis is nonnegligible. Dachengqi decoction (DCQD) was reported to improve bowel movements, but whether DCQD was effective for intestinal damage caused by liver fibrosis remained unclear.

To investigate the role of DCQD in liver fibrosis-related gut vascular barrier (GVB) damage in mice.

DCQD was verified to reduce the imbalance of the intestinal vascular barrier and restore intestinal homeostasis to prove that DCQD acts through the gut-liver axis.

Three graded doses of DCQD were gavaged into the CCL4-induced mice for 12 weeks to evaluate the resistance to liver and intestinal damage. Immunoblotting and primary flow cytometry were used to assess organ damage; PV-1 to indicate gut vascular barrier damage; serum endotoxin, fecal SCFAs, and liver microbiota translocation to examine the gut-liver axis's crosstalk. Network pharmacology and RNA sequencing were used to analyze and verify the signaling pathway of DCQD.

DCQD significantly ameliorated fibrosis and inflammatory response in the CCL4-induced mice, alleviated gut leakage, downregulated PV-1, relieved liver enterobacterial translocation, restored intestinal homeostasis, and reduced infiltration of myeloid cells in the lamina propria. Network pharmacology and RNA sequencing results indicated that DCQD exerted anti-fibrotic and anti-inflammatory effects in the liver through inhibition of the ESR1/NF-κB/TNFα pathway and maintained GVB homeostasis through the FUT2/Wnt/β-Catenin pathway.

DCQD broke the closed-loop damage of the gut-liver axis to improve GVB injury in mice with liver fibrosis.

Type 1 diabetes (T1D) is characterized by an autoimmune-mediated destruction of pancreatic beta cells and a chronic inflammatory state, which may influence the progression of colorectal cancer (CRC) through immune system dysregulation and enhanced tumor immune evasion. This study aims to elucidate the role of p65 in modulating the tumor microenvironment in CRC within the context of T1D and to determine how this modulation affects tumor growth, immune cell infiltration, and the expression of immune evasion molecules such as CEACAM5. NOD mice, which model T1D, were inoculated with MC38 colon carcinoma cells engineered to knock down p65. Tumor growth was monitored, and the tumor microenvironment was analyzed using flow cytometry to assess the infiltration of immune cells. The expression of Ki-67 and CEACAM5 in tumor cells was also evaluated. Additionally, in vitro assays were conducted to study the proliferation and activation of T cells co-cultured with tumor cells. Knockdown of p65 in tumor cells significantly inhibited tumor growth in NOD mice. This was accompanied by an increased infiltration of cytotoxic CD8+ T cells and no significant change in CD4+ or Foxp3 + T regulatory cells within the tumor microenvironment. There was a notable reduction in the expression of Ki-67 and CEACAM5, indicating decreased proliferation and potential immune evasion capabilities of the tumor cells. Our findings demonstrate that the NF-κB p65 subunit plays a crucial role in promoting tumor growth and modulating the immune microenvironment in CRC, particularly in the context of T1D. Knocking down p65 not only reduces tumor progression but also enhances the anti-tumor immune response by decreasing immune evasion mechanisms. These results suggest that targeting the NF-κB pathway may be a viable strategy to improve the efficacy of cancer immunotherapy, especially in patients with autoimmune diseases like T1D. Physical activity enhances the effect of immune checkpoint blockade by inhibiting the intratumoral HIF1-α/CEACAM5 axis.

The purpose of this study was to investigate the relationship between Helicobacter pylori (H. pylori) infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and the histopathological characteristics of these changes.

We performed a detailed histomorphometry and immunohistochemical analysis of a total of 1635 H. pylori-infected gastric mucosal specimens.

Stage-wise features were as follows: Early stage of infection: H. pylori was colonized in the mucous layer, and very few neutrophils were visible in the layer. Gastric surface epithelial cell infection stage: H. pylori specifically and selectively adhered to the cytoplasm of the surface mucous cells, with the presence of a small number of neutrophils, eosinophils, and lymphocytes infiltration, which is termed early immune response. Compensatory mucous neck cell hyperplasia stage: proliferation of stem cells in the deep gastric pit and infiltration of a large number of lymphocytes in the superficial layer of lamina propria were observed, which is termed immune cell mobilization counterinsurgency. Lamina propria lesion stage: excessive upward migration of the proliferative area. Infiltration of a large number of lymphocytes, plasma cells, monocytes, macrophages, and other immune cells was observed in the whole layer of the gastric mucosa, which is termed automatic replication of immune cells. Abnormal proliferative transformation stage: presence of intranuclear milky globular body cells or signet-ring cell-like heterotypic cells at the junction of the gastric pit and the gastric gland, with proliferation of large numbers of immune cells and vacuolar degeneration of immune cells, which is termed the proliferation and degeneration of immune cells. Intraepithelial neoplasia stage: clonal hyperplasia of epithelial cells and immunosuppression.

For controlling the occurrence and development of gastric cancer and effective immune intervention, it is essential to grasp the relationship between H. pylori infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and its histopathological characteristics.

Helicobacter pylori (H. pylori), a globally prevalent pathogen Group I carcinogen, presents a formidable challenge in gastric cancer prevention due to its increasing antimicrobial resistance and strain diversity. This comprehensive review critically analyzes the limitations of conventional antibiotic-based therapies and explores cutting-edge approaches to combat H. pylori infections and associated gastric carcinogenesis. We emphasize the pressing need for innovative therapeutic strategies, with a particular focus on precision medicine and tailored vaccine development. Despite promising advancements in enhancing host immunity, current Helicobacter pylori vaccine clinical trials have yet to achieve long-term efficacy or gain approval regulatory approval. We propose a paradigm-shifting approach leveraging artificial intelligence (AI) to design precision-targeted, multiepitope vaccines tailored to multiple H. pylori subtypes. This AI-driven strategy has the potential to revolutionize antigen selection and optimize vaccine efficacy, addressing the critical need for personalized interventions in H. pylori eradication efforts. By leveraging AI in vaccine design, we propose a revolutionary approach to precision therapy that could significantly reduce H. pylori -associated gastric cancer burden.

Inflammatory bowel disease (IBD) is a chronic immune-inflammatory disease. Gut microbes, intestinal immunity, and gut barrier function play a critical role in IBD. Growing evidence suggests that synbiotic may offer therapeutic benefits for individuals with colitis, suggesting an alternative therapy against colitis. With this in mind, we creatively prepared a new synbiotic combination consisting of a probiotic strain (Limosilactobacillus reuteri) along with one prebiotic chitooligosaccharides (COS). The protective effects of the synbiotic on DSS-induced colitis and the underlying mechanisms were investigated. We demonstrated that the synbiotic ameliorated colitis in mice, as evidenced by a significant remission in body weight loss and colon shortening, and a decreased disease activity index (DAI). Notably, synbiotic reduced the intestinal inflammation and injury by synergistically decreasing inflammatory factors, inhibiting TLR4/Myd88/NF-κB/NLRP3 signaling, preventing macrophage infiltration, and enhancing the integrity of the intestinal barrier. Moreover, synbiotic selectively promoted the growth of beneficial bacteria (e.g., Akkermansia, Lactobacillus) but decreased the pathogenic bacteria (e.g., Helicobacter). BugBase's analysis supported its ameliorated role in reducing pathogenic bacteria. Collectively, our findings revealed the novel synbiotic had a potential to treat colitis, which was associated with its anti-inflammatory and microbiota-balancing properties. This study will contribute to the development of functional synbiotic products for IBD therapy and will provide valuable insights into their mechanisms.

The tumour microenvironment represents a novel frontier in oncological research. Over the past decade, accumulating evidence has underscored the importance of the tumour microenvironment (TME), including tumour cells, stromal cells, immune cells, and various secreted factors, which collectively influence tumour growth, invasion, and responses to therapeutic agents. Immune cells within the TME are now widely acknowledged to play pivotal roles in tumour development and treatment. While some perspectives have posited that immune cells within the TME facilitate tumour progression and confer resistance to therapeutic interventions, contrasting conclusions also exist. Affirmative and negative conclusions appear to be context dependent, and a unified consensus has yet to be reached. The burgeoning body of research on the relationship between the gut microbiota and tumours in recent years has led to a growing understanding. Most studies have indicated that specific components of the gut microbiota, such as unique bacterial communities or specific secretory factors, play diverse roles in regulating immune cells within the TME, thereby influencing the prognosis and outcomes of cancer treatments. A detailed understanding of these factors could provide novel insights into the TME and cancer therapy. In this study, we aimed to synthesise information on the interactions between the gut microbiota and immune cells within the TME, providing an in-depth exploration of the potential guiding implications for future cancer therapies.

Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.

Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics lags behind the bacterium's ability to mutate, studies have been directed toward finding new anti-H. pylori agents while also optimizing current drug functions. Targeting biofilm, repurposing outer membrane vesicles that were initially a virulence factor of the bacteria, phage therapy, probiotics, and the construction of nanoparticles might be able to complement or even be alternatives for H. pylori treatment. This review aims to present reports on various compounds, either new or combined with current antibiotics, and their pathways to counteract H. pylori resistance.

The purpose of this study is to investigate the effects of non-obese MAFLD on the gut microbiota and metabolic pathways caused by high-temperature processed meals. It was decided to divide the eighteen male Sprague-Dawley rats into three groups: the control group, the dry-fried soybeans (DFS) group, and the high-fat diet (HFD) group. Following the passage of twelve weeks, a series of physical, biochemical, histological, and microbiological examinations were carried out. There were distinct pathological abnormalities brought about by each diet. The DFS diet was found to cause the development of fatty liver and to demonstrate strong relationships between components of the gut microbiota, such as Akkermansia and Mucispirillum, and indices of liver health. Diet-induced changes in the gut microbiome have a significant impact on liver pathology in non-obese patients with metabolically altered liver disease (MAFLD), which suggests that dietary interventions that target gut microbiota could be used to manage or prevent the illness.

Inflammation significantly influences the degeneration of dopaminergic neurons in Parkinson's disease (PD), which is potentially intensified by associated gut dysbiosis. The therapeutic potential of probiotics, due to their antioxidant, anti-inflammatory, and gut microbiota modulatory properties, is explored herein as a means to improve gut health and influence the gut-brain-microbiota axis in the context of PD. In this study, we investigated the role and possible mechanism of Bifidobacterium animalis subsp. lactis MH-022 (B. lactis MH-022) supplementation in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Findings demonstrated that B. lactis MH-022 supplementation markedly ameliorated motor deficits, preserved dopaminergic neurons, enhanced the antioxidant capacity, and mitigated inflammation through restoring mitochondrial function. Furthermore, B. lactis MH-022 supplementation significantly altered the gut microbiota composition, augmenting the production of short-chain fatty acids and promoting the proliferation of beneficial bacterial taxa, thereby reinforcing their anti-inflammatory properties. Correlation analyses established strong associations between specific bacterial taxa and improvements in motor function, antioxidant levels, and reductions in inflammation markers. These insights emphasize the therapeutic potential of B. lactis MH-022 in modulating diverse aspects of PD, particularly highlighting its role in reducing inflammation, restoring mitochondrial function, enhancing antioxidant capacity, and reshaping the gut microbiota. This multifaceted approach underscores the probiotic's potential in reducing neuroinflammation and protecting dopaminergic neurons, thus offering a promising avenue for PD treatment.

There is a contradiction in the use of microbiota-therapies, including probiotics, prebiotics, and synbiotics, to improve the condition of patients with nonalcoholic fatty liver disease (NAFLD). The aim of this review was to evaluate the effect of microbiota-therapy on liver injury, inflammation, and lipid levels in individuals with NAFLD.

Using Pubmed, Embase, Cochrane Library, and Web of Science databases were searched for articles on the use of prebiotic, probiotic, or synbiotic for the treatment of patients with NAFLD up to March 2024.

Thirty-four studies involving 12,682 individuals were included. Meta-analysis indicated that probiotic, prebiotic, and synbiotic supplementation significantly improved liver injury (hepatic fibrosis, SMD = -0.31; 95% CI: -0.53, -0.09; aspartate aminotransferase, SMD = -0.35; 95% CI: -0.55, -0.15; alanine aminotransferase, SMD = -0.48; 95% CI: -0.71, -0.25; alkaline phosphatase, SMD = -0.81; 95% CI: -1.55, -0.08), lipid profiles (triglycerides, SMD = -0.22; 95% CI: -0.43, -0.02), and inflammatory factors (high-density lipoprotein, SMD = -0.47; 95% CI: -0.88, -0.06; tumour necrosis factor alpha, SMD = -0.86 95% CI: -1.56, -0.56).

Overall, supplementation with probiotic, prebiotic, or synbiotic had a positive effect on reducing liver enzymes, lipid profiles, and inflammatory cytokines in patients with NAFLD.

This study aims to evaluate the efficacy of Lacticaseibacillus rhamnosus LRa05 supplementation in enhancing Helicobacter pylori (H. pylori) eradication rate and alleviating the gastrointestinal side effects associated with bismuth quadruple therapy.

H. pylori-positive patients were randomized to receive levofloxacin-based bismuth quadruple therapy combined either probiotic LRa05 or a placebo for two weeks, followed by LRa05 (1 × 1010 CFU) or maltodextrin for the next two weeks. H. pylori infection was detected by 13C breath test pre- and post-treatment. Blood and stool samples were collected at week 0 and week 4 for routine and biochemical analysis, and serum inflammatory markers. Gastrointestinal symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS). Intestinal microbiota was analyzed using 16S rRNA sequencing. The research was listed under the Chinese Clinical Trial Registry (ChiCTR2300072220), and written informed consent was obtained from all participants.

The LRa05 group exhibited a trend toward higher H. pylori eradication rates (86.11%) compared to the placebo group (82.86%), though the difference was not statistically significant. Significant reductions in neutrophil count, alanine aminotransferase, aspartate aminotransferase, pepsinogen I, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) (p < 0.05) suggest that LRa05 supplementation may mitigate inflammation, enhance liver function, and potential aid in early cancer prevention. GSRS symptom scores showed that LRa05 alleviated abdominal pain, acid reflux, bloating, and diarrhea, enhancing patient compliance. Furthermore, 16S rRNA sequencing showed that LRa05 countered the antibiotic-induced disruption of gut microbiota diversity, primarily by increasing beneficial bacteria.

Although LRa05 did not significantly improve the success rate of H. pylori eradication therapy, it has the potential to improve liver function and reduced levels of inflammatory markers such as IL-6 and TNF-α in the body, regulating the inflammatory response. In addition, it played a positive role in alleviating the adverse symptoms and gut microbiota disturbances caused by eradication therapy, providing a possible way to improve the overall health of patients and demonstrating promising clinical potential.

http://www.chictr.org.cn, identifier ChiCTR2300072220.

Helicobacter pylori infection has significant epidemiological relevance due to the carcinogenic nature of this bacterium, which is potentially associated with cancer. When detected, it should ideally be eradicated using a treatment that currently involves a combination of gastric acid suppressors and multiple antibiotics. However, this treatment raises questions regarding efficacy and safety profiles in patients with specific comorbidities, including inflammatory bowel diseases (IBD). Eradication therapy for H. pylori includes components associated with adverse gastrointestinal events, such as Clostridioides difficile colitis. This necessitates quantifying this risk through dedicated studies to determine whether this antimicrobial treatment could be significantly associated with IBD relapse or exacerbation of pre-existing IBD, as well as whether it could potentially lead to the de novo onset of IBD. Although the available evidence is reassuring about the safety of eradication therapy in patients with IBD, it is limited, and there are no specific recommendations for this particular situation in the leading international IBD and H. pylori guidelines. Therefore, studies need to evaluate the efficacy and safety profiles of the available antimicrobial regimens for H. pylori eradication in patients with IBD, both in clinical trial settings and in real-life studies.

Neurodegenerative diseases (NDs) are a group of heterogeneous disorders with a high socioeconomic burden. Although pharmacotherapy is currently the principal therapeutic approach for the management of NDs, mounting evidence supports the notion that the protracted application of available drugs would abate their dopaminergic outcomes in the long run. The therapeutic application of microbiome-based modalities has received escalating attention in biomedical works. In-depth investigations of the bidirectional communication between the microbiome in the gut and the brain offer a multitude of targets for the treatment of NDs or maximizing the patient's quality of life. Probiotic administration is a well-known microbial-oriented approach to modulate the gut microbiota and potentially influence the process of neurodegeneration. Of note, there is a strong need for further investigation to map out the mechanistic prospects for the gut-brain axis and the clinical efficacy of probiotics. In this review, we discuss the importance of microbiome modulation and hemostasis via probiotics, prebiotics, postbiotics and synbiotics in ameliorating pathological neurodegenerative events. Also, we meticulously describe the underlying mechanism of action of probiotics and their metabolites on the gut-brain axis in different NDs. We suppose that the present work will provide a functional direction for the use of probiotic-based modalities in promoting current practical treatments for the management of neurodegenerative-related diseases.

Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota.

H. pylori infection is gaining increasing attention, but detailed investigations into its impact on gastric microbiota remain limited. We collected gastric mucosa samples from 47 individuals divided into three groups: 1. Group HP: patients with initial positive H. pylori infection (25 cases); 2. Group ck: H. pylori-negative patients (14 cases); 3. Group DiffHP: patients with refractory H. pylori infection (8 cases). The samples were analyzed using 16S rDNA sequencing and functional prediction with PICRUSt. Group HP showed differences in flora distribution and function compared to Group ck, while Group DiffHP overlapped with Group HP. The abundances of Aeromonas piscicola, Shewanella algae, Vibrio plantisponsor, Aeromonas caviae, Serratia marcescens, Vibrio parahaemolyticus, Microbacterium lacticum, and Prevotella nigrescens were significantly reduced in both Group DiffHP and Group HP compared to Group ck. Vibrio shilonii was reduced only in Group DiffHP compared to Group ck, while Clostridium perfringens and Paracoccus marinus were increased only in Group DiffHP. LEfSe analysis revealed that Clostridium perfringens and Paracoccus marinus were enriched, whereas Vibrio shilonii was reduced in Group DiffHP compared to Group ck at the species level. In individuals with refractory H. pylori infection, the gastric microbiota exhibited enrichment in various human diseases, organic systems, and metabolic pathways (amino acid metabolism, carbohydrate metabolism, transcription, replication and repair, cell cycle pathways, and apoptosis). Patients with multiple failed H. pylori eradication exhibited significant changes in the gastric microbiota. An increase in Clostridium perfringens and Paracoccus marinus and a decrease in Vibrio shilonii appears to be characteristic of refractory H. pylori infection.

In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.

More than half of the world's population are colonized with H. pylori; however, the prevalence varies geographically with the highest incidence in Africa. H. pylori is probably a commensal organism that has been associated with the development of gastritis, ulcers, and gastric cancer. H. pylori alone is most probably not enough for the development of gastric carcinoma, but evidence for its association with the disease is high and has, therefore, been classified by the International Agency for Research on Cancer as a Class 1 carcinogen. Bacteroidetes and Fusobacteria positively coexisted during H. pylori infection along the oral-gut axis. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Therefore, therapy regimens integrated with probiotics may abolish the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient's compliance. The eradication therapy not only affects gut microbiome but also affects the oral microbiome with robust predominance of harmful bacteria. However, there have been reports of a protective role of H. pylori in Barrett's esophagus, esophageal adenocarcinoma, eosinophilic esophagitis, IBD, asthma, and even multiple sclerosis. Therefore, eradication therapy should be carefully considered, and test to treat policy should be tailored to specific communities especially in highly endemic areas. Supplementation of probiotics, prebiotics, herbals, and microbial metabolites to reduce the negative effects of eradication therapy should be considered. After failure of many eradication attempts, the benefits of H. pylori eradication should be carefully balanced against the risk of adverse effects especially in the elderly, persons with frailty, and intolerance to antibiotics.

Glioma exhibits high recurrence rates and poor prognosis. The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in inflammation. There is a lack of research exploring the NLRP3 in glioma.

We used several databases, networks, Western blotting, multiple immunofluorescence staining to analyze the role of NLRP3 in inflammatory tumor microenvironment (TME).

NLRP3 is higher-expression in glioma with a low mutation load. NLRP3 expression is linked to the infiltration of immune cells, chemokines, immunomodulators, and the TME. Signaling pathways, co-expression genes and interacting proteins contribute to the up-regulation of NLRP3. Patients responding to immunotherapy positively tend to have lower NLRP3 expression relating to the overall survival based on nomogram. Sensitivity to molecular medicines is observed in relation to NLRP3.

The NLRP3 inflammasome plays a pivotal role in TME which could serve as a higher predictive value biomarker and therapeutic target for glioma treatment.

Helicobacter pylori has been recognized as a true pathogen, which is associated with various gastroduodenal diseases, and gastric adenocarcinoma. The crosstalk between H. pylori virulence factors and host autophagy remains challenging. H. pylori can produce extracellular vesicles (EVs) that contribute to gastric inflammation and malignancy. Some probiotic strains have been documented to modulate cell autophagy process. This study was aimed to investigate the modulatory effect of cell-free supernatant (CFS) obtained from Lactobacillus gasseri ATCC 33323 on autophagy induced by H. pylori-derived EVs. EVs were isolated from two clinical H. pylori strains (BY-1 and OC824), and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The viability of AGS cells was assessed after exposure to different concentrations of H. pylori EVs, and L. gasseri CFS. Based on MTT assay and Annexin V-FITC/PI staining, 50 μg/ml of H. pylori EVs and 10 % v/v of L. gasseri CFS were used for further cell treatment experiments. Autophagy was examined using acridin orange (AO) staining, RT-qPCR analysis for autophagy mediators (LC3B, ATG5, ATG12, ATG16L1, BECN1, MTOR, and NOD1), and western blotting for LC3B expression. H. pylori EVs were detected to range in size from 50 to 200 nm. EVs of both H. pylori strains and L. gasseri CFS showed no significant effect on cell viability as compared to untreated cells. H. pylori EVs promoted the development of acidic vesicular organelles and the expression of autophagy-related genes (LC3B, ATG5, ATG12, ATG16L1, BECN1, and NOD1), and decreased the expression of MTOR in AGS cells at 12 and 24 h time periods. In addition, the production of LC3B was increased following 12 h of treatment in AGS cells. In contrast, L. gasseri CFS effectively inhibited EVs-induced autophagy, as evidenced by reduced acidic vesicular organelle formation and modulation of autophagy markers. Our study indicated that L. gasseri CFS can effectively suppress H. pylori EV-induced autophagy in AGS cells. Further investigations are required to decipher the mechanism of action L. gasseri CFS and its metabolites on autophagy inhibition induced by H. pylori.

Recent studies have indicated that gut microbiota-mediated oxidative stress is significantly associated with intestinal diseases such as colorectal cancer, ulcerative colitis, and Crohn's disease. The level of reactive oxygen species (ROS) has been reported to increase when the gut microbiota is dysregulated, especially when several gut bacterial metabolites are present. Although healthy gut microbiota plays a vital role in defending against excessive oxidative stress, intestinal disease is significantly influenced by excessive ROS, and this process is controlled by gut microbiota-mediated immunological responses, DNA damage, and intestinal inflammation. In this review, we discuss the relationship between gut microbiota and intestinal disease from an oxidative stress perspective. In addition, we also provide a summary of the most recent therapeutic approaches for preventing or treating intestinal diseases by modifying gut microbiota.

H. pylori eradication therapy leads to significant changes in the gut microbiome, including influence on the gut microbiome's functional potential. Probiotics are one of the most studied potential methods for reducing the microbiota-related consequences of antibiotics. However, the beneficial effects of probiotics are still under discussion. In addition, there are some concerns about the safety of probiotics, emphasizing the need for research of other therapeutic interventions. The aim of our study was to evaluate the influence of butyric acid+inulin supplements on gut microbiota changes (the gut microbiota composition, abundance of metabolic pathways, and gut resistome) caused by H. pylori eradication therapy.

Twenty two H. pylori-positive patients, aged 19 to 64 years, were enrolled in the study and randomized into two treatment groups, as follows: (1) ECAB-14 (n = 11), with esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, per os, for 14 days, and (2), ECAB-Z-14 (n = 11), with esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, and bismuthate tripotassium dicitrate 240 mg, twice daily, along with butyric acid+inulin (Zacofalk), two tablets daily, each containing 250 mg of butyric acid, and 250 mg of inulin, per os, for 14 days. Fecal samples were collected from each subject prior to eradication therapy (time point I), after the end of eradication therapy (time point II), and a month after the end of eradication therapy (time point III). The total DNA from the fecal samples was isolated for whole genome sequencing using the Illumina NextSeq 500 platform. Qualitative and quantitative changes in gut microbiota were assessed, including alpha and beta diversity, functional potential and antibiotic resistance gene profiling.

Gut microbiota alpha diversity significantly decreased compared with the baseline immediately after eradication therapy in both treatment groups (ECAB-14 and ECAB-Z-14). This diversity reached its baseline in the ECAB-Z-14 treatment group a month after the end of eradication therapy. However, in the ECAB-14 treatment arm, a reduction in the Shannon index was observed up to a month after the end of H. pylori eradication therapy. Fewer alterations in the gut microbiota functional potential were observed in the ECAB-Z-14 treatment group. The abundance of genes responsible for the metabolic pathway associated with butyrate production decreased only in the ECAB-14 treatment group. The prevalence of antibiotic-resistant genes in the gut microbiota increased significantly in both treatment groups by the end of treatment. However, more severe alterations were noted in the ECAB-14 treatment group.

H. pylori eradication therapy leads to taxonomic changes, a reduction in the alpha diversity index, and alterations in the functional potential of the gut microbiota and gut resistome. Taking butyric acid+inulin supplements during H. pylori eradication therapy could help maintain the gut microbiota in its initial state and facilitate its recovery after H. pylori eradication.

This study aimed to elucidate the potential causative links between inflammatory biomarkers and gastric cancer risk via a two-sample Mendelian randomization approach. Leveraging genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization analysis. Instrumental variable selection for inflammatory markers - namely, tissue factor, monocyte chemotactic protein-1, E-selectin, interleukin 6 receptor, and fatty acid-binding protein 4 - was informed by SNP data from the IEU database. Strongly associated SNPs served as instrumental variables. We applied a suite of statistical methods, including Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), MR-Egger, and mode-based estimates, to compute the odds ratios (ORs) that articulate the impact of these markers on gastric cancer susceptibility. The IVW method revealed that the interleukin 6 receptor was inversely correlated with gastric cancer progression (OR = 0.86, 95% CI = 0.74-0.99, P = .03), whereas fatty acid-binding protein 4 was found to elevate the risk (OR = 1.21, 95% CI = 1.05-1.39, P = .03). Instrumental variables comprised 5, 4, 7, 2, and 3 SNPs respectively. Convergent findings from WME, MR-Egger, and mode-based analyses corroborated these associations. Sensitivity checks, including heterogeneity, horizontal pleiotropy assessments, and leave-one-out diagnostics, affirmed the robustness and reliability of our instruments across diverse gastric malignancy tissues without substantial bias. Our research suggests that the interleukin 6 receptor potentially mitigates, while fatty acid-binding protein 4 may contribute to the pathogenesis of gastric cancer (GC). Unraveling the intricate biological interplay between inflammation and oncogenesis offers valuable insights for preemptive strategies and therapeutic interventions in gastric malignancy management.

Colonic epithelial damage and dysregulated immune response are crucial factors in the progression and exacerbation of inflammatory bowel disease (IBD). Nanoenabled targeted drug delivery to the inflamed intestinal mucosa has shown promise in inducing and maintaining colitis remission, while minimizing side effects. Inspired by the excellent antioxidative and anti-inflammatory efficacy of naturally derived magnolol (Mag) and gut homeostasis regulation of microbiota-derived butyrate, we developed a pH/redox dual-responsive butyrate-rich polymer nanoparticle (PSBA) as an oral Mag delivery system for combinational therapy of IBD. PSBA showed a high butyrate content of 22% and effectively encapsulated Mag. The Mag-loaded nanoparticles (PSBA@Mag) demonstrated colonic pH and reduction-responsive drug release, ensuring efficient retention and adhesion in the colon of colitis mice. PSBA@Mag not only normalized the level of reactive oxygen species and inflammatory effectors in inflamed colonic mucosa but also restored the epithelial barrier function in both ulcerative colitis and Crohn's disease mouse models. Importantly, PSBA promoted the migration and healing ability of intestinal epithelial cells in vitro and in vivo, sensitizing the therapeutic efficacy of Mag in animal models. Moreover, transcriptomics and metabolism analyses revealed that PSBA@Mag mitigated inflammation by suppressing the production of pro-inflammatory cytokines and chemokines and restoring the lipid metabolism. Additionally, this nanomedicine modulated the gut microbiota by inhibiting pathogenic Proteus and Escherichia-Shigella and promoting the proliferation of beneficial probiotics, including Lachnoclostridium, Lachnospiraceae_NK4A136_group and norank_f_Ruminococcaceae. Overall, our findings highlight the potential of butyrate-functionalized polymethacrylates as versatile and effective nanoplatforms for colonic drug delivery and mucosa repair in combating IBD and other gastrointestinal disorders.

Helicobacter pylori (H. pylori) is a recalcitrant pathogen, which can cause gastric disorders. During the past decades, polypharmacy-based regimens, such as triple and quadruple therapies have been widely used against H. pylori. However, polyantibiotic therapies can disturb the host gastric/gut microbiota and lead to antibiotic resistance. Thus, simpler but more effective approaches should be developed. Here, some recent advances in nanostructured drug delivery systems to treat H. pylori infection are summarized. Also, for the first time, a drug release paradigm is proposed to prevent H. pylori antibiotic resistance along with an IVIVC model in order to connect the drug release profile with a reduction in bacterial colony counts. Then, local delivery systems including mucoadhesive, mucopenetrating, and cytoadhesive nanobiomaterials are discussed in the battle against H. pylori infection. Afterward, engineered delivery platforms including polymer-coated nanoemulsions and polymer-coated nanoliposomes are poposed. These bioinspired platforms can contain an antimicrobial agent enclosed within smart multifunctional nanoformulations. These bioplatforms can prevent the development of antibiotic resistance, as well as specifically killing H. pylori with no or only slight negative effects on the host gastrointestinal microbiota. Finally, the essential checkpoints that should be passed to confirm the potential effectiveness of anti-H. pylori nanosystems are discussed.

The eradication of Helicobacter pylori is an urgent global issue. However, the traditional regimens have several limitations. Thus, we propose the idea of treating bacterial gastric disease with the objective of eliminating gastric pathogenic bacteria and enhancing gastroprotective effects using gastric probiotics. In this study, a total of 12 Lactobacillus strains were isolated from the gastric mucosa of healthy donors. After evaluation using a weight scoring system, Lactobacillus paragasseri strain LPG-9 was identified as the most promising probiotic for gastric disease, with the highest acid-resistance and the best adhesion characteristics. Gastric colonisation, H. pylori inhibition, anti-inflammatory, and gastric homeostasis effects of LPG-9 were confirmed in C57BL/6 mice. Finally, a safety evaluation and whole-genome sequencing were performed. Based on the results of this study, LPG-9 originates from the gastric microbiota and is a promising probiotic for gastric disease, particularly H. pylori-induced gastritis, providing a solution to this global issue.

Naturally derived alkaloids belong to a class of quite significant organic compounds. Coptisine, a benzyl tetrahydroisoquinoline alkaloid, is one of the major bioactive constituents in Coptis chinensis Franch., which is a famous traditional Chinese medicine. C. chinensis possesses many kinds of functions, including the ability to eliminate heat, expel dampness, purge fire, and remove noxious substances. In Asian countries, C. chinensis is traditionally employed to treat carbuncle and furuncle, diabetes, jaundice, stomach and intestinal disorders, red eyes, toothache, and skin disorders. Up to now, there has been plenty of research of coptisine with respect to its pharmacology. Nevertheless, a comprehensive review of coptisine-associated research is urgently needed. This paper was designed to summarize in detail the progress in the research of the pharmacology, pharmacokinetics, safety, and formulation of coptisine. The related studies included in this paper were retrieved from the following academic databases: The Web of Science, PubMed, Google scholar, Elsevier, and CNKI. The cutoff date was January 2023. Coptisine manifests various pharmacological actions, including anticancer, antimetabolic disease, anti-inflammatory disease, and antigastrointestinal disease effects, among others. Based on its pharmacokinetics, the primary metabolic site of coptisine is the liver. Coptisine is poorly absorbed in the gastrointestinal system, and most of it is expelled in the form of its prototype through feces. Regarding safety, coptisine displayed potential hepatotoxicity. Some novel formulations, including the [Formula: see text]-cyclodextrin-based inclusion complex and nanocarriers, could effectively enhance the bioavailability of coptisine. The traditional use of C. chinensis is closely connected with the pharmacological actions of coptisine. Although there are some disadvantages, including poor solubility, low bioavailability, and possible hepatotoxicity, coptisine is still a prospective naturally derived drug candidate, especially in the treatment of tumors as well as metabolic and inflammatory diseases. Further investigation of coptisine is necessary to facilitate the application of coptisine-based drugs in clinical practice.

Gut microbiota dictates the fate of several diseases, including cancer. Most gastric cancers (GC) belong to gastric adenocarcinomas (GAC). Helicobacter pylori colonizes the gastric epithelium and is the causative agent of 75% of all stomach malignancies globally. This bacterium has several virulence factors, including cytotoxin-associated gene A (CagA), vacuolating cytotoxin (VacA), and outer membrane proteins (OMPs), all of which have been linked to the development of gastric cancer. In addition, bacteria such as Escherichia coli, Streptococcus, Clostridium, Haemophilus, Veillonella, Staphylococcus, and Lactobacillus play an important role in the development of gastric cancer. Besides, lactic acid bacteria (LAB) such as Bifidobacterium, Lactobacillus, Lactococcus, and Streptococcus were found in greater abundance in GAC patients. To identify potential diagnostic and therapeutic interventions for GC, it is essential to understand the mechanistic role of H. pylori and other bacteria that contribute to gastric carcinogenesis. Furthermore, understanding bacteria-host interactions and bacteria-induced inflammatory pathways in the host is critical for developing treatment targets for gastric cancer.

Intestinal microbiota and their metabolites are essential for maintaining intestinal health, regulating inflammatory responses, and enhancing the body's immune function. An increasing number of studies have shown that the intestinal microbiota is tightly tied to tumorigenesis and intervention effects. Intermittent fasting (IF) is a method of cyclic dietary restriction that can improve energy metabolism, prolong lifespan, and reduce the progression of various diseases, including tumors. IF can affect the energy metabolism of tumor cells, inhibit tumor cell growth, improve the function of immune cells, and promote an anti-tumor immune response. Interestingly, recent research has further revealed that the intestinal microbiota can be impacted by IF, in particular by changes in microbial composition and metabolism. These findings suggest the complexity of the IF as a promising tumor intervention strategy, which merits further study to better understand and encourage the development of clinical tumor intervention strategies. In this review, we aimed to outline the characteristics of the intestinal microbiota and its mechanisms in different tumors. Of note, we summarized the impact of IF on intestinal microbiota and discussed its potential association with tumor suppressive effects. Finally, we proposed some key scientific issues that need to be addressed and envision relevant research prospects, which might provide a theoretical basis and be helpful for the application of IF and intestinal microbiota as new strategies for clinical interventions in the future.