The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host’s immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.     

Specific surface modification of liposomes for gut targeting of food bioactive agents

Liposomes have become a research hotspot in recent years as food delivery systems with attractive properties, including the bilayer structure assembled like the cell membrane, reducing the side-effect and improving environmental stability of cargos, controlling release, extending duration of functional ingredients, and high biodegradable and biocompatible abilities in the body. However, the conventional liposomes lack stability during storage and are weak in targeted absorption in the gastrointestinal track. At present, surface modification has been approved to be an effective platform to shield these barricades and help liposomes deliver the agents safely and effectively to the ideal site. In this review, the gastrointestinal stability of conventional liposomes, cargo release models from liposomes, and the biological fate of the core materials after release were emphasized. Then, the strategies in both physical and chemical perspectives to improve the stability and utilization of liposomes in the gastrointestinal tract, and the emerging approaches for improving gut targeting by specifically modified liposomes and the intestinal receptors relative to liposomes/cargos absorption were highlighted. Last but not the least, the safety, challenges, and opportunities for the improvement of liposomal bioavailability were also discussed to inspire new applications of liposomes as oral carriers.     

动物双歧杆菌乳亚种XLTG11对克林霉素诱导的抗生素相关性腹泻的改善作用

目的：通过克林霉素诱导抗生素相关性腹泻(antibiotic-associated diarrhea,AAD)模型,探究动物双歧杆菌乳亚种XLTG11缓解小鼠AAD的作用。方法：将48只6周龄C57BL/6N雄鼠随机分为4组：对照组、模型组、低剂量组和高剂量组,除对照组外,各组小鼠连续14 d灌胃克林霉素(250 mg/(kg m_b·d))诱导AAD模型,然后低剂量组和高剂量组灌胃不同剂量(0.2 mL,5×10⁶、1×10⁷ CFU)动物双歧杆菌乳亚种XLTG11,测定小鼠体质量增长量、盲肠质量、粪便含水量和粪便稠度,测定结肠肿瘤坏死因子α、白细胞介素6(interleukin 6,IL-6)、IL-1β、IL-10水平,血清脂多糖(lipopolysaccharide,LPS)和D-乳酸质量浓度,测定肠道菌群组成及短链脂肪酸含量,以及肠道屏障和核因子κB(nuclear factor kappa-B,NF-κB)信号通路相关基因表达水平。结果：高剂量动物双歧杆菌乳亚种XLTG11显著提高AAD模型小鼠的体质量增长量和...     

酵母甘露糖蛋白体外发酵及其代谢产物的抗炎活性

通过体外肠道菌群厌氧发酵技术研究酵母甘露糖蛋白（mannoprotein,MP）的益生活性。结果表明,MP可调节肠道菌群结构,在门水平增加了拟杆菌门（Bacteroidetes）的相对丰度,降低了厚壁菌门（Firmicutes）、变形菌门（Proteobacteria）的相对丰度,降低了Firmicutes/Bacteroidetes比值。MP显著提高了发酵液中短链脂肪酸尤其是乙酸和丙酸的含量。MP与菊粉具有相似的益生菌活性,菊粉可促进双歧杆菌属（Bifidobacterium）的增殖,而MP可选择性促进拟杆菌属（Bacteroides）、韦荣球菌属（Veillonella）、Clostridium＿sensu＿srticto、布劳特氏菌属（Blautia）、粪杆菌属（Faecalibacterium）、纺锤链杆属（Fusicatenibacter）和产丁酸球菌属（Butyricicoccus）的生长。脂多糖诱导RAW 264.7巨噬细胞模型结果表明MP对炎症没有显著调节作用（P>0.05）,而其发酵液具有显著抗炎活性,且其活性与菊粉组相似,均优于空白组。因此,MP有望成为通过调...     

PUL-Mediated Plant Cell Wall Polysaccharide Utilization in the Gut Bacteroidetes

Plant cell wall polysaccharides (PCWP) are abundantly present in the food of humans and feed of livestock. Mammalians by themselves cannot degrade PCWP but rather depend on microbes resident in the gut intestine for deconstruction. The dominant Bacteroidetes in the gut microbial community are such bacteria with PCWP-degrading ability. The polysaccharide utilization systems (PUL) responsible for PCWP degradation and utilization are a prominent feature of Bacteroidetes. In recent years, there have been tremendous efforts in elucidating how PULs assist Bacteroidetes to assimilate carbon and acquire energy from PCWP. Here, we will review the PUL-mediated plant cell wall polysaccharides utilization in the gut Bacteroidetes focusing on cellulose, xylan, mannan, and pectin utilization and discuss how the mechanisms can be exploited to modulate the gut microbiota.     

Nanoparticle Conjugation of Ginsenoside Rg3 Inhibits Hepatocellular Carcinoma Development and Metastasis

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe₃O₄ nanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamine‐induced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC‐induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty‐nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor‐dominant metabolomics. NpRg3 administration decreases 3‐indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.     

Food-grade carrageenans and their implications in health and disease

Food additives, often used to guarantee the texture, shelf-life, taste, and appearance of processed foods, have gained widespread attention due to their increased link to the growing incidence of chronic diseases. As one of the most common additives, carrageenans have been used in human diets for hundreds of years. While classified as generally recognized as safe (GRAS) for human consumption, numerous studies since the 1980s have suggested that carrageenans, particularly those with random coil conformations, may have adverse effects on gastrointestinal health, including aggravating intestinal inflammation. While these studies have provided some evidence of adverse effects, the topic is still controversial. Some have suggested that the negative consequence of the consumption of carrageenans may be structure dependent. Furthermore, pre-existing conditions may predispose individuals to varied outcomes of carrageenan intake. In this review, structure–function relationships of various carrageenans in the context of food safety are discussed. We reviewed the molecular mechanisms by which carrageenans exert their biological effects. We summarized the findings associated with carrageenan intake in animal models and clinical trials. Moreover, we examined the interactions between carrageenans and the gut microbiome in the pathogenesis of gastrointestinal disorders. This review argues for personalized guidance on carrageenan intake based on individuals’ health status. Future research efforts that aim to close the knowledge gap on the effect of low-dose and chronic carrageenan intake as well as interactions among food additives should be conducive to the improved safety profile of carrageenans in processed food products.