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Upcycling Vegetable Waste Into Functional Food Ingredients via Synergistic Microbial Engineering and Artificial Intelligence.

The escalating generation of global vegetable waste represents a critical loss of bioactive resources, necessitating a paradigm shift from passive disposal to active nutrient upcycling. However, the industrial conversion of this heterogeneous biomass into standardized functional food ingredients is currently impeded by significant techno-economic barriers, primarily structural recalcitrance, compositional inconsistency, and the presence of toxic fermentation inhibitors. This review provides a comprehensive analysis of the synergistic application of microbial engineering and artificial intelligence (AI) to resolve these bioprocessing bottlenecks within a food-to-food closed-loop framework (as shown in the graphical abstract). We evaluate recent advances in engineering food-grade microbial chassis (e.g., Saccharomyces cerevisiae and Escherichia coli) to enhance lignocellulose degradation and stress tolerance. Concurrently, we examine the integration of AI across the entire value chain, covering deep learning-based rational enzyme design, genome-scale metabolic modeling, and intelligent process control for precision fermentation. Current evidence demonstrates that the hardware-software coupling of engineered strains and AI algorithms significantly enhances conversion efficiency and process robustness. Key findings highlight that AI-driven Design-Build-Test-Learn cycles facilitate the de novo creation of enzymes with superior kinetics and strains with adaptive stress response capabilities against toxins. Moreover, dynamic digital twin models effectively mitigate the impact of substrate variability, ensuring the batch-to-batch consistency required for food applications. We conclude that this data-driven synergistic paradigm is pivotal for establishing a resilient circular bioeconomy, enabling the reliable bioconversion of waste into high-value single-cell proteins, natural flavor additives, and sustainable packaging materials.

Artificial Intelligence↗

Approach to novel functional foods for stress control: 1. Toward structure-activity relationship and data mining of food compounds by chemoinformatics.

Over the past several decades, thousands of natural organic compounds have been isolated from foods, and the information about their structures and biological activities has been accumulated. Despite the long research history of food products and their potential great promise as a medicine and functional food, the systematic research and development have not been carried out extensively. For understanding of the comprehensive structure-activity relationship, we have developed the database system of flavonoids, which are frequently found in vegetables and fruits. We also plan to execute a virtual screening of flavonoids with antidepressant activity by using the database and an advanced chemoinformatic tool. In this section, we will briefly describe (1) flavonoid database and (2) virtual screening of antidepressant compounds.

Antidepressive Agents↗

The importance of GRAS to the functional food and nutraceutical industries.

At a time when 150 million Americans spend over $20.5 billion on functional foods, nutraceuticals and dietary supplements, the Food and Drug Administration (FDA) is doing little to ensure that all the safe and efficacious products that could come to the market are allowed to do so. FDA has only responded slowly and reluctantly to Congressional action and to mandates from the Courts to implement the law. Additionally, FDA had set the bar too high for Health Claims and was forced by the Courts to implement a more reasonable standard, but the response, Qualified Health Claims, has failed to gain the confidence of the public because of the confusing wording of the claims demanded by FDA. Congressional efforts to assure consumer access to dietary supplements have been met with similar resistance from FDA. The Dietary Supplement Health and Education Act (DSHEA) was the product of a compromise with a lower threshold for demonstration of safety (reasonable expectation of no harm) that would be met by consumer self-policing and assumption of some risk. FDA has thwarted this effort by raising the bar for New Dietary Ingredient Notifications (NDIN) to what appears to be the higher threshold for the safety of food ingredients (reasonable certainty of no harm)--FDA apparently sees these two safety thresholds as a distinction without a difference. As a result, increasing numbers of dietary supplement manufacturers, unwilling to gamble the future of their products to a system that provides little hope for the FDA's response of "no objection", have committed the additional resources necessary to obtain Generally Recognized As Safe (GRAS) status for their supplements. The pressure on FDA and Congress for change is again building with increased dissatisfaction among consumers as the result of confusing labels. A second force for change will be a need to uncouple the FDA mandated substance-disease relationship and return to the substance-claim relationship to allow for progress in nutrigenomics and metabolomics, which will result in an increasing number of substance-biomarker claims.

Consumer Product Safety↗

Scientific basis of biomarkers and benefits of functional foods for reduction of disease risk: cancer.

One of the most promising areas for the development of functional foods lies in modification of the activity of the gastrointestinal tract by use of probiotics, prebiotics and synbiotics. While a myriad of healthful effects have been attributed to the probiotic lactic acid bacteria, perhaps the most controversial remains that of anticancer activity. However, it must be emphasised that, to date, there is no direct experimental evidence for cancer suppression in man as a result of consumption of lactic cultures in fermented or unfermented dairy products, although there is a wealth of indirect evidence, based largely on laboratory studies. Presently, there are a large number of biomarkers available for assessing colon cancer risk in dietary intervention studies, which are validated to varying degrees. These include colonic mucosal markers, faecal water markers and immunological markers. Overwhelming evidence from epidemiological, in vivo, in vitro and clinical trial data indicates that a plant-based diet can reduce the risk of chronic disease, particularly cancer. It is now clear that there are components in a plant-based diet other than traditional nutrients that can reduce cancer risk. More than a dozen classes of these biologically active plant chemicals, now known as 'phytochemicals', have been identified. Although the vast number of naturally occurring health-enhancing substances appear to be of plant origin, there are a number of physiologically active components in animal products (such as the probiotics referred to above) that deserve attention for their potential role in cancer prevention.

Biomarkers↗

Metabolically active functional food ingredients for weight control.

The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control.

Adipose Tissue↗

Functional foods and the urinary tract.

There is no universally accepted definition of a commonly used term for a functional food: nutraceutical. For the purposes of this article, a nutraceutical is any ingredient found in foods that has a demonstrated (or proposed) physiologic benefit. Although a nutraceutical is generally taken to be an ingredient that can be isolated or purified from food, plants, or marine products and made available in medicinal form, this article also considers claims of benefit to the urinary tract for foods or food supplements in which the active ingredient has not yet been characterized or isolated.

Animal Feed↗

Are probiotics and other functional foods the medicines of the future?

Many health benefits are being claimed on behalf of so-called 'functional foods', and they are becoming more popular among consumers. But do they really help to prevent and treat disease? This paper discusses their potential uses and looks at current research and opinion, focusing on probiotics, prebiotics and synbiotics, which can be added to foods such as yoghurt.

Animals↗

Functional foods: the Food and Drug Administration perspective.

Because the Federal Food, Drug, and Cosmetic Act (FFDCA) does not provide a statutory definition of functional foods, the Food and Drug Administration has no authority to establish a formal regulatory category for such foods. The primary determinant of the regulatory status of a food is its intended use, which is determined largely by the label and labeling information accompanying the product. This information includes nutrient information, nutrient content claims, and various types of health claims. In marketing these foods, manufacturers may come under one of several existing regulatory options. The first decision manufacturers will make that will help determine their product's regulatory status is whether the product is a food or a drug. Thus, manufacturers and retailers have a range of legal and regulatory categories in which their products may be classified. This article describes the definitions provided in the FFDCA for a drug and a food, the safety and labeling requirements of various food categories, and types of possible claims for dietary supplements.

Dietary Supplements↗

Multi-dimensional profiling of primary metabolites in Heuchera micrantha varieties reveals potential for functional food development.

Heuchera micrantha is a horticultural plant with emerging pharmacological value, yet its primary metabolites remain underexplored. This study comprehensively profiled nutrient metabolites in four H. micrantha varieties using LC-MS/MS. We identified 285 metabolites, with amino acid derivatives being predominant. Multivariate analysis revealed distinct varietal accumulation patterns and 204 differential accumulated metabolites (DAMs). Integrative network pharmacology and molecular docking suggested γ-glutamyltyrosine and L-prolyl-L-phenylalanine as potential bioactive dipeptides that may interact with core hubs (MAPK1, EGFR, SRC) involved in cancer and inflammation pathways, though these predictions require experimental validation. Transcriptomics identified 39 differentially expressed genes regulating the biosynthesis of their precursor amino acids. Antioxidant assays showed varietal differences: some excelled in free radical scavenging (DPPH/ABTS) while others demonstrated superior reducing power (FRAP). This multi-omics study suggests that H. micrantha may be a rich source of therapeutically relevant primary metabolites, providing a preliminary scientific basis for its development as a functional food or nutraceutical pending further validation.

Functional Food↗

The construction of web database server-client system for functional food factors.

In food, other than known nutrients, such as lipid, carbohydrate, protein, vitamins, and minerals, many substances with physiological function and medicinal action exist, and it is contributing to healthy improvement and/or prevention of illness. Although carotenoid, flavonoid and polyphenol, terpenoid, volatile substance and sulfur compounds, peptide, etc. have the function of illness prevention, and research of those non-nutrient functional food factors (FFF) became globally active, the research of this field is not yet done systematically. We evaluate function of FFF and reappraise known knowledge, and this knowledge is standardized and accumulated, aimed at building a web database server-client system which is easy to use for the people and nutritional research. We also collected related data such as chemical characters of FFF from literatures and other source, and formatted them into the database. We constructed the web database server-client system with MySQL database server and Apache web server based on Linux, and used Tomcat JSP engine for data connecting since they were reliable in stability and speed. We are opening the database at http://www.life-science.jp/FFF for test now.

Database Management Systems↗

Identification of a new analogue of sildenafil added illegally to a functional food marketed for penile erectile dysfunction.

A new analogue of sildenafil was discovered to have been added illegally to a functional food marketed for penile erectile dysfunction. The structure of the analogue was established by various NMR spectroscopic techniques (including DEPT, COSY, TOCSY, HMQC, HMBC). Because of the addition of a methylene group to sildenafil, the main ingredient of Viagra(R), it was given the name homosildenafil, and this has never been reported previously. An analytical method using HPLC was proposed. Homosildenafil was added as a new inspection item and other foods have since been discovered to contain it.

Chromatography, High Pressure Liquid↗

Probiotics as functional foods.

Probiotic products have been widely used in Japan and Europe for years. Probiotics are now emerging as an important category of food supplement in the United States. Questions about the biologic nature, available products, claimed health benefits, and safety and regulation of probiotics are important for both consumers and nutrition professionals. Probiotics can be considered functional foods because they provide health benefits beyond the traditional nutrition function. With few exceptions, most probiotic products currently available contain lactic-acid-producing bacteria, which mainly belong to the genera Lactobacillus and Bifidobacterium. We reviewed the scientific papers published in major nutrition journals and abstracts available on the PubMed website regarding probiotics. Evidence suggests the following beneficial effects of probiotics: normalization of the intestinal microflora, ability to block the invasion of potential pathogens in the gut, prophylactic or therapeutic treatment for several types of diarrhea, relief of symptoms of irritable bowel syndrome and inflammatory bowel disease, amelioration of lactose intolerance, prevention of colon cancer, modulation of immune function, inhibition of Helicobacter pylori, and possible enhancement of calcium absorption and reduction of blood cholesterol levels. Mechanisms for the above benefits have been proposed, but none has been proven. An adequate level of viable bacteria in a probiotic product and an appropriate daily dose are critical to achieve a health benefit. Because probiotics are not known to be pathogenic and their upper tolerable level is high, they could be promoted as a beneficial food supplement. Currently, no disease-prevention or therapeutic claim for probiotics is legally allowed.

Journal Article↗

Functional foods for coronary heart disease risk reduction: a meta-analysis using a multivariate approach.

BACKGROUND: It has been difficult to identify the appropriate bioactive substance for the development of new functional foods associated with coronary heart disease, because the results of many clinical studies are contradictory. OBJECTIVE: The objective of this study was to use the multivariate statistical approach known as principal component analysis (PCA) followed by a mixed model to process data obtained from a meta-analysis aimed at evaluating simultaneously the effect of ingestion of 1 of 3 types of bioactive substances (n-3 fatty acids, soluble fibers, and phytosterols) on 1 or more of 4 biomarkers (plasma total cholesterol, triacylglycerol, LDL cholesterol, and HDL cholesterol). DESIGN: Five independent variables (number of patients per study, dose, age, body mass index, and treatment length) and 4 dependent variables (percentage change in blood total cholesterol, LDL, HDL, and triacylglycerol) from 159 studies and substudies were organized into a matrix. The original values were converted to linear correlation units, which resulted in a new matrix. RESULTS: Two principal components were enough to explain 63.73% and 84.27% of the variance in the independent and dependent variables, respectively. Phytosterols and soluble fibers had a hypocholesterolemic effect, whereas n-3 fatty acids lowered triacylglycerol and increased total, LDL, and HDL cholesterol. The PCA and mixed model showed that this behavior was independent of dose, number of patients per study, age, and body mass index but was associated with treatment length. CONCLUSIONS: PCA is useful for summarizing available scientific information in examinations of health claims for foods and supplements.

Cholesterol↗

Exercise and functional foods.

Appropriate nutrition is an essential prerequisite for effective improvement of athletic performance, conditioning, recovery from fatigue after exercise, and avoidance of injury. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widely used in various sporting fields to provide a boost to the recommended daily allowance. In addition, several natural food components have been found to show physiological effects, and some of them are considered to be useful for promoting exercise performance or for prevention of injury. However, these foods should only be used when there is clear scientific evidence and with understanding of the physiological changes caused by exercise. This article describes various "functional foods" that have been reported to be effective for improving exercise performance or health promotion, along with the relevant physiological changes that occur during exercise.

Athletic Injuries↗

Conjugated linoleic acid: a functional food?

Scientific interest in conjugated linoleic acid (CLA) started in 1987 when Michael Pariza's team of Wisconsin University observed its inhibitory effects on chemically induced skin tumors in mice. Numerous studies have since examined CLA's role in cancer, immune function, oxidative stress, atherosclerosis, lipid and fatty acids metabolism, bone formation and composition, obesity, and diabetes. Still it's not clear yet either through which mechanisms CLA produces its numerous metabolic effects. We now know that CLA contents in cow milk fat can be enriched through dry fractionation, but this knowledge doesn't allow sufficient certainty to qualify this nutrient, as a functional food, capable of increasing well being and reducing the risk of disease.

Animals↗

Cytochemical assessment of phosphopeptides derived from casein as potential ingredients for functional food.

Phosphopeptides derived from casein hydrolysis are suggested to have beneficial effects beyond their mere nutritive value by enhancing availability of dietary minerals, especially calcium, iron and zinc. Apart from a possible positive action the potential may exist for adverse effects that could impose restrictions to their widespread application in functional foods for human nutrition. In the present work, various case-inophosphopeptide (CPP) preparations were assessed using different human cell culture model systems in order to estimate their cytotoxic potential and their influence on epithelial properties and differentiation of human intestinal cells (Caco-2). The general cytotoxic potential of CPPs was tested using the AlphaTox NR assay. Structural and functional differentiation of intestinal Caco-2 cells was determined by measuring transepithelial electrical resistance and activity of brush border associated alkaline phosphatase over an extended cultivation period. No loss in cell viability with respect to membrane integrity could be detected, as uptake and retention of neutral red dye (AlphaTox assay) into HeLa cells was not affected by the presence of CPPs. Cytochemical assays conducted on epithelial cells (Caco-2) showed no disturbance of normal cell development and differentiation with respect to structural as well as functional differentiation markers. As all CPPs tested did not provoke any adverse effects in terms of cytotoxicity and showed no impairment of cell differentiation and monolayer integrity of human intestinal cells, it may be supposed that CPPs do not provoke a cytotoxic response in vivo in the cells assayed in the present study.

Alkaline Phosphatase↗

Functional food properties of non-digestible oligosaccharides: a consensus report from the ENDO project (DGXII AIRII-CT94-1095).

This paper results from the final phase of the ENDO project (DGXII AIRII-CT94-1095), a European Commission-funded project on non-digestible oligosaccharides (NDO). All participants in the programme met to perform a consensus exercise on the possible functional food properties of NDO. Topics studied during the project (including a workshop on probiotics and prebiotics) and related aspects, for which considerable evidence has been generated recently, were evaluated on the basis of existing published scientific evidence. There was a general consensus that: (1) there is strong evidence for a prebiotic effect of NDO in human subjects. A prebiotic effect was defined as a food-induced increase in numbers and/or activity predominantly of bifidobacteria and lactic acid bacteria in the human large intestine; (2) there is strong evidence for the impact that NDO have on bowel habit; (3) there is promising evidence that consumption of inulin-type fructans may result in increased Ca absorption in man; (4) there are preliminary indications that inulin-type fructans interact with the functioning of lipid metabolism; (5) there is preliminary evidence in experimental animals of a preventive effect against colon cancer. Human nutrition studies are needed to substantiate these findings. It was concluded that the nutritional properties of NDO may prove to be a key issue in nutritional research in the future.

Animals↗

Olive oil as a functional food: epidemiology and nutritional approaches.

Olive oil is an integral ingredient of the Mediterranean diet and accumulating evidence suggests that it may have health benefits that include reduction of risk factors of coronary heart disease, prevention of several varieties of cancers, and modification of immune and inflammatory responses. Olive oil appears to be an example of a functional food, with varied components that may contribute to its overall therapeutic characteristics. Olive oil is known for its high levels of monounsaturated fatty acids and is also a good source of phytochemicals including polyphenolic compounds, squalene, and alpha-tocopherol.

Cardiovascular Diseases↗