Interaction between four galactans with different structural characteristics and gut microbiota.

Human gut microbiota played a key role in maintaining and regulating host health. Gut microbiota composition could be altered by daily diet and related nutrients. Diet polysaccharide, an important dietary nutrient, was one kind of biological macromolecules linked by the glycosidic bonds. Galactans were widely used in foods due to their gelling, thickening and stabilizing properties. Recently, effects of different galactans on gut microbiota have attracted much attention. This review described the structural characteristics of 4 kinds of galactans, including porphyran, agarose, carrageenan, and arabinogalactan, along with the effects of different galactans on gut microbiota and production of short-chain fatty acids. The ability of gut microbiota to utilize galactans with different structural characteristics and related degradation mechanism were also summarized. All these four galactans could be used by gut Bacteroides. Besides, the porphyran could be utilized by Lactobacillus and Bifidobacterium, while the arabinogalactan could be utilized by Lactobacillus, Bifidobacterium and Roseburia. Four galactans with significant difference in molecular weight/degree of polymerization, glycosidic linkage, esterification, branching and monosaccharide composition required gut microbes which could utilize them have corresponding genes encoding the corresponding enzymes for decomposition. This review could help to understand the relationship between galactans with different structural characteristics and gut microbiota, and provide information for potential use of galactans as functional foods.

In vitro gastrointestinal digestion and fermentation models and their applications in food carbohydrates.

Food nutrients plays a crucial role in human health, especially in gastrointestinal (GI) health. The effect of food nutrients on human health mainly depends on the digestion and fermentation process in the GI tract. In vitro GI digestion and fermentation models had the advantages of reproducibility, simplicity, universality, and could integrally simulate the in vivo conditions to mimic oral, gastric, small intestinal and large intestinal digestive processes. They could not only predict the relationship among material composition, structure and digestive characteristics, but also evaluate the bioavailability of material components and the impact of digestive metabolites on GI health. This review systematicly summarized the current state of the in vitro simulation models, and made detailed descriptions for their applications, advantages and disadvantages, and specially their applications in food carbohydrates. In addition, it also provided the suggestions for the improvement of in vitro models and firstly proposed to establish a set of standardized methods of in vitro dynamic digestion and fermentation conditions for food carbohydrates, which were in order to further evaluate more effects of the nutrients on human health in future.

Gut firmicutes: Relationship with dietary fiber and role in host homeostasis.

Firmicutes and Bacteroidetes are the predominant bacterial phyla colonizing the healthy human gut. Accumulating evidence suggests that dietary fiber plays a crucial role in host health, yet most studies have focused on how the dietary fiber affects health through gut Bacteroides. More recently, gut Firmicutes have been found to possess many genes responsible for fermenting dietary fiber, and could also interact with the intestinal mucosa and thereby contribute to homeostasis. Consequently, the relationship between dietary fiber and Firmicutes is of interest, as well as the role of Firmicutes in host health. In this review, we summarize the current knowledge regarding the molecular mechanism of dietary fiber degradation by gut Firmicutes and explain the communication pathway of the dietary fiber-Firmicutes-host axis, and the beneficial effects of dietary fiber-induced Firmicutes and their metabolites on health. A better understanding of the dialogue sustained by the dietary fiber-Firmicutes axis and the host could provide new insights into probiotic therapy and novel dietary interventions aimed at increasing the abundance of Firmicutes (such as Faecalibacterium, Lactobacillus, and Roseburia) to promote health.

Dietary fiber-induced gut Firmicutes and their metabolites exhibit relevant health-promoting functions.Most of dietary fiber have a great effect on gut Firmicutes.Mechanisms of dietary fiber uptake by gut Firmicutes are outlined.Mechanisms of dietary fiber- gut Firmicutes-host interactions require more investigation for the development of dietary fiber in food production and host health.

Review article: Probiotics, prebiotics and dietary approaches during COVID-19 pandemic.

BACKGROUND: Patients with COVID-19 caused by SARS-CoV-2 exhibit diverse clinical manifestations and severity including enteric involvement. Commensal gut bacteria can contribute to defense against potential pathogens by promoting beneficial immune interactions. Interventions targeting the gut microbiome may have systemic anti-viral effects in SARS-CoV-2 infection. SCOPE AND APPROACH: To summarise alterations of gut microbiota in patients with COVID-19 including impact of specific bacteria on disease severity, discuss current knowledge on the role of probiotics, prebiotics and dietary approaches including vitamin D in preventing and reducing disease susceptibility and review clinical studies using probiotics to target coronavirus. A literature review on SARS-CoV-2, COVID-19, gut microbiome and immunity was undertaken and relevant literature was summarised and critically examined. KEY FINDINGS AND CONCLUSIONS: Integrity of gut microbiome was perturbed in SARS-CoV-2 infections and associated with disease severity. Poor prognosis in SARS-CoV-2 infection was observed in subjects with underlying co-morbidities who had increased gut permeability and reduced gut microbiome diversity. Dietary microbes, including probiotics or selected prebiotics of Chinese origin, had anti-viral effects against other forms of coronavirus, and could positively impact host immune functions during SARS-CoV-2 infection. Numerous studies are investigating the role of probiotics in preventing and reducing susceptibility to SARS-CoV-2 infection in healthcare workers, household contacts and affected patients. An approach to strengthen intestinal barrier and lower pro-inflammatory states by adopting a more diversified diet during COVID-19 pandemic.SARS-CoV-2 infection is associated with immune dysfunction and gut microbiota alterations. Delineating mechanisms of probiotics, prebiotics and diet with anti-SARS-CoV-2 immunity present opportunities for discovery of microbial therapeutics to prevent and treat COVID-19.

Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota.

Diabetes mellitus (DM) and its complications are major public health concerns which strongly influence the quality of humans' life. Modification of gut microbiota has been widely used for the management of diabetes. In this review, the relationship between diabetes and gut microbiota, as well as the effects of different dietary components and traditional Chinese medicine (TCM) on gut microflora are summarized. Dietary compounds and TCM possessing bioactive components (fiber and phytochemicals) first change the composition of gut microbiota (inhibiting pathogens and promoting the beneficial bacteria growth) and then influence the production of their metabolites, which would further modify the intestinal environment through inhibiting the production of detrimental compounds (such as lipopolysaccharide, hydrogen sulfide, indol, etc.). Importantly, metabolites (short chain fatty acids and other bioactive components) fermented/degraded by gut microbiota can target multiple pathways in intestine, liver, pancreas, etc., resulting in the improvement of gut health, glycemic control, lipids profile, insulin resistance and inflammation. Furthermore, understanding the interaction between different dietary components and gut microbiota, as well as underlying mechanisms would help design different diet formula for the management of diabetes. Further researches could focus on the combination of different dietary components for preventing and treating diabetes, based on the principle of "multiple components against multiple targets" from the perspective of gut microbiota.

Tea Polysaccharide Prevents Colitis-Associated Carcinogenesis in Mice by Inhibiting the Proliferation and Invasion of Tumor Cells.

The imbalance between cell proliferation and apoptosis can lead to tumor progression, causing oncogenic transformation, abnormal cell proliferation and cell apoptosis suppression. Tea polysaccharide (TPS) is the major bioactive component in green tea, it has showed antioxidant, antitumor and anti-inflammatory bioactivities. In this study, the chemoprophylaxis effects of TPS on colitis-associated colon carcinogenesis, especially the cell apoptosis activation and inhibition effects on cell proliferation and invasion were analyzed. The azoxymethane/dextran sulfate sodium (AOM/DSS) was used to induce the colorectal carcinogenesis in mice. Results showed that the tumor incidence was reduced in TPS-treated AOM/DSS mice compared to AOM/DSS mice. TUNEL staining and Ki-67 immunohistochemistry staining showed that the TPS treatment increased significantly the cell apoptosis and decreased cell proliferation among AOM/DSS mice. Furthermore, TPS reduced the expression levels of the cell cycle protein cyclin D1, matrix metalloproteinase (MMP)-2, and MMP-9. In addition, in vitro studies showed that TPS, suppressed the proliferation and invasion of the mouse colon cancer cells. Overall, our findings demonstrated that TPS could be a potential agent in the treatment and/or prevention of colon tumor, which promoted the apoptosis and suppressed the proliferation and invasion of the mouse colon cancer cells via arresting cell cycle progression.

Metabolism and health effects of phyto-estrogens.

Phyto-estrogens are plant-derived compounds that can exert various estrogenic and anti-estrogenic effects, and are usually used as a natural alternative to estrogen replacement due to their health benefits, including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Phyto-estrogens are also considered as endocrine disruptors due to their structure similar to human female hormone 17-ß oestradiol. However, the issue of whether phyto-estrogens are beneficial or harmful to human health remains unknown, as this may depend on the dose, form, level and duration of administration of phyto-estrogens, and influence by genetics, metabolism, gut physiology, age, diet, and the health status of individuals. Clarification on this issue is necessary for the sake of their two-side effects on human health and rapidly increasing global consumption of phyto-estrogens. This review mainly includes the metabolism of phyto-estrogens and weighs the evidence for and against the purported health benefits and adverse effects of phyto-estrogens.

Effect of fermentation and sterilization on anthocyanins in blueberry.

BACKGROUND: Blueberry products have various health benefits due to their high content of dietary anthocyanins. The aim of this study was to investigate the impact of fermentation and sterilization on total anthocyanin content, composition and some quality attributes of blueberry puree. The blueberry puree used here was fermented for 40 h at 37 °C by Lactobacillus after sterilization. The method of ultra-performance liquid chromatography-mass spectrometry was optimized for the rapid analysis of anthocyanins. Quality attributes including pH, color, total soluble solids and viscosity were measured. RESULTS: A total of 21 anthocyanins and five anthocyanidins were quantified by ultra-performance liquid chromatography. Fermented blueberry had reduced total anthocyanin content (29%) and levels of individual anthocyanins compared with fresh blueberry. Total anthocyanin content was decreased 46% by sterilization, and different degradation behavior of individual anthocyanin was appeared between fermented and sterilized-fermented blueberry puree. Fermentation and sterilization decreased the total soluble solids and pH and changed color parameters, while minimally influencing viscosity. CONCLUSIONS: The loss of total anthocyanin content by fermentation was related to the unstable structure of blueberry anthocyanins. Anthocyanins are sensitive to temperature (>80 °C), and degradation of anthocyanins by sterilization in blueberry should be considered in the fermentation procedure. © 2016 Society of Chemical Industry.

Bidirectional Estrogen-Like Effects of Genistein on Murine Experimental Autoimmune Ovarian Disease.

This study was to investigate the bidirectional estrogen-like effects of genistein on murine experimental autoimmune ovarian disease (AOD). Female BALB/c mice were induced by immunization with a peptide from murine zona pellucida. The changes of estrous cycle, ovarian histomorphology were measured, and the levels of serum sex hormone were analyzed using radioimmunoassay. Proliferative responses of the ovary were also determined by immunohistochemistry. Administration of 25 or 45 mg/kg body weight genistein enhanced ovary development with changes in serum sex hormone levels and proliferative responses. Meanwhile, the proportions of growing and mature follicles increased and the incidence of autoimmune oophoritis decreased, which exhibited normal ovarian morphology in administration of 25 or 45 mg/kg body weight genistein, while a lower dose (5 mg/kg body weight genistein) produced the opposite effect. These findings suggest that genistein exerts bidirectional estrogen-like effects on murine experimental AOD, while a high dose (45 mg/kg body weight) of genistein may suppress AOD.

Modulation of cytokine gene expression by selected Lactobacillus isolates in the ileum, caecal tonsils and spleen of Salmonella-challenged broilers.

Probiotics have been used to control Salmonella colonization in the chicken intestine. Recently, we demonstrated that certain selected Lactobacillus isolates were able to reduce Salmonella infection in the chicken spleen and liver as well as down-regulated Salmonella pathogenicity island 1 virulence gene expression in the chicken caecum. To further understand the mechanisms through which Lactobacillus protected chickens from Salmonella infection, the present study has investigated the Lactobacillus isolate(s)-induced host immune response of chickens to Salmonella enterica serovar Typhimurium infection. A thorough examination of cytokine gene expression in the ileum, caecal tonsils, and spleen on days 1 and 3 post-Salmonella infection showed a dynamic spatial and temporal response to Salmonella infection and Lactobacillus treatments. In most instances, it was evident that treatment of chickens with Lactobacillus isolates could significantly attenuate Salmonella-induced changes in the gene expression profile. These included the genes encoding pro-inflammatory cytokines [lipopolysaccharide-induced TNF factor, interleukin (IL)-6, and IL-8], T helper 1 cytokines [IL-12 and interferon (IFN)-γ], and T helper 2 cytokines (IL-4 and IL-10). Another important observation from the present investigation was that the response induced by a combination of Lactobacillus isolates was generally more effective than that induced by a single Lactobacillus isolate. Our results show that administration of certain selected Lactobacillus isolates can effectively modulate Salmonella-induced cytokine gene expression, and thus help reduce Salmonella infection in chickens.

Lipid metabolism regulation by dietary polysaccharides with different structural properties.

Lipid metabolism plays an important role in energy homeostasis maintenance in response to stress. Nowadays, hyperlipidemia-related chronic diseases such as obesity, diabetes, atherosclerosis, and fatty liver pose significant health challenges. Dietary polysaccharides (DPs) have gained attention for their effective lipid-lowering properties. This review examines the multifaceted mechanisms that DPs employ to lower lipid levels in subjects with hyperlipidemia. DPs could directly inhibit lipid intake and absorption, promote lipid excretion, and regulate key enzymes involved in lipid metabolism pathways, including triglyceride and cholesterol anabolism and catabolism, fatty acid oxidation, and bile acid synthesis. Additionally, DPs indirectly improve lipid homeostasis by modulating gut microbiota composition and alleviating oxidative stress. Moreover, the lipid-lowering mechanisms of particular structural DPs (including ß-glucan, pectin, glucomannan, inulin, arabinoxylan, and fucoidan) are summarized. The relationship between the structure and lipid-lowering activity of DPs is also discussed based on current researches. Finally, potential breakthroughs and future directions in the development of DPs in lipid-lowering activity are discussed. The paper could provide a reference for further exploring the mechanism of DPs for lipid regulations and utilizing DPs as lipid-lowering dietary ingredients.

A review: Effects of microbial fermentation on the structure and bioactivity of polysaccharides in plant-based foods.

Fermented plant-based foods that catering to consumers' diverse dietary preferences play an important role in promoting human health. Recent exploration of their nutritional value has sparked increasing interest in the structural and bioactive changes of polysaccharides during fermentation, the essential components of plant-based foods which have been extensively studied for their structures and functional properties. Based on the latest key findings, this review summarized the dominant fermented plant-based foods in the market, the involved microbes and plant polysaccharides, and the corresponding modification in polysaccharides structure. Further microbial utilization of these polysaccharides, influencing factors, and the potential contributions of altered structure to the functions of polysaccharides were collectively illustrated. Moreover, future research trend was proposed, focusing on the directional modification of polysaccharides and exploration of the mechanisms underlying structural changes and enhanced biological activity during fermentation.

In vitro digestion and fermentation characteristics of eight kinds of pulses and suggestions for different populations.

Pulse-based diets are attracting attention for their potential in combating diet-related non-communicable diseases. However, limited research studies have focused on the digestive and fermentative properties of pulses, which are crucial for exerting benefits. Here, we investigated the in vitro digestibility of starch/protein, along with the fermentation characteristics, of eight pulses and their pastes, including white kidney beans, adzuki beans, cowpeas, broad beans, mung beans, chickpeas, white lentils, and yellow peas. The findings indicated that pulse flours and pastes were low GL food (estimated GL < 10) and had a low degree of protein hydrolysis during simulated gastrointestinal digestion. During in vitro fermentation, pulses flours and pastes decreased the fermentation pH, increased the level of short-chain fatty acids (mainly consisting of valeric acid, followed by acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid), and positively modulated the microbiota composition over time, specifically reducing the ratio of Firmicutes to Bacteroidetes. In addition, we found that boiling could affect the in vitro digestion and fermentation characteristics of pulses, possibly depending on their intrinsic nutrient characteristics. This research could provide a comprehensive summary of the nutrient content, digestibility, and fermentation of eight pulses and their pastes. Guided by factor analysis, for different individuals' consumption, pulses, cowpeas, broad beans, white lentils, and white kidney beans were preferred for diabetic individuals, yellow peas and white lentils were preferred for intestinal homeostasis disorders, and white lentils, broad beans, white kidney beans, and cowpeas were suitable for obese individuals, in which white lentils were considered healthier and suggested for healthy adults.

Insoluble/soluble fraction ratio determines effects of dietary fiber on gut microbiota and serum metabolites in healthy mice.

Both soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) play pivotal roles in maintaining gut microbiota homeostasis; whether the effects of the different ratios of IDF and SDF are consistent remains unclear. Consequently, we selected SDFs and IDFs from six representative foods (apple, celery, kale, black fungus, oats, and soybeans) and formulated nine dietary fiber recipes composed of IDF and SDF with a ratio from 1 : 9 to 9 : 1 (NDFR) to compare their impact on microbial effects with healthy mice. We discovered that NDFR treatment decreased the abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes at the phylum level. The α diversity and relative richness of Parabacteroides and Prevotella at the genus level showed an upward trend along with the ratio of IDF increasing, while the relative abundance of Akkermansia at the genus level and the production of acetic acid and propionic acid exhibited an increased trend along with the ratio of SDF increasing. The relative abundance of Parabacteroides and Prevotella in the I9S1DF group (the ratio of IDF and SDF was 9 : 1) was 1.72 times and 5.92 times higher than that in the I1S9DF group (the ratio of IDF and SDF was 1 : 9), respectively. The relative abundance of Akkermansia in the I1S9DF group was 17.18 times higher than that in the I9S1DF group. Moreover, a high ratio of SDF (SDF reaches 60% or more) enriched the glycerophospholipid metabolism pathway; however, a high ratio of IDF (IDF reaches 80% or more) regulated the tricarboxylic acid cycle. These findings are helpful in the development of dietary fiber supplements based on gut microbiota and metabolites.

Bacteroides uniformis degrades ß-glucan to promote Lactobacillus johnsonii improving indole-3-lactic acid levels in alleviating colitis.

BACKGROUND: Intake of dietary fiber is associated with a reduced risk of inflammatory bowel disease. ß-Glucan (BG), a bioactive dietary fiber, has potential health-promoting effects on intestinal functions; however, the underlying mechanism remains unclear. Here, we explore the role of BG in ameliorating colitis by modulating key bacteria and metabolites, confirmed by multiple validation experiments and loss-of-function studies, and reveal a novel bacterial cross-feeding interaction. RESULTS: BG intervention ameliorates colitis and reverses Lactobacillus reduction in colitic mice, and Lactobacillus abundance was significantly negatively correlated with the severity of colitis. It was confirmed by further studies that Lactobacillus johnsonii was the most significantly enriched Lactobacillus spp. Multi-omics analysis revealed that L. johnsonii produced abundant indole-3-lactic acid (ILA) leading to the activation of aryl hydrocarbon receptor (AhR) responsible for the mitigation of colitis. Interestingly, L. johnsonii cannot utilize BG but requires a cross-feeding with Bacteroides uniformis, which degrades BG and produces nicotinamide (NAM) to promote the growth of L. johnsonii. A proof-of-concept study confirmed that BG increases L. johnsonii and B. uniformis abundance and ILA levels in healthy individuals. CONCLUSIONS: These findings demonstrate the mechanism by which BG ameliorates colitis via L. johnsonii-ILA-AhR axis and reveal the important cross-feeding interaction between L. johnsonii and B. uniformis. Video Abstract.

Improved Loading Capacity and Viability of Probiotics Encapsulated in Alginate Hydrogel Beads by In Situ Cultivation Method.

The objective of this research was to encapsulate probiotics by alginate hydrogel beads based on an in situ cultivation method and investigate the influences on the cell loading capacity, surface and internal structure of hydrogel beads and in vitro gastrointestinal digestion property of cells. Hydrogel beads were prepared by extrusion and cultured in MRS broth to allow probiotics to grow inside. Up to 10.34 ± 0.02 Log CFU/g of viable cell concentration was obtained after 24 h of in situ cultivation, which broke through the bottleneck of low viable cell counts in the traditional extrusion method. Morphology and rheological analyses showed that the structure of the eventually formed probiotic hydrogel beads can be loosed by the existence of hydrogen bond interaction with water molecules and the internal growth of probiotic microcolonies, while it can be tightened by the acids metabolized by the probiotic bacteria during cultivation. In vitro gastrointestinal digestion analysis showed that great improvement with only 1.09 Log CFU/g of loss in viable cells was found after the entire 6 h of digestion. In conclusion, the current study demonstrated that probiotic microcapsules fabricated by in situ cultivation method have the advantages of both high loading capacity of encapsulated viable cells and good protection during gastrointestinal digestion.

The incorporation of peach gum polysaccharide into soy protein based microparticles improves probiotic bacterial survival during simulated gastrointestinal digestion and storage.

The objective of this research was to investigate the in vitro gastrointestinal digestion and storage properties of Lactobacillus plantarum 550 encapsulated in soy protein isolate (SPI) and peach gum polysaccharide (PG) through spray drying. High survival rates (>8.1 Log CFU/g) were obtained for all encapsulation formulas containing PG. Combination of SPI and PG showed positive effects on both gastric resistance and storage stability of cells. Among the formulas tested, sample of SPI:PG = 3:1 showed the highest survival (7.88 ± 0.12 Log CFU/g), corresponding to the strongest electrostatic interaction between SPI and PG. With PG content increasing, the storage stability of probiotic was also enhanced, as PG could reduce the moisture content within microcapsules as well as scavenge free radicals generated during storage. In conclusion, the current study demonstrates that SPI combined with PG may provide effective protection to cells not only during spray drying, but also during storage and gastrointestinal digestion.

Effects of Lactobacillus casei NCU011054 on immune response and gut microbiota of cyclophosphamide induced immunosuppression mice.

Lactobacillus (L.) casei NCU011054 isolated from infant feces has been proven to be a potential probiotic in vitro. The present study aimed to investigate the effects of L. casei NCU011054 on the immune response and gut microbiota in cyclophosphamide (CP)-induced immunosuppression mice. Results indicated that L. casei NCU011054 could increase the levels of mucin (Muc2) and tight junction proteins (ZO-1, occludin and claudin-1). Moreover, L. casei NCU011054 was found to upregulate TLRs/NF-κB pathway (TLR-2, TLR-4, TLR-6, p65 and NF-κB) and two transcription factors (T-bet and GATA-3) mRNA levels, and enhance the number of CD4+T cells. Th1-related cytokines (IL-12p70, IFN-γ and TNF-α) and Th2-related cytokines (IL-2, IL-4, IL-6 and IL-10) significantly increased after L. casei NCU011054 treatment. More importantly, L. casei NCU011054 increased the ratio of T-bet to GATA-3 and IFN-γ to IL-4. Apart from these, L. casei NCU011054 remodeled gut microbiota and modulated gut metabolites in CP-induced immunosuppressed mice. The correlation analysis showed that Lactobacillus upregulated by L. casei NCU011054 was positively correlated with TLRs/NF-κB pathway, and the ratio of T-bet to GATA-3 and IFN-γ to IL-4. All findings revealed that L. casei NCU011054 could improve intestinal immune dysfunction and modulate Th1/Th2 balance via TLRs/NF-κB pathway in CP-induced immunosuppressed mice.

Effects of boiling and steaming process on dietary fiber components and in vitro fermentation characteristics of 9 kinds of whole grains.

Whole grains (WGs) are considered as the representative sources of dietary fiber (DF). Thermal treatments can change the properties of DF, and potentially affecting the gut microbiota as well as human health. In this study, DF content and in vitro fermentation characteristics of 9 kinds of WGs (highland barley, barley, buckwheat, proso millet, quinoa, sorghum, coix seed, foxtail millet, and oats) after boiling and steaming treatments were compared. It was found that boiling and steaming treatments could both increase DF content in these grains, except for barley and foxtail millet. Processed WGs could regulate beneficial microbial genus, such as Bifidobacterium, Prevotella, Megamona and Megasphaera. Oats, quinoa, highland barley, and buckwheat after boiling treatment can produce more total short-chain fatty acids (SCFAs) than steaming treatment (p < 0.05), while barley, foxtail millet and coix seed showed opposite results. This study can provide data support for the design of WGs diets and the development of WGs products which are beneficial for gut health.

Agrocybe cylindracea fucoglucogalactan induced lysosome-mediated apoptosis of colorectal cancer cell through H3K27ac-regulated cathepsin D.

Inducing lysosomal dysfunction is emerging as a promising means for cancer therapy. Agrocybe cylindracea fucoglucogalactan (ACP) is a bioactive ingredient with anti-tumor activity, while its mechanism remains obscure. Herein, we found that ACP visibly inhibited the proliferation of colorectal cancer cells, and the IC50 value on HCT-116 cells (HT29 cells) was 490 µg/mL (786.4 µg/mL) at 24 h. RNA-seq showed that ACP regulated mitochondria, lysosome and apoptosis-related pathways. Further experiments proved that ACP indeed promoted apoptosis and lysosomal dysfunction of HCT-116 cells. Moreover, ChIP-seq revealed that ACP increased histone-H3-lysine-27 acetylation (H3K27ac) on CTSD (cathepsin D) promoter in HCT-116 cells, thus facilitating the binding of transcription factor EB (TFEB), and resulted in ascension of CTSD expression. Additionally, ACP triggered mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential and increasing pro-apoptotic protein levels. Notably, Pepstatin A (CTSD inhibitor) availably alleviated ACP-induced apoptosis. Taken together, our results indicated that ACP induced lysosome-mitochondria mediated apoptosis via H3K27ac-regulated CTSD in HCT-116 cells. This study indicates that ACP has anti-cancer potential in the treatment of colorectal cancer.