Characterization of Various Noncovalent Polyphenol-Starch Complexes and Their Prebiotic Activities during In Vitro Digestion and Fermentation.

This study explores the structural characterization of six noncovalent polyphenol-starch complexes and their prebiotic activities during in vitro digestion and fermentation. Ferulic acid, caffeic acid, gallic acid, isoquercetin, astragalin, and hyperin were complexed with sweet potato starch (SPS). The polyphenols exhibited high binding capacity (>70%) with SPS. A partial release of flavonoids from the complexes was observed via in vitro digestion, while the phenolic acids remained tightly bound. Molecular dynamics (MD) simulation revealed that polyphenols altered the spatial configuration of polysaccharides and intramolecular hydrogen bonds formed. Additionally, polyphenol-SPS complexes exerted inhibitory effects on starch digestion compared to gelatinized SPS, owing to the increase in resistant starch fraction. It revealed that the different complexes stimulated the growth of Lactobacillus rhamnosus and Bifidobacterium bifidum, while inhibiting the growth of Escherichia coli. Moreover, in vitro fermentation experiments revealed that complexes were utilized by the gut microbiota, resulting in the production of short-chain fatty acids and a decrease in pH. In addition, the polyphenol-SPS complexes altered the composition of gut microbiota by promoting the growth of beneficial bacteria and decreasing pathogenic bacteria. Polyphenol-SPS complexes exhibit great potential for use as a prebiotic and exert dual beneficial effects on gut microbiota.

Dietary Supplementation of Inulin Contributes to the Prevention of Estrogen Receptor-Negative Mammary Cancer by Alteration of Gut Microbial Communities and Epigenetic Regulations.

Breast cancer (BC) is among the most frequently diagnosed malignant cancers in women in the United States. Diet and nutrition supplementation are closely related to BC onset and progression, and inulin is commercially available as a health supplement to improve gut health. However, little is known with respect to inulin intake for BC prevention. We investigated the effect of an inulin-supplemented diet on the prevention of estrogen receptor-negative mammary carcinoma in a transgenic mouse model. Plasma short-chain fatty acids were measured, the gut microbial composition was analyzed, and the expression of proteins related to cell cycle and epigenetics-related genes was measured. Inulin supplementation greatly inhibited tumor growth and significantly delayed tumor latency. The mice that consumed inulin had a distinct microbiome and higher diversity of gut microbial composition compared to the control. The concentration of propionic acid in plasma was significantly higher in the inulin-supplemented group. The protein expression of epigenetic-modulating histone deacetylase 2 (Hdac2), Hdac8, and DNA methyltransferase 3b decreased. The protein expression of factors related to tumor cell proliferation and survival, such as Akt, phospho-PI3K, and NF-kB, also decreased with inulin administration. Furthermore, sodium propionate showed BC prevention effect in vivo through epigenetic regulations. These studies suggest that modulating microbial composition through inulin consumption may be a promising strategy for BC prevention.

Recent advances in the production of oligogalacturonides and their biological properties.

The human population is becoming old and ageing, which is related to a variety of health issues, such as Alzheimers disease, obesity, diabetes, hypercholesterolemia, and some types of cancers like colorectal cancer. Furthermore, diet is a determining factor in the appearance of some of these diseases due to its direct effect at the systemic level (for instance, increase in glucose and LDL-cholesterol levels in the serum) and its influence on the composition and activity of the gut microbiota. In this context, the use of functional ingredients can be a useful strategy to prevent or even treat (in combination with drugs) some of the above-mentioned pathologies. Among the variety of functional ingredients, prebiotics have received significant attention by the scientific community. Although the already commercialized FOS are the most studied prebiotics, some efforts have been devoted to the search and evaluation of new prebiotic candidates with additional properties. In particular, in the last decade, a variety of in vitro and in vivo assays have been carried out using well isolated and characterized oligogalacturonides, demonstrating that some of them have interesting biological properties, including anticancer, antioxidant, antilipidemic, anti-obesity and anti-inflammatory activities besides prebiotic effects. This work reviews the scientific literature published recently on the production of oligogalacturonides with a special focus on their biological properties.

Human milk oligosaccharides as prebiotics.

Based on its richness in immune-related components such as human milk, human milk oligosaccharides (HMOs), milk proteins, and lipids, breast milk can be considered the first functional food that humans encounter in their lifetime. According to WHO recommendations breast milk has to be the only food in an infant's diet in the first six months of age which is then continued up to two years of age with the suitable complementary foods. Regarding breast milk balanced composition, it is considered as the best food of infants thus many studies have been carried out to determine the benefits of breast milk. Based on numerous studies breast milk have a tendency to reduce the risk of type 2 diabetes, obesity, allergies, celiac disease, necrotizing enterocolitis (NEC), gastrointestinal tract infections and some type of cancers. The benefits of breast milk can be explained by its special combination which includes; macronutrients, micronutrients and bioactive components such as immunoglobulins, hormones, growth factors and oligosaccharides. One of the essential bioactive compounds of breast milk is known as human milk oligosaccharides (HMOs). HMOs are unique, bioactive carbohydrates which are identified as the most significant components of breast milk. Since they have structural complexity and multifunctional properties, they are one of the most wondered components of breast milk. HMOs promote the development of the neonatal intestinal immune, and nervous systems. This article briefly describes the history, complex structure and different functions of HMOs and highlight the importance of maternal diet for HMO biosynthesis.

Physicochemical characteristics and biological activities of soluble dietary fibers isolated from the leaves of different quinoa cultivars.

Quinoa leaf is consumed as a promising value-added vegetable in the diet. Although quinoa leaf is rich in soluble dietary fibers, the knowledge regarding their chemical structures and biological activities is still limited, which astricts their application in the functional food industry. Thus, to improve the precise use and application of soluble dietary fibers (SDFs) isolated from quinoa leaves in the food industry, the physicochemical structures and bioactivities of SDFs isolated from different quinoa leaves were systematically investigated. Results indicated that quinoa leaves were rich in SDFs, ranging from 3.30 % to 4.55 % (w/w). Quinoa SDFs were mainly composed of acidic polysaccharides, such as homogalacturonan and rhamnogalacturonan I, which had the molecular weights in the range of 4.228 × 104 -7.059 × 104 Da. Besides, quinoa SDFs exerted potential in vitro antioxidant activities, lipid and bile acid-adsorption capacities, immunoregulatory activities, and prebiotic effects, which might be partially associated with their molecular mass, content of uronic acid, and content of bound polyphenol. Collectively, these findings are beneficial to better understanding the chemical structures and bioactivities of SDFs extracted from different quinoa leaves, which can also provide a scientific basis for developing quinoa SDFs into functional foods in the food industry.

The positive correlation of antioxidant activity and prebiotic effect about oat phenolic compounds.

The correlation of antioxidant activity and prebiotic effect about oat phenolic compounds was invested, while there exists limited studies. Free and bound phenolic compounds were separated from ethyl acetate, n-butanol and aqueous fractions. Fluorescence in situ hybridization was used to investigate gut microbiota of in vitro fermentation samples. The results showed that ethyl acetate fraction possesses higher total phenolics contents than that of aqueous fraction (p < 0.01). The bound-n-butanol and free-ethyl acetate fraction exhibited the higher antioxidant capacity (p < 0.01). The phenolic compounds with more powerful antioxidant capacity could promote the proliferation of gut microbiota (Lactobacillus/Enterococcus spp. and Bifidobacterium spp.) (p < 0.05) and inhibit the growth of gut microbiota (Bacteroides spp. and Clostridium/histolyticum group). There is a positive correlation of antioxidant activity and prebiotic effect about oat phenolic compounds. This study provides a basis for the correlation between antioxidant stress and gut microbiota regulation in vivo.

Fruit by-products as potential prebiotics and promising functional ingredients to produce fermented milk.

Recently, fruit by-products (FBP) have started to be explored due to their prebiotic potential associated with considerable amounts of dietary fibers and polyphenols. These compounds possess anti-inflammatory activity and can reduce dysbiosis, which is characterized by alterations in the composition and function of the gut microbiota and thus may reduce the onset or progression of several diseases. Therefore, the consumption of FBP must be encouraged. Among food products, fermented milk is a potential candidate for carrying FBP. In this scenario, this review discusses the prebiotic potential of FBP and their anti-inflammatory activity and brings a unique contribution, as it highlights fermented milk as a food carrier for FBP. Therefore, the technological application of FBP as a new ingredient to improve the nutritional and functional values of fermented milk, probiotic viability, and the effects of their addition on the physical and sensory characteristics of fermented milk are topics extensively covered in this review. Moreover, we described the chemical composition of FBP, focusing on polysaccharides and bioactive compounds, their obtention methods and potential adverse effects related to their consumption. Finally, limitations and future directions are outlined to deepen the understanding of FBP and to stimulate their use, to prove their prebiotic potential and to optimize their incorporation into fermented milk.

Phytochemical profile, bioactivity and prebiotic potential of bound polyphenols released from Rosa roxburghii fruit pomace dietary fiber during in vitro digestion and fermentation.

The aim of this study was to elucidate the liberation and phytochemical profile of bound polyphenols present in dietary fiber (RPDF) isolated from Rosa roxburghii fruit pomace during in vitro-simulated digestion and colonic fermentation. The variation in the biological activity and prebiotic potential of the released polyphenols from RPDF was investigated. The results showed that the bound polyphenols were released from RPDF at a higher ratio during colonic fermentation than gastrointestinal digestion. The released polyphenols showed antioxidant activity and α-glucosidase inhibitory activity. The in vitro colonic fermentation assay showed that compared with dephenolized RPDF (DP-RPDF), RPDF exhibited a significantly stronger prebiotic effect by lowering the Firmicutes to Bacteroidetes (F/B) ratio at the phylum level, increasing the relative abundances of beneficial bacteria at the genus level, and improving the production of short chain fatty acids (SCFAs). These findings indicate that the bound polyphenols may act as important functional food ingredients that can contribute to the biological properties of RPDF. In addition, this study provides new insights into the high-value utilization of Rosa roxburghii fruit pomace, which will reduce the wastage of resources and greatly contribute to environmental protection.

Bioactive polysaccharides from red seaweed as potent food supplements: a systematic review of their extraction, purification, and biological activities.

Most marine macroalgae such as red seaweeds are potential alternative sources of useful bioactive compounds. Beside serving as food source, recent studies have shown that red seaweeds are rich sources of bioactive polysaccharides. Red seaweed polysaccharides (RSPs) have various physiological and biological activities, which allow them to be used as immunomodulators, anti-obesity agents, and prebiotic ingredients. Lack of summary information and human clinical trials on the various polysaccharides from red seaweeds, however limits industrial-scale utilization of RSPs in functional foods. This review summarizes recent information on the approaches used for RSPs extraction and purification, mechanistic investigations of their biological activities, and related molecular principles behind their purported ability to prevent diseases. The information here also provides a theoretical foundation for further research into the structure and mechanism of action of RSPs and their potential applications in functional foods.

Mucins, gut microbiota, and postbiotics role in colorectal cancer.

An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host and gut microbiota via different dietary patterns (prebiotics and probiotics) is needed to maintain mucus composition, mucin synthesis, and regulation. Here, we review how the interactions between diet and gut microbiota and bacterial metabolites (postbiotics) regulate mucus layer functionalities and mucin expression in human health and disease.

Synbiotic açaí juice (Euterpe oleracea) containing sucralose as noncaloric sweetener: Processing optimization, bioactive compounds, and acceptance during storage.

This study aimed to evaluate the fermentation process of Lacticaseibacillus casei in the açaí juice, and to evaluate the addition of fructooligosaccharides and sucrose. The organic acids, anthocyanins, polyphenolic compounds, and antioxidant activity were also investigated during fermentation. Moreover, the impact of sucrose and sucralose on microbial viability and sensory acceptance of synbiotic products was evaluated during 42 days storage at refrigerated conditions. The conditions for synbiotic juice production were the initial pH of 6.1 and fermentation undertaken at 28 °C for 22 hr. During fermentation, the higher viability was obtained when a combination of 40 g/L of FOS+10 g/L of sucrose was used (9.70 ± 0.01 log CFU/mL). The lactic acid increased from 0.82 to 1.29 g/L during the fermentation while citric acid decreased from 1.05 to 0.75 g/L. The cyanidin-3-O-rutinoside, polyphenolic compounds, and antioxidant activity increased. Thus, fermentation improved the functional value of the beverage. The L. casei viability reduced from 9.71 ± 0.04 to 8.90 ± 0.06 log CFU/ mL in the juice with sucrose, and from 9.71 ± 0.04 to 8.71 ± 0.14 log CFU/ mL in the juice with sucralose. Thus, the açaí juice is a viable matrix for the synbiotic food, which allows the viability maintenance during the storage. Regarding sensory acceptance, the internal preference mapping indicated an increase in the color preference with the storage of synbiotic juices. However, the flavor and overall acceptance reduced with storage. Nevertheless, the flavor and overall acceptance of juice with sucralose were better than the juice with sucrose. After 42 days of storage, penalty analysis revealed that beverage with sucrose showed a lack of sweet taste and excess of sour taste. Thus, a high-quality açaí product with viable probiotic microorganism, high anthocyanins, and polyphenolic compounds contents could be obtained, which can be exploited for commercial use. PRACTICAL APPLICATION: Synbiotic açaí juice is a healthier alternative to consuming products containing this fruit. The inclusion of probiotic microorganisms and prebiotic fructooligosaccharides increased bioactive compounds contents during the shelf life of the juice. The sensory evaluation using the internal preference mapping revealed that the juice flavor with sucralose was better accepted than the juice formulated with addition of sucrose.

The Oleaster (Elaeagnus angustifolia): A Comprehensive Review on Its Composition, Ethnobotanical and Prebiotic Values>.

BACKGROUND: Oleaster or Elaeagnus angustifolia is a deciduous plant from Elaegnacea family and is well-known for its remedial applications. OBJECTIVE: This paper presents a comprehensive review of the potential application of Oleaster's flour incorporated in some food products. Emphasis is given to the physicochemical, biochemical, and functional properties of Oleaster's flour. METHODS: A comprehensive search was carried out to find publications on Oleaster's flour and its application as a prebiotic. The results of the related studies were extracted and summarized in this paper. RESULTS: Oleaster's flour as a prebiotic ingredient enhances antioxidants, polyphenols, fiber, flavonoids, Sterols, carbohydrates, and protein content of food products. CONCLUSION: Further advanced investigations on Oleaster and its functional ingredients revealed that these are efficacious and can be applied as a substitute source in pharmacological industries for medical applications.

Nutrition and gut health: the impact of specific dietary components - it's not just five-a-day.

The health benefits of fruit, vegetables and dietary fibre have been promoted for many years. Much of the supporting evidence is circumstantial or even contradictory and mechanisms underlying health benefits of specific foods are poorly understood. Colorectal cancer shows marked geographical differences in incidence, probably linked with diet, and explanations for this require knowledge of the complex interactions between diet, microbiota and the gut epithelium. Dietary fibres can act as prebiotics, encouraging growth of saccharolytic bacteria, but other mechanisms are also important. Some but not all soluble fibres have a 'contrabiotic' effect inhibiting bacterial adherence to the epithelium. This is particularly a property of pectins (galacturonans) whereas dietary fructans, previously regarded as beneficial prebiotics, can have a proinflammatory effect mediated via toxic effects of high butyrate concentrations. This also suggests that ulcerative colitis could in part result from potentially toxic faecal butyrate concentrations in the presence of a damaged mucus layer. Epithelial adherence of lectins, either dietary lectins as found in legumes, or bacterial lectins such as the galactose-binding lectin expressed by colon cancer-associated Fusobacterium nucleatum, may also be important and could be inhibitable by specific dietary glycans. Conversely, emulsifiers in processed foods may increase bacterial translocation and alter the microbiota thus promoting inflammation or cancer. Focusing on one condition is of limited value although in developing public health messages and growing evidence for impacts of dietary components on all-cause mortality is gaining more attention. We are only just starting to understand the complex interactions between food, the microbiota and health.

Characterization of inulin-type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities.

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.

Prebiotic, Probiotic, Antimicrobial, and Functional Food Applications of Bacillus amyloliquefaciens.

Bacillus amyloliquefaciens belongs to the genus Bacillus and family Baciliaceae. It is ubiquitously found in food, plants, animals, soil, and in different environments. In this review, the application of B. amyloliquefaciens in probiotic and prebiotic microbes in fermentation, synthesis, and hydrolysis of food compounds is discussed as well as further insights into its potential application and gaps. B. amyloliquefaciens is also a potential microbe in the synthesis of bioactive compounds including peptides and exopolysaccharides. In addition, it can synthesize antimicrobial compounds (e.g., Fengycin, and Bacillomycin Lb), which makes its novelty in the food sector greater. Moreover, it imparts and improves the functional, sensory, and shelf life of the end products. The hydrolysis of complex compounds including insoluble proteins, carbohydrates, fibers, hemicellulose, and lignans also shows that B. amyloliquefaciens is a multifunctional and potential microbe which can be applied in the food industry and in functional food processing.

Prebiotics and Community Composition Influence Gas Production of the Human Gut Microbiota.

Prebiotics confer benefits to human health, often by promoting the growth of gut bacteria that produce metabolites valuable to the human body, such as short-chain fatty acids (SCFAs). While prebiotic selection has strongly focused on maximizing the production of SCFAs, less attention has been paid to gases, a by-product of SCFA production that also has physiological effects on the human body. Here, we investigate how the content and volume of gas production by human gut microbiota are affected by the chemical composition of the prebiotic and the community composition of the microbiota. We first constructed a linear system model based on mass and electron balance and compared the theoretical product ranges of two prebiotics, inulin and pectin. Modeling shows that pectin is more restricted in product space, with less potential for H2 but more potential for CO2 production. An ex vivo experimental system showed pectin degradation produced significantly less H2 than inulin, but CO2 production fell outside the theoretical product range, suggesting fermentation of fecal debris. Microbial community composition also impacted results: methane production was dependent on the presence of Methanobacteria, while interindividual differences in H2 production during inulin degradation were driven by a Lachnospiraceae taxon. Overall, these results suggest that both the chemistry of the prebiotic and the composition of the microbiota are relevant to gas production. Metabolic processes that are relatively prevalent in the microbiome, such as H2 production, will depend more on substrate, while rare metabolisms such as methanogenesis depend more strongly on microbiome composition.IMPORTANCE Prebiotic fermentation in the gut often leads to the coproduction of short-chain fatty acids (SCFAs) and gases. While excess gas production can be a potential problem for those with functional gut disorders, gas production is rarely considered during prebiotic design. In this study, we combined the use of theoretical models and an ex vivo experimental platform to illustrate that both the chemical composition of the prebiotic and the community composition of the human gut microbiota can affect the volume and content of gas production during prebiotic fermentation. Specifically, more prevalent metabolic processes such as hydrogen production were strongly affected by the oxidation state of the probiotic, while rare metabolisms such as methane production were less affected by the chemical nature of the substrate and entirely dependent on the presence of Methanobacteria in the microbiota.

Effects of fructans and probiotics on the inhibition of Klebsiella oxytoca and the production of short-chain fatty acids assessed by NMR spectroscopy.

Generally, the selection of fructans prebiotics and probiotics for the formulation of a symbiotic has been based on arbitrary considerations and in vitro tests that fail to take into account competitiveness and other interactions with autochthonous members of the intestinal microbiota. However, such analyzes may be a valuable step in the development of the symbiotic. The present study, therefore, aims to investigate the effect of lactobacilli strains and fructans (prebiotic compounds) on the growth of the intestinal competitor Klebsiella oxytoca, and to assess the correlation with short-chain fatty acids production. The short-chain fatty acids formed in the fermentation of the probiotic/prebiotic combination were investigated using NMR spectroscopy, and the inhibitory activities were assessed by agar diffusion and co-culture methods. The results showed that Lactobacillus strains can inhibit K. oxytoca, and that this antagonism is influenced by the fructans source and probably associated with organic acid production.

Yacón (Smallanthus sonchifolius) prevented inflammation, oxidative stress, and intestinal alterations in an animal model of colorectal carcinogenesis.

BACKGROUND: Yacón (Smallanthus sonchifolius) roots store carbohydrate in the form of prebiotic fructooligosaccharides (FOS), which improve intestinal health. Yacon has the potential to prevent the intestinal barrier alterations associated with colorectal cancer (CRC). This study aimed to investigate the preventive effects of yacón flour (YF) on alterations promoted by CRC induced by 1,2-dimethylhydrazine in rats. RESULTS: CRC increased tumor necrosis factor alpha levels (group CY = 10.2 ± 0.72; group C = 9.6 ± 1.0; group Y = 5.8 ± 0.54; group S = 5.95 ± 0.6 pg mL-1 ) and short-chain fatty acid production, and decreased total antioxidant capacity (group CY = 4.7 ± 0.72; group C = 3.3 ± 0.3; group Y = 4.1 ± 0.47; group S = 6.7 ± 0.78 U mL-1 ). Furthermore, YF treatment reduced intraluminal pH (group CY = 6.45 ± 0.47; group C = 7.65 ± 0.44; group Y = 6.75 ± 0.46; group S = 8.13 ± 0.2), lactulose/mannitol ratio, tumor necrosis factor-alpha (TNF-α)/interleukin (IL)-10 ratio, and increased secretory immunoglobulin A (group CY = 9.48 ± 1.46; group C = 10.95 ± 3.87; group Y = 15.95 ± 7.36; group S = 9.19 ± 1.52), but did not affect IL-10, IL-12, and TNF-α levels nor the IL-12/IL-10 ratio. CONCLUSION: YF as a source of fructooligosaccharides may help to maintain the integrity of intestinal health, which is altered in induced CRC in rats. © 2020 Society of Chemical Industry.

Characterization of chemical composition and prebiotic effect of a dietary medicinal plant Penthorum chinense Pursh.

Penthorum chinense Pursh is a dietary medicinal plant widely distributed in Asia-Pacific countries. The present study aims to profile the chemical constituents of P. chinense and investigate its prebiotic role in modulating gut microbiota. Fifty polyphenolic compounds were rapidly identified using UPLC-HR-MS. Total flavonoid and phenolic contents of P. chinense were 46.6% and 61.3% (w/w), respectively. Thirteen individual polyphenols were quantified, which accounted for 33.1% (w/w). P. chinense induced structural arrangement of microbial community in mice, showing increased microbiota diversity, elevated Bacteroidetes/Firmicutes ratio and enriched gut health-promoting bacteria. After a one-week drug-free wash, most of these changes were recovered, but the abundance of some beneficial bacteria was further increased. The altered composition of gut microbiota enriched several metabolic pathways. Moreover, P. chinense increased antioxidant capacity in vivo. The results suggest that polyphenol-enriched P. chinense modulates gut microbiota and enhances antioxidant capacity in mice toward a beneficial environment for host health.

Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth.

Growing evidence supports the importance of gut microbiota in the control of tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa that promote anti-tumor immunity. Addition of the prebiotics inulin or mucin to the diet of C57BL/6 mice induces anti-tumor immune responses and inhibition of BRAF mutant melanoma growth in a subcutaneously implanted syngeneic mouse model. Mucin fails to inhibit tumor growth in germ-free mice, indicating that the gut microbiota is required for the activation of the anti-tumor immune response. Inulin and mucin drive distinct changes in the microbiota, as inulin, but not mucin, limits tumor growth in syngeneic mouse models of colon cancer and NRAS mutant melanoma and enhances the efficacy of a MEK inhibitor against melanoma while delaying the emergence of drug resistance. We highlight the importance of gut microbiota in anti-tumor immunity and the potential therapeutic role for prebiotics in this process.