Food Bioactive Compounds Research Articles

The Effects of Food Nutrients and Bioactive Compounds on the Gut Microbiota: A Comprehensive Review.

It is now widely recognized that gut microbiota plays a critical role not only in the development and progression of diseases, but also in its susceptibility to dietary patterns, food composition, and nutritional intake. In this comprehensive review, we have compiled the latest findings on the effects of food nutrients and bioactive compounds on the gut microbiota. The research indicates that certain components, such as unsaturated fatty acids, dietary fiber, and protein have a significant impact on the composition of bile salts and short-chain fatty acids through catabolic processes, thereby influencing the gut microbiota. Additionally, these compounds also have an effect on the ratio of Firmicutes to Bacteroides, as well as the abundance of specific species like Akkermansia muciniphila. The gut microbiota has been found to play a role in altering the absorption and metabolism of nutrients, bioactive compounds, and drugs, adding another layer of complexity to the interaction between food and gut microbiota, which often requires long-term adaptation to yield substantial outcomes. In conclusion, understanding the relationship between food compounds and gut microbiota can offer valuable insights into the potential therapeutic applications of food and dietary interventions in various diseases and health conditions.

Rapid identifying of COX-2 inhibitors from turmeric (Curcuma longa) by bioaffinity ultrafiltration coupled with UPLC-Q Exactive-Orbitrap-MS and zebrafish-based in vivo validation

Turmeric (Curcuma longa), a typical source with recognized anti-inflammatory activity, is one such medicine-food homology source, yet its anti-inflammatory mechanisms and specific component combinations remain unclear. In this study, a net fishing method combining bio-affinity ultrafiltration and ultra-high performance liquid chromatography-mass spectrometry (AUF-LC/MS) was employed and 13 potential COX-2 inhibitors were screened out from C. longa. 5 of them (C1, 17, 20, 22, 25) were accurately isolated and identified. Initially, their IC50 values were measured (IC50 of C1, 17, 20, 22 and 25 is 55.08, 48.26, 29.13, 111.28 and 150.48 μM, respectively), and their downregulation of COX-2 under safe concentrations (400, 40, 120, 50 and 400 μM for C1, 17, 20, 22 and 25, respectively) was confirmed on RAW 264.7 cells. Further, in transgenic zebrafish (Danio rerio), significant anti-inflammatory activity at safe concentrations (15, 3, 1.5, 1.5 and 3 μg/mL for C1, 17, 20, 22 and 25, respectively) were observed in a dose-dependent manner. More importantly, molecular docking analysis further revealed the mode of interaction between them and the key active site residues of COX-2. This study screened out and verified unreported COX-2 ligands, potentially accelerating the discovery of new bioactive compounds in other functional foods.

Multi-omic analysis reveals genes and proteins integral to bioactivity of Echinochrome A isolated from the waste stream of the sea urchin industry in Aotearoa New Zealand.

Evechinus chloroticus (commonly known as kina) is a sea urchin species endemic to New Zealand. Its roe is a culinary delicacy to the indigenous Māori and a globally exported food product. Echinochrome A (Ech A) is a bioactive compound isolated from the waste product of kina shells and spines; however, the molecular mechanisms of Ech A bioactivity are not well understood, partly due to Ech A never being studied using unbiased genome-wide analysis. To explore the high-value pharmaceutical potential of kina food waste, we obtained unbiased functional genomic and proteomic profiles of yeast cells treated with Echinochrome A. Abundance was measured for 4100 proteins every 30 min for four hours using fluorescent microscopy, resulting in the identification of 92 proteins with significant alterations in protein abundance caused by Ech A treatment that were over-represented with specific changes in DNA replication, repair and RNA binding after 30 min, followed by specific changes in the metabolism of metal ions (specifically iron and copper) from 60-240 min. Further analysis indicated that Ech A chelated iron, and that iron supplementation negated the growth inhibition caused by Ech A. Via a growth-based genome-wide analysis of 4800 gene deletion strains, 20 gene deletion strains were sensitive to Ech A in an iron-dependent manner. These genes were over-represented in the cellular response to oxidative stress, suggesting that Ech A suppressed growth inhibition caused by oxidative stress. Unexpectedly, genes integral to cardiolipin and inositol phosphate biosynthesis were required for Ech A bioactivity. Overall, these results identify genes, proteins, and cellular processes mediating the bioactivity of Ech A. Moreover, we demonstrate unbiased genomic and proteomic methodology that will be useful for characterizing bioactive compounds in food and food waste.

Probing the binding sites of bioactives with β-Lactoglobulin at different gastrointestinal pHs

Encapsulation is an efficient strategy to preserve the nutritional value of bioactive compounds in functional foods. The whey protein, β-lactoglobulin (βLg), is a potential carrier for bioactives due to its stability over a range of pHs and in the presence of the gastric enzyme, pepsin. In this study, curcumin and folic acid are used as representative hydrophobic and hydrophilic bioactives compounds respectively to investigate the suitability of βLg to encapsulate at different pH conditions of the gastrointestinal tract (2.0, 4.0, and 7.4). Unexpectedly, we found through intrinsic fluorescence spectroscopy that βLg binds both curcumin and folic acid with similar binding affinity at all three pHs. Fourier-transform infrared experiments showed, that with an exception at pH 2.0, H-bonding play a role in the interaction of both bioactives with βLg. Circular dichroism spectroscopy and small angle X-ray scattering showed that the interactions does not alter the structure of the protein. Further, 2D-protein nuclear magnetic resonance spectroscopy demonstrated, that curcumin binds to an external groove at pH 2.65. Whereas at pH 4.0, curcumin was found to bind at the groove and contrary to expectations, also at the calyx (the EF loop was previously thought to close the entrance to the calyx at this pH). At pH 6.5, both curcumin and folic acid bind to βLg at the calyx and the groove. Overall, our study shows that βLg binds curcumin and folic acid at gastrointestinal pHs, suggesting its potential ability to encapsulate both hydrophobic and hydrophilic bioactive molecules in dairy functional foods.

Brown Adipose Tissue, Batokines, and Bioactive Compounds in Foods: An Update.

The discovery of metabolically active brown adipose tissue (BAT) in human adults and the worldwide increase in obesity and obesity-related chronic noncommunicable diseases (NCDs) has made BAT a therapeutic target in the last two decades. The potential of BAT to oxidize fatty acids rapidly and increase energy expenditure inversely correlates with adiposity, insulin and glucose resistance, and cardiovascular and metabolic diseases. Currently, BAT is recognized by a new molecular signature; several BAT-derived molecules that act positively on target tissues have been identified and collectively called batokines. Bioactive compounds present in foods are endowed with thermogenic properties that increase BAT activation signaling. Understanding the mechanisms that lead to BAT activation and the batokines secreted by it within the thermogenic state is fundamental for its recruitment and management of obesity and NCDs. This review contributes to recent updates on the morphophysiology of BAT, its endocrine role in obesity, and the main bioactive compounds present in foods involved in classical and nonclassical thermogenic pathways activation.

Application of Nanoparticles in Human Nutrition: A Review.

Nanotechnology in human nutrition represents an innovative advance in increasing the bioavailability and efficiency of bioactive compounds. This work delves into the multifaceted dietary contributions of nanoparticles (NPs) and their utilization for improving nutrient absorption and ensuring food safety. NPs exhibit exceptional solubility, a significant surface-to-volume ratio, and diameters ranging from 1 to 100 nm, rendering them invaluable for applications such as tissue engineering and drug delivery, as well as elevating food quality. The encapsulation of vitamins, minerals, and antioxidants within NPs introduces an innovative approach to counteract nutritional instabilities and low solubility, promoting human health. Nanoencapsulation methods have included the production of nanocomposites, nanofibers, and nanoemulsions to benefit the delivery of bioactive food compounds. Nutrition-based nanotechnology and nanoceuticals are examined for their economic viability and potential to increase nutrient absorption. Although the advancement of nanotechnology in food demonstrates promising results, some limitations and concerns related to safety and regulation need to be widely discussed in future research. Thus, the potential of nanotechnology could open new paths for applications and significant advances in food, benefiting human nutrition.

An evaluation of animal models for using bioactive compounds in the treatment of inflammatory bowel disease

AbstractInflammatory bowel disease (IBD) is a prevalent chronic relapsing‐remitting disease that affects the digestive tract and reduces patients’ quality of life. Food bioactive compounds are a promising approach for nutritional intervention of IBD with minimal side effects. To evaluate their potential, researchers have developed various animal models that simulate human IBD, including chemically induced, spontaneous, genetically engineered, and adoptive transfer models. In this work, the main animal models, pathogenesis, symptoms, strengths, and limitations of IBD were discussed. Although these models could not perfectly replicate human IBD, they provided useful tools to study the disease's progression and therapeutic processes. In addition, taking these IBD animals as models, the specific experimental methods, intervention results, and mechanisms of food bioactive compounds to prevent or treat IBD were described in detail. The continuous improvement of animal models is crucial to gain a better understanding of IBD's etiology and pathogenesis and to evaluate the efficacy of food bioactive compounds for the effective control of IBD.

Structured soft particulate matters for delivery of bioactive compounds in foods and functioning in the colon.

The present review discusses challenges, perspectives, and current needs of delivering bioactive compounds (BCs) using soft particulate matters (SPMs) for gut health. SPMs can entrap BCs for incorporation in foods, preserve their bioactivities during processing, storage, and gastrointestinal digestion, and deliver BCs to functioning sites in the colon. To enable these functions, physical, chemical, and biological properties of BCs are integrated in designing various types of SPMs to overcome environmental factors reducing the bioavailability and bioactivity of BCs. The design principles are applied using food grade molecules with the desired properties to produce SPMs by additionally considering the cost, sustainability, and scalability of manufacturing processes. Lastly, to make delivery systems practical, impacts of SPMs on food quality are to be evaluated case by case, and health benefits of functional foods incorporated with delivery systems are to be confirmed and must outweigh the cost of preparing SPMs.

Green Technology for Extraction of Bioactive Compounds from Edible Plants.

In modern society, the use of bioactive compounds in various foods and cosmetic industry sectors through the development of general foods, functional foods, cosmetics, customized cosmetics and several pharmaceuticals has become one of the key technological sources. The most critical step in isolating and purifying bioactive compounds from natural plant materials is the extraction process. Over the past five years, there has been a reasonable compromise between economic, social, and environmental requirements, resulting in safer and more efficient traditional and non-traditional extraction methods. This literature review aims to comprehensively review green extraction technologies for the extraction of bioactive compounds from plant materials from 2020 to 2024.

Orally administered dual-targeted astaxanthin nanoparticles as novel dietary supplements for alleviating hepatocyte oxidative stress.

The enhancement of bioavailability of food bioactive compounds as dietary supplements can be achieved through the development of targeted delivery systems. This study aimed to develop a novel dual-targeted delivery system for hepatocytes and mitochondria using phacoemulsification self-assembly. The delivery systems were engineered by modifying whey protein isolate (WPI) with galactose oligosaccharide (GOS) and triphenylphosphonium (TPP) to improve AXT transport to the liver and promote hepatic well-being. The dual-targeted nanoparticles (AXT@TPP-WPI-GOS) significantly reduced reactive oxygen species in in vitro experiments, thereby slowing down apoptosis. The AXT@TPP-WPI-GOS exhibited a prominent mitochondrial targeting capacity with a Pearson correlation coefficient of 0.76 at 4 h. In vivo pharmacokinetic experiments revealed that AXT@TPP-WPI-GOS could enhance AXT utilization by 28.18 ± 11.69%. Fluorescence imaging in mice demonstrated significantly higher levels of AXT@TPP-WPI-GOS accumulation in the liver compared to that of free AXT. Therefore, these nanoparticles hold promising applications in nutrient fortification, improving the bioavailability of AXT and supporting hepatic well-being.

Masking the bitter taste of quercetin by liposomes modified with whey protein isolate: Better to be coated or inserted?

The unsatisfactory bitterness of quercetin restricts its application to healthy food systems. In this study, whey protein isolate (WPI) inserted and coated quercetin-loaded liposomes were compared in reducing quercetin bitterness and improving the stability of quercetin-loaded liposomes. By electronic tongue and sensory evaluation, the liposomes coated by WPI (0.5–3.0 mg/mL) and inserted with WPI (0.5 mg/mL) significantly reduced the bitterness of quercetin compared to physical mixing. It was also found that the encapsulation efficiency was increased by 15.24% after insertion of WPI at 2.0 mg/mL. The environmental stability results showed that both WPI insertion and coating improved the thermal stability of the quercetin-loaded liposomes compared to the physical mixture, and the WPI coated quercetin-loaded liposomes had the best storage stability and tolerance to salt ions. In contrast, WPI insertion improved the ability of liposomes to resist against surfactant. Raman spectra and fluorescence analysis demonstrated that the modification of WPI reduced the free motion of lipid molecules and promoted the ordering at the polar headgroup area and hydrophobic core of the lipid bilayer. These findings have the potential to support the utilization of WPI modified liposomes as promising option for an efficient transportation of bitter bioactive compounds in nutraceutical and functional foods.

Functional Nutrition as Integrated Intervention for In- and Outpatient with Schizophrenia.

Schizophrenia is a chronic and progressive disorder characterized by cognitive, emotional, and behavioral abnormalities associated with neuronal development and synaptic plasticity alterations. Genetic and epigenetic abnormalities in cortical parvalbumin-positive GABAergic interneurons and consequent alterations in glutamate-mediated excitatory neurotransmission during early neurodevelopment underlie schizophrenia manifestation and progression. Also, epigenetic alterations during pregnancy or early phases of postnatal life are associated with schizophrenia vulnerability and inflammatory processes, which are at the basis of brain pathology and a higher risk of comorbidities, including cardiovascular diseases and metabolic syndrome. In addition, schizophrenia patients adopt an unhealthy lifestyle and poor nutrition, leading to premature death. Here, I explored the role of functional nutrition as an integrated intervention for the long-term management of patients with schizophrenia. Several natural bioactive compounds in plant-based whole foods, including flavonoids, phytonutrients, vitamins, fatty acids, and minerals, modulate brain functioning by targeting neuroinflammation and improving cognitive decline. Although further clinical studies are needed, a functional diet rich in natural bioactive compounds might be effective in synergism with standard treatments to improve schizophrenia symptoms and reduce the risk of comorbidities.

The absorption of bovine milk small extracellular vesicles largely depends on galectin 3 and galactose ligands in human intestinal cells and C57BL/6J mice.

Small extracellular vesicles in milk (sMEVs) have attracted attention in drug delivery and as bioactive food compounds. Previous studies implicate galactose residues on the sMEV surface in sMEV transport across intestinal and endothelial barriers in humans, but details of glycoprotein-dependent transport are unknown. We used a combination of cell biology and genetics protocols to identify glycoproteins on the sMEV surface that facilitate sMEV absorption. We identified 256 proteins on the bovine sMEVs surface by using LC-MS/MS, and bioinformatics analysis suggested that 42, 13, and 13 surface proteins were N-, O-, and 13 C-glycosylated, respectively. Lectin blots confirmed the presence of mannose, galactose, N-acetyl galactose, fucose, and neuraminate. When surface proteins were removed by various treatment with various proteases, sMEV uptake decreased by up to 58% and 67% in FHs-74 Int and Caco-2 cells, respectively, compared with controls (P < 0.05). When glycans were removed by treatment with various glycosidases, sMEV uptake decreased by up to 54% and 74% in FHs-74 Int and Caco-2 cells, respectively (P < 0.05). When galactose and N-acetyl galactosamine residues were blocked with agglutinins, sMEV uptake decreased by more than 50% in FHs-74 Int cells (P < 0.05). When bovine sMEVs were administered to Galectin-3 knockout mice by oral gavage, hepatic sMEV accumulation decreased by 56% compared with wild-type mice (P < 0.05), consistent with a role of β-galactoside glycan structures in the absorption of sMEVs. We conclude that sMEVs are decorated with glycoproteins, and Galectin-3 and its galactose ligands are particularly important for sMEV absorption.NEW & NOTEWORTHY This is the first paper to assess the role of unique glycans and their Galectin-3 receptor in the transport and distribution of small extracellular vesicles ("exosomes") from milk in mammals. The research assessed milk exosome transport and distribution by using multiple approaches and platforms including cell cultures, various exosome labels, knockout and mutant mice, enzymatic removal of surface proteins and glycans, and lectin blocking of glycans.

Effect of pH on the formation mechanisms, emulsifying properties and curcumin encapsulation of oat protein isolate–high methoxy pectin complexes

Oat protein isolate (OPI) has high nutritional value but poor emulsifying properties. The purpose of modifying the OPI with high methoxyl pectin (HMP) was to improve emulsification. In this work, an oat protein isolate (OPI)–high methoxyl pectin (HMP) complex was constructed by changing the pH, and the interactions, formation mechanism and potential use of the OPI–HMP complex as a food emulsifier were explored. The presence of HMP caused structural changes in the OPI, and the changes were pH dependent. When the OPI to HMP mass ratio was 3:1, the critical pH for the phase behavior of OPI–HMP was 5.0. When the pH was greater than 5.0, the OPI and HMP were codissolved in the composite system mainly through electrostatic repulsion. When the pH was 5.0, a soluble OPI–HMP complex was formed by a combination of electrostatic attractions, hydrophobic interactions and hydrogen bonding. At pH values below 5.0, other aggregates of HMP and OPI were generated through electrostatic attraction and hydrogen bonding and formed insoluble aggregates. When the OPI to HMP mass ratio was 3:1 and the pH was 5.0, the particle sizes of the emulsion were the smallest at 8.75 μm due to the strong electrostatic interactions. The emulsification activity and stability were much higher than those of the OPI, and they formed dense osmotic networks, which protected the curcumin. The rates for curcumin encapsulation and retention reached 83.87 ± 1.50% and 88.70 ± 2.50%, respectively, and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate was maintained at a high level (approximately 72%). These results confirmed the possibility of using the OPI-HMP complex emulsions as excellent and stable nutraceutical delivery systems for lipid soluble bioactive compounds in food and biomedical applications.

On surface composition and stability of β-carotene microcapsules comprising pea/whey protein complexes by synchrotron-FTIR microspectroscopy.

This study aims to elucidate the stability of spray dried β-carotene microcapsules by identifying their surface composition using synchrotron-Fourier transform infrared (FTIR) microspectroscopy. To investigate the impact of enzymatic cross-linking and polysaccharide addition on heteroprotein, three wall materials were prepared: pea/whey protein blends (Con), cross-linked pea/whey protein blends (TG), and cross-linked pea/whey protein blends-maltodextrin complex (TG-MD). The TG-MD exhibited the highest encapsulation efficiency (>90%) after 8weeks of storage followed by TG and Con. Chemical images obtained using synchrotron-FTIR microspectroscopy confirmed that the TG-MD displayed the least amount of surface oil, followed by TG and Con, due to increasing amphiphilic β-sheet structure of the proteins led by cross-linking and maltodextrin addition. Both enzymatic cross-linking and polysaccharide addition improved the stability of β-carotene microcapsules, demonstrating that pea/whey protein blends with maltodextrin can be utilised as a hybrid wall material for enhancing the encapsulation efficiency of lipophilic bioactive compounds in foods.

Sorbets as Functional Food Products, Unexplored Food Matrices, Their Challenges, and Advancements

Functional foods and beverages are becoming one of the leading food products on the global market today. This is predominately due to the consumer, industry and research-related interests in the use of food-derived products for the management of several chronic conditions. The diversity of currently available functional food products also provides an opportunity for the use of fruit-based sorbets as a carrier of functional ingredients. Therefore, the aim of this literature review is to explore the use of sorbets as a functional food product, which is one commercial method that can be utilized to provide health benefits, extend the shelf life of foods, and preserve nutrients and improve taste. Firstly, we provide an overview of sorbets as a functional food matrix, their development and implications for the absorption of functional ingredients in humans. We discuss the developmental considerations of functional foods, such as the technical conditions and physicochemical and organoleptic properties through which functional foods can provide beneficial health effects. These include product stability, metabolism of the functional food ingredient, its interactions with the food matrix and limitations related to its production. There is a paucity of clinical data that investigate the long-term health effects of products claiming additional functional benefits. Given the extensive potential benefits of functional bioactive food compounds and their heavy prevalence in the market, extensive research and further regulation is needed to ensure health recommendations for large populations in longitudinal clinical studies warranting any functional claim.

Analysis of Natural Bioactive Compounds in Plant, Food, and Pharmaceutical Products Using Chromatographic Techniques

A growing tendency toward the discovery and use of natural bioactive compounds that are the least harmful, have the fewest side effects, and are the most natural for the human body has been noticed during the past few decades [...]

Green-step assembly of the supramolecular amphiphile constructed by sodium carboxymethyl cellulose and calixarene for facile loading of hydrophobic food bioactive compounds.

The use of biologically active compounds is often limited due to their poor aqueous solubility, which generally reduces their bioavailability and useful efficacy. In this regard, a wide search is currently underway for colloidal systems capable of encapsulating these compounds. In the creation of colloidal systems, long-chain molecules of surfactants and polymers are mainly used, which in an individual state do not always aggregate into homogeneous and stable nanoparticles. In the present work, cavity-bearing calixarene was used for the first time to order polymeric molecules of sodium carboxymethyl cellulose. A set of physicochemical methods demonstrated the spontaneous formation of spherical nanoparticles by non-covalent self-assembly contributed by macrocycle and polymer, and formed nanoparticles were able to encapsulate hydrophobic quercetin and oleic acid. The preparation of nanoparticles by supramolecular self-assembly without use of organic solvents, temperature and ultrasound effects can be an effective strategy for creating water-soluble forms of lipophilic bioactive compounds.

Preparation and structural characterization of pullulan and whey protein isolate-based electrospun nanofiber

The impact of blended ratios was analyzed on the development and characterization of electrospun fibers using various combinations of pullulan (PUL) and whey protein isolate (WPI). The physical parameters like apparent viscosity, electrical conductivity and surface tension of blended solutions were improved after the addition of PUL in the blends, resulting in a uniform electrospun nanofiber. Scanning electron microscope (SEM) of nanofibers revealed bead-free, smooth and uniform structural conformation. Whereas, the uniformity of nanofiber was compromised by using higher concentrations of WPI in the blend. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and Thermogravimetry analysis further confirmed the strong molecular interaction between polysaccharide and protein. The incorporation of WPI in PUL based electrospun nanofibers enhanced hydrophobicity, potentially facilitating the delivery of bioactive compounds. The WPI and PUL:WPI-based nanofibers demonstrated robust antioxidant potential, due to the presence of total phenolic contents (TPC). The stability of PUL interaction with WPI (β-lactoglobulin and α-lactalbumin) was confirmed through hydro-carbon (C–H) and hydrogen bond interactions by molecular docking. Finally, we can conclude that polysaccharide and protein-based nanofiber can be used to deliver bioactive compounds in food and pharmaceutical industries.

Indole-3-carbinol and chlorogenic acid combination modulates gut microbiome and attenuates nonalcoholic steatohepatitis in a murine model

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, affecting almost 32% of the population and ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Recent findings indicate that the fast-growing prevalence of NAFLD might be linked to adherence to a Westernized diet (WD), mostly composed of fat/sugar-enriched foods. The WD has been reportedly targeted as a potential driver of gut-liver axis unbalance, suggesting a major role in NASH. On the other hand, bioactive food compounds feature as a potential chemopreventive strategy against NASH, due to their beneficial effects (i.e, anti-inflammatory/oxidant activity and modulation of gut microbiome). Brassicaceae vegetables are known for their high amount of isothiocyanates and polyphenols, as indole-3-carbinol (I3C) and chlorogenic acid (CGA). Thus, we sought to assess the effects of human relevant doses of I3C and CGA isolated or in combination (5/125 mg/Kg of body weight, respectively) on a diet/chemical-induced murine model of NASH. I3C + CGA oral treatment diminished NAFLD activity score (NAS) (p < 0.0001), as well as alleviated the hepatic lipid (p = 0.0011) accumulation, prevented hepatic stellate cell (HSC) activation (p < 0.0001), and subsequent fibrosis (p < 0.0001). The combination also reduced the number of both hepatic CD68-positive macrophages (p < 0.0001) and cleaved caspase-3 hepatocytes (p < 0.0001) and diminished the malondialdehyde levels (p = 0.0155). Additionally, the combination of I3C + CGA restored the relative abundance of Alistipes (p = 0.0299), Allobaculum (p = 0.0014), Bacteroides (p = 0.0046), and Odoribacter (p = 0.0030) bacteria genera on the gut microbiome. Taken together, these findings show that the combination of I3C + CGA at populational-relevant ingestion, rather than the I3C or CGA alone, was able to modulate gut microbiome and attenuate NASH in this hybrid model mouse.