Qin Liu

Betanin, a natural pigment with potent antioxidant properties, suffers from poor stability that limits its food applications. To address this limitation, a green pH-driven method was developed to fabricate tilapia protein isolated (TPI)-chondroitin sulfate (CS) nanoparticles for betanin encapsulation. The influence of CS concentration (2-10 mg/mL) on nanoparticle formation, physicochemical characteristics, and delivery performance was systematically investigated. Optimal nanoparticles were formed at 2 mg/mL CS, exhibiting the smallest particle size (567.26 nm) and the maximum encapsulation efficiency (81.43%). The nanoparticles displayed enhanced thermal and light stability. During simulated gastrointestinal digestion, the nanoparticles protected betanin in gastric fluid and increased its bioavailability by 2.44-fold. The release kinetics of betanin fit Logistic model, with Fickian diffusion as key mechanism. These findings demonstrate that TPI-CS/Bt nanoparticles fabricated via pH-driven method offer an effective and green strategy for stabilizing and delivering betanin, providing new insights into valorization of aquatic proteins for functional food applications.

Despite advances in systemic therapies, metastatic colorectal cancer (mCRC) remains largely incurable, underscoring persistent gaps in our understanding of metastatic progression and therapeutic resistance. Emerging evidence suggests that gut and tumor-associated microbial communities may contribute to metastatic progression by shaping organ-specific niches, disrupting intestinal and vascular barriers, remodeling immune and stromal microenvironments, and altering host–microbial metabolism. This review synthesizes current evidence on the involvement of gut and intratumoral microbial communities in colorectal cancer metastasis, with emphasis on liver, lung, lymphatic, and peritoneal metastatic patterns; microbial translocation and barrier dysfunction; microbiome–tumor microenvironment interactions; and metabolic pathways such as bile acid, short-chain fatty acid, and tryptophan metabolism. Furthermore, distinct microbial signatures have been associated with responses to chemotherapy, radiotherapy, immunotherapy, and targeted therapies, supporting their potential value as candidate biomarkers for treatment stratification and prognosis, particularly when interpreted alongside treatment exposure and longitudinal microbiome dynamics. Finally, we discuss microbiome-targeted interventions as emerging adjunctive strategies that may help modulate treatment response, while emphasizing the need for standardized, longitudinal, and mechanistically validated studies before clinical translation in mCRC.

Traditional polysaccharide extraction suffers from low efficiency and high energy consumption, while deep eutectic solvents (DESs) are promising sustainable solvents. This study used DES ChCl-LA (1:2) with ultrasonic assistance to extract polysaccharides from red alga A.taxiformis. Optimized via single-factor experiments and response surface methodology (350 W, 1:30 g/mL, 75 °C), the yield reached 11.28% ± 0.50% (1.5 times higher than that obtained by water extraction). Structural characterization revealed that the DES extract was an acidic polysaccharide, mainly composed of galactose (89.2%), glucose (4.9%), xylose (4.9%), and glucuronic acid (1.0%), with a weight-average molecular weight of 99.88 kDa. Density functional theory and molecular dynamics simulations showed that ChCl-LA enhanced galactose solubility via stronger hydrogen bonding (−25.33 vs. −5.06 kcal/mol for water). Notably, the immunological activity of the DES-extracted polysaccharide was significantly compromised compared to the water-extracted counterpart (p < 0.05). At a concentration of 0.25 mg/mL, the water-extracted polysaccharide-treated group exhibited a 33.98% higher neutral red phagocytosis rate in macrophages, a nitric oxide (NO) secretion level of 34.14 μmol/L (94.98% higher) compared with the DES-extracted polysaccharide group, as well as significantly higher secretion levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The observed disparity in bioactivity is likely due to the distinct chemical profiles resulting from the two extraction methods, including the significantly reduced molecular weight and potential alterations of sulfation degree, monosaccharide composition, and protein content in the DES-extracted polysaccharide. This mechanistic perspective is supported by the relevant literature on the structure–activity relationships of polysaccharides. This study demonstrates the potential of ChCl-LA and elucidates the complex effects of extraction methods on polysaccharide’s structure and function, thereby informing the high-value utilization of A. taxiformis in functional foods.

Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder frequently accompanied by psychological symptoms. Bacterial microbiota plays a critical role in mediating local and systemic immunity, and alterations in these microbial communities have been linked to IBS. Emerging data indicate that other intestinal organisms, including bacteriophages, are closely interlinked with the bacterial microbiota and their host, yet their collective role remains to be elucidated. Here, we analyze the gut multi-kingdom microbiota of 360 IBS patients from a prospective cohort study in Hong Kong, with participants phenotyped through psychological assessment. Our findings reveal significantly lower intra-community correlations in IBS patients compared to healthy controls and highlight unique taxa patterns associated with IBS and mental disorders. Utilizing multi-omic data alongside machine learning techniques, we successfully predicted psychiatric comorbidities in IBS, achieving an average AUC of 0.78. Notably, gut viruses emerged as significant contributors to our predictive model, indicating a vital role for bacteriophages in the gut microbiome of IBS patients. We found that lysogenic phages in IBS displayed a broader host range, with Bilophia containing the most abundant prophages. Our analysis further indicates that IBS patients with depression exhibited a higher prevalence of viral-encoded auxiliary metabolic genes, specifically those involved in the sulfur metabolic pathway related to ubiquinone biosynthesis. The gut virome is increasingly reported to play an important role in the pathogenesis of many diseases. The study provides a systematic characterization of the drivers of the gut viral community and further expands our knowledge of the distinct interaction of gut viruses with their prokaryotic hosts, which is critical for understanding the viral–bacterial environment in IBS.

The composition of the gut microbiome controls innate and adaptive immunity and has emerged as a key regulator of tumor growth and the success of immune checkpoint blockade (ICB) therapy. However, the underlying mechanisms remain unclear. Pancreatic ductal adenocarcinoma (PDAC) tends to be refractory to therapy, including ICB. We found that the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) enhances anti-tumor immunity to PDAC. Delivery of TMAO given intraperitoneally or via dietary choline supplement to PDAC-bearing mice reduces tumor growth and is associated with an immunostimulatory tumor-associated macrophage (TAM) phenotype and activated effector T cell response in the tumor microenvironment. Mechanistically, TMAO signals through potentiating type-I interferon (IFN) pathway and confers anti-tumor effects in a type-I IFN dependent manner. Notably, delivering TMAO-primed macrophages alone produced similar anti-tumor effects. Combining TMAO with ICB (anti-PD1 and/or anti-Tim3) significantly reduced tumor burden and improved survival beyond TMAO or ICB alone. Finally, the levels of trimethylamine (TMA)-producing bacteria and of CutC gene expression correlate with improved survivorship and response to anti-PD1 in cancer patients. Together, our study identifies the gut microbial metabolite TMAO as an important driver of anti-tumor immunity and lays the groundwork for new therapeutic strategies. Citation Format: Gauri Mirji, Alison Worth, Sajad Bhat, Mohamed Sayed, Toshitha Kannan, Aaron Goldman, Hsin-Yao Tang, Qin Liu, Noam Auslander, Chi Dang, Mohamed Abdel-Mohsen, Andrew Kossenkov, Ben Stanger, Rahul Shinde. A microbiome-produced metabolite drives immunostimulatory macrophages and boosts response to immune checkpoint inhibitors in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C023.