<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN" "JATS-journalpublishing1-4.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.4" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">ym</journal-id>
      <journal-title-group>
        <journal-title>Yangtze Medicine</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2475-7349</issn>
      <issn pub-type="ppub">2475-7330</issn>
      <publisher>
        <publisher-name>Scientific Research Publishing</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.4236/ym.2025.94015</article-id>
      <article-id pub-id-type="publisher-id">ym-147975</article-id>
      <article-categories>
        <subj-group>
          <subject>Article</subject>
        </subj-group>
        <subj-group>
          <subject>Medicine</subject>
          <subject>Healthcare</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Review of Integrating Biotechnology and Functional Foods to Enhance Health and Sustainability</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <contrib-id contrib-id-type="orcid">0009-0009-6349-4531</contrib-id>
          <name name-style="western">
            <surname>Lim</surname>
            <given-names>Enoch Chi Ngai</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-4448-8154</contrib-id>
          <name name-style="western">
            <surname>Lim</surname>
            <given-names>Chi Eung Danforn</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1"><label>1</label> Translational Research Department, Specialist Medical Services Group, Earlwood, Australia </aff>
      <aff id="aff2"><label>2</label> NICM Health Research Institute, Western Sydney University, Westmead, Australia </aff>
      <aff id="aff3"><label>3</label> School of Life Sciences, University of Technology Sydney, Ultimo, Australia </aff>
      <author-notes>
        <fn fn-type="conflict" id="fn-conflict">
          <p>The authors declare no conflicts of interest regarding the publication of this paper.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>15</day>
        <month>12</month>
        <year>2025</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>12</month>
        <year>2025</year>
      </pub-date>
      <volume>09</volume>
      <issue>04</issue>
      <fpage>175</fpage>
      <lpage>187</lpage>
      <history>
        <date date-type="received">
          <day>20</day>
          <month>11</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>12</day>
          <month>12</month>
          <year>2025</year>
        </date>
        <date date-type="published">
          <day>15</day>
          <month>12</month>
          <year>2025</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© 2025 by the authors and Scientific Research Publishing Inc.</copyright-statement>
        <copyright-year>2025</copyright-year>
        <license license-type="open-access">
          <license-p> This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link> ). </license-p>
        </license>
      </permissions>
      <self-uri content-type="doi" xlink:href="https://doi.org/10.4236/ym.2025.94015">https://doi.org/10.4236/ym.2025.94015</self-uri>
      <abstract>
        <p>Technological advances in biotechnology are transforming food production and redefining the link between nutrition, health, and sustainability. From traditional fermentation to genome editing, these tools enable the creation of functional foods that enhance well-being and reduce environmental impact. Historically, low-energy fermentation methods improved the nutritional quality and preservation of foods while supporting gut and metabolic health. Today, emerging fields such as synthetic biology, precision fermentation, microbiome engineering, and artificial intelligence are accelerating innovation in personalised and nutritional approaches that complement conventional diets. These approaches can upcycle agricultural by-products, generate bioactive compounds, and mitigate chronic diseases through targeted microbial or molecular interventions. The purpose of this narrative review is to evaluate the role of biotechnology in developing functional foods that promote health and sustainability. Specifically, it examines how fermentation, biofortification, waste valorisation, and genome editing contribute to metabolic, immune, and cognitive health while supporting environmentally responsible food systems. By integrating traditional food wisdom with modern biosciences, this review highlights biotechnology’s potential to bridge health promotion, sustainability, and innovation in the next generation of functional foods.</p>
      </abstract>
      <kwd-group kwd-group-type="author-generated" xml:lang="en">
        <kwd>Functional Foods</kwd>
        <kwd>Biotechnology</kwd>
        <kwd>Fermentation</kwd>
        <kwd>Microbiome</kwd>
        <kwd>Precision Nutrition</kwd>
        <kwd>Sustainability</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec1">
      <title>1. Introduction</title>
      <p>Functional foods are foods or ingredients that go beyond basic nutrition. They also affect some physiological functions and help mitigate the risk of some chronic diseases. Due to the growing prevalence of non-communicable diseases, such as diabetes and obesity, interest in these foods has increased rapidly. The production of such foods is also challenged by global population growth, climate change, and the impending food supply crisis. Hence, there is a need for health-affirming and health-sustaining foods. Biotechnology could help address these challenges. It is the increasing manipulation of living organisms developed for specific purposes. These organisms may improve the nutrient value of crops, convert agricultural waste into value-added ingredients, or engineered microbes and enzymes may perform specific health-promoting functions. Although many of these techniques are not new, as they build on established practices such as fermentation, they are novel in that they provide tremendous precision at the molecular level.</p>
      <sec id="sec1dot1">
        <title>Methodology</title>
        <p>This review was developed through an extensive literature search focused on peer-reviewed articles published between 2015 and 2025. Databases searched included PubMed, Scopus and Web of Science. Keywords such as “functional foods,” “biotechnology,” “fermentation,” “microbiome,” and “precision nutrition” were combined with terms related to sustainability and chronic disease. Preference was given to papers published within the last five years to ensure currency of evidence. Classic reviews were included when they provided historical context. From the initial search results, titles and abstracts were screened for relevance. Full-text articles were assessed and grouped by thematic categories aligned with the structure of this article. Studies on culinary medicine and traditional Chinese dietary therapy were included to capture the intersection between food culture and modern science. Regulatory documents from the U.S. Food and Drug Administration (FDA) were examined to describe clinical and policy developments.</p>
      </sec>
    </sec>
    <sec id="sec2">
      <title>2. Lessons from Culinary Medicine &amp; Fermented Foods</title>
      <sec id="sec2dot1">
        <title>2.1. Culinary Medicine and Chinese Dietary Therapy</title>
        <p>Culinary medicine (CM) blends nutrition science with practical cooking to help individuals choose foods that support their health. Unlike general dietetics or nutritional counselling, CM emphasises hands-on skills and patient-specific advice. A U.S. government article describes culinary medicine as an evidence-based field that utilises food to prevent and treat disease [<xref ref-type="bibr" rid="B1">1</xref>]. In programs for ethnically diverse patients with type 2 diabetes, CM interventions increase the consumption of healthy foods and provide a supportive community environment [<xref ref-type="bibr" rid="B2">2</xref>][<xref ref-type="bibr" rid="B3">3</xref>]. CM also draws on cultural food traditions. Traditional Chinese medicine (TCM) incorporates medicinal foods and dietary regulation to maintain balance in the body. A recent review summarises clinical trials in which TCM dietary therapy may improve blood glucose, triglyceride levels, and body mass index in patients with impaired glucose tolerance or prediabetes [<xref ref-type="bibr" rid="B3">3</xref>]. The interventions used medicated diets tailored to the patient’s constitution, demonstrating the potential of personalised nutrition within traditional frameworks.</p>
        <p>The mechanisms proposed for TCM diet therapy include insulin-like bioactive compounds, high dietary fibre that slows glucose absorption, inhibition of adipocyte proliferation, and anti-inflammatory effects [<xref ref-type="bibr" rid="B4">4</xref>]. For example, recipes such as Jianpi Qushi replace certain staple foods with herb-enriched dishes and have shown superior improvements in fasting plasma glucose and two-hour postprandial glucose compared with routine health education [<xref ref-type="bibr" rid="B4">4</xref>]. These findings demonstrate the benefits of food in its own right. They also highlight the importance of local food knowledge and cultural context, which biotechnology can complement but should not supplant. Modern biotechnology can augment TCM dietary therapy by producing defined bioactive compounds found in medicinal foods. For example, precision fermentation can be used to synthesise key metabolites such as berberine-like alkaloids or ginsenoside analogues, enabling standardised functional ingredients that mirror therapeutic components of traditional herbs.</p>
      </sec>
      <sec id="sec2dot2">
        <title>2.2. Fermented Foods: Ancient Biotechnology</title>
        <p>Fermentation is one of humanity’s oldest biotechnologies. Microorganisms metabolise sugars and other substrates to produce acids, alcohols and gases, thereby preserving food and altering its flavour and texture [<xref ref-type="bibr" rid="B5">5</xref>]. A 2022 review notes that fermented foods have been part of the human diet for nearly 10,000 years and contain bioactive peptides and metabolites that confer health benefits [<xref ref-type="bibr" rid="B6">6</xref>]. These foods include dairy products, sauerkraut, kimchi, sourdough breads and fermented beverages. The lactic acid fermentation process, employed with bacteria and yeasts, yields longer-lasting products, enhances digestibility, and generates valuable end products, including certain vitamins, short-chain fatty acids (SCFAs), and bioactive antioxidant peptides [<xref ref-type="bibr" rid="B5">5</xref>][<xref ref-type="bibr" rid="B6">6</xref>].</p>
        <p>There are also sustainable and environmental benefits associated with fermentation. The process requires minimal energy, can be carried out on-site, and eliminates the need for refrigerated storage in the short term. Thus, it lessens waste and fortifies the resilience of food systems. In addition to all of these, fermented products also modify gut microbiomes, since the live microorganisms contained in the food products can withstand the rigours of the digestive tract, and interact with gut communities, thus modulating immune and metabolic functions [<xref ref-type="bibr" rid="B5">5</xref>][<xref ref-type="bibr" rid="B6">6</xref>]. The natural preservation of food and the therapeutic benefits of fermented products have increased interest in them.</p>
      </sec>
      <sec id="sec2dot3">
        <title>2.3. Sustainability and Therapeutic Overlap</title>
        <p>As with several other fields in the health and wellness sector, culinary medicine, diet therapy within traditional Chinese medicine, and the practice of incorporating fermented foods into one’s diet are interconnected through the common theme of bioactive compounds. Numerous culinary medicine recipes incorporate fermented foods, for example, miso, yoghurt, and tempeh. In TCM, diet therapy also frequently incorporates fermented soy products, such as natto, which is a source of vitamin K and bioactive peptides of considerable health importance. These foods are also a source of prebiotics and probiotics, and consequently strengthen the gut system [<xref ref-type="bibr" rid="B5">5</xref>]. The preparation processes for these foods are relatively low-energy and utilise local ingredients, which also aligns with the principles of sustainability. Biotechnology, in terms of strain selection or engineering for higher targeted metabolite production, will only enhance several of these practices. Biotechnology will help to standardise production systems for defined health outcomes.</p>
      </sec>
    </sec>
    <sec id="sec3">
      <title>3. Modern Biotechnology Tools for Functional Foods</title>
      <sec id="sec3dot1">
        <title>3.1. Microbiome‑Targeted Therapies and Engineered Probiotics</title>
        <p>The ability to modify the microbiome in the treatment of disorders is a novel application in the field of microbiome research [<xref ref-type="bibr" rid="B7">7</xref>]. The use of probiotics, prebiotics, and faecal microbiota transplantation (FMT) is one of the most common techniques. Targeting the microbiome through the use of probiotics, prebiotics, bacteriophages, and engineered bacteria has been reviewed. The review [<xref ref-type="bibr" rid="B7">7</xref>] mentions high cure rates for recurrent Clostridioides difficile infections (CDI) and a modest treatment success rate for inflammatory bowel disease. These treatments are designed to restore microbial diversity, modulate immune responses, increase levels of SCFAs, and enhance immune and anti-inflammatory SCFA production.</p>
        <p>Synthetic probiotics modify bacterial functions in novel ways, using tools of synthetic biology. The creation of live biotherapeutic bacteria and biosensors that detect inflammatory molecules and control the release of therapeutic agents [<xref ref-type="bibr" rid="B8">8</xref>] takes biosensing to the next level. These control systems target the recognised limitations of some conventional probiotics, whose colonisation is often transient and whose actions may be non-specific depending on the strain [<xref ref-type="bibr" rid="B8">8</xref>]. Constructing a strain with a genetic circuit to release anti-inflammatory peptides or degrade toxic metabolites demonstrates the potential of modern biotechnology tools to augment the benefits of probiotics.</p>
      </sec>
      <sec id="sec3dot2">
        <title>3.2. Postbiotics and Metabolite-Based Foods</title>
        <p>Postbiotics, which are non-viable bacterial components and metabolites, are emerging as functional food ingredients. They include soluble factors, cell wall fragments, and secreted molecules that provide health effects without the risks linked to live microbes [<xref ref-type="bibr" rid="B9">9</xref>]. Postbiotics are naturally found in fermented foods such as yoghurt, sauerkraut, and kombucha [<xref ref-type="bibr" rid="B9">9</xref>]. Their stability allows use in foods that are unsuitable for live probiotics. Research has shown antibacterial, antiviral, and anti-diabetic effects from different postbiotic preparations [<xref ref-type="bibr" rid="B9">9</xref>]. From a commercial perspective, postbiotic ingredients offer a way to supply bioactive compounds on a large scale without the need for live fermentation at the point of consumption.</p>
      </sec>
      <sec id="sec3dot3">
        <title>3.3. Precision Fermentation and Bioreactors</title>
        <p>Precision fermentation utilises microorganisms in controlled bioreactors to produce specific compounds that are traditionally obtained from animals or plants. The Food and Agriculture Organization of the United Nations (FAO) report describes how bacteria, yeasts, fungi, and microalgae can be programmed to synthesise proteins, fats, vitamins, and pigments [<xref ref-type="bibr" rid="B10">10</xref>]. The process involves upstream fermentation, where microbes are cultured to produce the target molecule, and downstream processing to purify it. Precision fermentation can create alternatives to dairy proteins, eggs and fish oils with a smaller environmental footprint. It also allows the production of bioactive peptides and metabolites for functional foods. These products are free from allergens, pathogens or contaminants that may be present in animal-derived ingredients. The scalability of bioreactors enables consistent production and reduces reliance on agricultural land.</p>
      </sec>
      <sec id="sec3dot4">
        <title>3.4. Genome Editing and Biofortification</title>
        <p>Gene editing tools, such as CRISPR-Cas9, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs), enable targeted modifications to the genomes of plants and microorganisms. CRISPR systems are particularly efficient and cost-effective, with RNA guides directing Cas endonucleases to specific DNA sequences [<xref ref-type="bibr" rid="B11">11</xref>]. Base editing and prime editing further reduce off-target effects. In plants, genome editing has been used to knock out genes that limit the accumulation of micronutrients. For example, CRISPR-Cas9 targeting of the rice gene OsZIP9 decreased zinc flux, revealing its role as a transporter [<xref ref-type="bibr" rid="B11">11</xref>]. Editing of OsNramp5 reduced cadmium accumulation and improved iron transport [<xref ref-type="bibr" rid="B11">11</xref>]. By modifying regulatory elements of genes involved in iron and zinc homeostasis, researchers can increase micronutrient content in crops [<xref ref-type="bibr" rid="B11">11</xref>].</p>
        <p>Microbial fermentation also serves as a biofortification strategy. Fermentation can synthesise vitamins and increase mineral bioavailability in plant-based foods. Studies demonstrate that certain bacteria and yeasts raise levels of vitamin B<sub>2</sub>, B<sub>6</sub> and B<sub>12</sub> during fermentation [<xref ref-type="bibr" rid="B12">12</xref>]. For instance, fermentation of brewers’ spent grain with <italic>Propionibacterium</italic><italic>freudenreichii</italic> enriched the material with vitamin B<sub>12</sub>, yielding 21 micrograms per 100 g after optimisation [<xref ref-type="bibr" rid="B12">12</xref>]. Co-fermentation of soymilk with riboflavin-producing <italic>Lactiplantibacillus</italic><italic>plantarum</italic> and Lactobacillus acidophilus tripled riboflavin levels and improved sensory qualities [<xref ref-type="bibr" rid="B12">12</xref>]. Fermentation of orange juice with <italic>Lactiplantibacillus</italic><italic>plantarum</italic> increased vitamin C content by about 19 per cent compared with unfermented juice [<xref ref-type="bibr" rid="B12">12</xref>]. These examples demonstrate that biotechnology can enhance the nutrient profile of foods without necessitating the genetic modification of crops. The wide array of biotechnology tools, their functional ingredients, health targets, and regulatory status are summarised in <bold>Table 1</bold>. The prefix “non” is not a word; it should be joined to the word it modifies, usually without a hyphen.</p>
        <p><bold>Table 1</bold><bold>.</bold>Biotechnology modalities, target ingredients, health outcomes and regulatory maturity.</p>
        <table-wrap id="tbl1">
          <label>Table 1</label>
          <table>
            <tbody>
              <tr>
                <td>Modality/Tool</td>
                <td>Platform/Strain or Crop</td>
                <td>Target ingredient/biomolecule</td>
                <td>Primary health target</td>
                <td>Example product/claim</td>
                <td>Maturity/regulatory snapshot</td>
              </tr>
              <tr>
                <td>Precision fermentation</td>
                <td>Microalgae/yeast cell factories</td>
                <td>EPA/DHA</td>
                <td>Cardiometabolic &amp; cognitive support</td>
                <td>Microbial omega-3 oils</td>
                <td>Commercialising; “novel food/ingredient”</td>
              </tr>
              <tr>
                <td>Engineered probiotics</td>
                <td>Synthetic circuits in probiotic chassis</td>
                <td>Anti-inflammatory peptides</td>
                <td>IBD, gut inflammation</td>
                <td>Live biotherapeutic concept foods</td>
                <td>Preclinical/early clinical trials</td>
              </tr>
              <tr>
                <td>Postbiotics</td>
                <td>Fermented foods (e.g., yoghurt, sauerkraut)</td>
                <td>SCFAs, cell wall fragments</td>
                <td>Immune and metabolic modulation</td>
                <td>Stabilised powders</td>
                <td>Food ingredient; stable in processing</td>
              </tr>
              <tr>
                <td>Genome editing/biofort.</td>
                <td>Edited rice (e.g., OsZIP9, OsNramp5)</td>
                <td>↑Fe/↑Zn, ↓Cd</td>
                <td>Micronutrient adequacy</td>
                <td>Biofortified staples</td>
                <td>R&amp;D/field; jurisdiction-specific approval</td>
              </tr>
              <tr>
                <td>Microbiome therapeutics</td>
                <td>
                  Rebyota
                  <sup>®</sup>
                  , Vowst
                  <sup>®</sup>
                </td>
                <td>Diverse microbes/spores</td>
                <td>Prevent recurrent CDI</td>
                <td>FDA-approved therapies</td>
                <td>Drug/biologic classification</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Footnotes: EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; IBD: Inflammatory bowel disease; SCFAs: Short-chain fatty acids; OsZIP9, OsNramp5: rice transporter genes linked to Zn and Cd flux; Fe: iron; Zn: zinc; Cd: cadmium; R&amp;D: research and development; CDI: Clostridioides difficile infection; FDA: U.S. Food and Drug Administration.</p>
      </sec>
      <sec id="sec3dot5">
        <title>3.5. Bioreactors as Sustainable Alternatives to Animal‑Sourced Nutrients</title>
        <p>Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential for human health and are traditionally obtained from fish oil. Overfishing and environmental contamination limit supply. A 2023 review notes that synthetic biology and engineered microbial cell factories can produce stable and affordable sources of EPA and DHA [<xref ref-type="bibr" rid="B13">13</xref>]. Microalgae and yeast strains have been engineered to synthesise long-chain polyunsaturated fatty acids. Production in bioreactors reduces demand on marine ecosystems and provides a sustainable ingredient for functional foods. Combined with fermentation technologies, these approaches demonstrate how biotechnology can provide nutrients while minimising ecological impact.</p>
      </sec>
    </sec>
    <sec id="sec4">
      <title>4. Biotechnology for Sustainability</title>
      <sec id="sec4dot1">
        <title>4.1. Waste‑to‑Value Conversion</title>
        <p>The food industry generates significant waste. Up to 60 percent of vegetable processing output comprises peels, stems and other by-products that are rich in bioactive compounds [<xref ref-type="bibr" rid="B14">14</xref>]. These materials often end up in landfills, resulting in both environmental and economic losses. Fermentation offers a sustainable approach for converting agro-industrial waste into valuable functional ingredients. A 2025 review reports that the fermentation of vegetable by-products improves digestibility, reduces anti-nutritional factors, and adds probiotic cultures [<xref ref-type="bibr" rid="B14">14</xref>]. For example, lactic acid fermentation of carrot pomace produces a fibre-rich ingredient with enhanced mineral bioavailability. Fermentation of soybean meal with Bacillus licheniformis reduces phytic acid and increases protein hydrolysis [<xref ref-type="bibr" rid="B12">12</xref>]. These processes transform waste into value-added products, contributing to a circular economy.</p>
      </sec>
      <sec id="sec4dot2">
        <title>4.2. Biotechnological Biofortification</title>
        <p>Biofortification aims to increase the density and bioavailability of micronutrients in foods. Beyond genome editing, microbial fermentation can biosynthesise vitamins and minerals in plant-based matrices. Fermentation of oat and rice beverages with specific lactic acid bacteria strains increases the riboflavin content and produces prebiotic dextrans [<xref ref-type="bibr" rid="B12">12</xref>]. Fermented orange juice shows elevated vitamin C and shikimic acid due to microbial biosynthesis [<xref ref-type="bibr" rid="B12">12</xref>]. Fermentation of seeds and beans with <italic>Bacillus subtilis</italic> var. natto enhances vitamin K<sub>2</sub> (menaquinone 7) levels, with sunflower seeds reaching over 1000 micrograms per 100 g [<xref ref-type="bibr" rid="B12">12</xref>]. Microbial processes can also convert precursors into more bioactive forms; for example, fermentation converts provitamin A carotenoids into retinol equivalents [<xref ref-type="bibr" rid="B12">12</xref>]. These examples demonstrate scalable routes to fortify plant foods without synthetic additives. Specific examples of nutrient enrichment mediated by fermentation are outlined in <bold>Table 2</bold>.</p>
        <p><bold>Table 2</bold><bold>.</bold> Examples of fermentation processes enhancing micronutrient content.</p>
        <table-wrap id="tbl2">
          <label>Table 2</label>
          <table>
            <tbody>
              <tr>
                <td>Substrate/food matrix</td>
                <td>Microbe/strain &amp; process</td>
                <td>Nutrient/metabolite</td>
                <td>Baseline</td>
                <td>Post-fermentation</td>
                <td>% change</td>
                <td>Sensory/quality notes</td>
              </tr>
              <tr>
                <td>Brewers’ spent grain</td>
                <td>
                  <italic>Propionibacterium</italic>
                  <italic>freudenreichii</italic>
                  (optimised)
                </td>
                <td>Vitamin B12</td>
                <td>~0 µg/100 g</td>
                <td>21 µg/100 g</td>
                <td>—</td>
                <td>Improved yield post-optim.</td>
              </tr>
              <tr>
                <td>Soymilk</td>
                <td>
                  <italic>L. plantarum</italic>
                  +
                  <italic>L. acidophilu</italic>
                  s (co-ferm.)
                </td>
                <td>Riboflavin (B2)</td>
                <td>1×</td>
                <td>3×</td>
                <td>+200%</td>
                <td>Improved flavour profile</td>
              </tr>
              <tr>
                <td>Orange juice</td>
                <td>
                  <italic>L. plantarum</italic>
                </td>
                <td>Vitamin C</td>
                <td>100% baseline</td>
                <td>119%</td>
                <td>+19%</td>
                <td>Comparable taste</td>
              </tr>
              <tr>
                <td>Sunflower seeds (natto)</td>
                <td>
                  <italic>B. subtilis</italic>
                  var. natto
                </td>
                <td>Vitamin K2 (MK-7)</td>
                <td>Low</td>
                <td>&gt;1000 µg/100 g</td>
                <td>—</td>
                <td>—</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Footnotes: µg: microgram; g: gram; L.: Lactobacillus/Lactiplantibacillus genus; co-ferm.: co-fermentation; B2: riboflavin; MK-7: menaquinone-7 (a form of vitamin K2).</p>
      </sec>
      <sec id="sec4dot3">
        <title>4.3. Food Safety and Standardisation</title>
        <p>Fermentation and microbial engineering provide sustainability benefits, yet they also raise safety concerns. Donor-derived live biotherapeutic products (LBPs), such as Rebyota and Vowst, require strict screening to prevent the transmission of pathogens or allergens. Rebyota is made from screened human stool, processed into a 150-millilitre enema that contains a diverse mix of microbes, and administered as a single rectal dose [<xref ref-type="bibr" rid="B7">7</xref>][<xref ref-type="bibr" rid="B15">15</xref>]. Vowst, approved in 2023, utilises ethanol-treated spore preparations administered orally following bowel washout [<xref ref-type="bibr" rid="B7">7</xref>][<xref ref-type="bibr" rid="B15">15</xref>]. Manufacturing encompasses pathogen testing, cryopreservation, and controlled thawing to ensure product quality is maintained. Industrial-scale fermented foods must follow Hazard Analysis and Critical Control Point (HACCP) systems. Biotechnology can enhance safety by engineering strains that lack antibiotic resistance genes or virulence factors, and by utilising genomic sequencing to monitor microbial communities during production. Standards bodies, including EFSA and FSANZ, are building frameworks to assess both health claims and the safety of functional foods.</p>
      </sec>
      <sec id="sec4dot4">
        <title>4.4. Environmental Footprint</title>
        <p>Biotechnology can reduce the environmental footprint of food production. Precision fermentation requires less land and water than animal agriculture and produces lower greenhouse gas emissions. Bioreactors operate in controlled environments and can be powered by renewable energy. Using agricultural by-products as substrates further decreases waste and avoids competition with food crops. CRISPR-enabled biofortification may reduce the need for synthetic fertilisers and reduce soil depletion. Microbial production of omega-3 fatty acids reduces pressure on marine ecosystems [<xref ref-type="bibr" rid="B13">13</xref>]. Collectively, these technologies support climate-smart agriculture by enhancing resource efficiency and reducing greenhouse gas emissions.</p>
      </sec>
    </sec>
    <sec id="sec5">
      <title>5. Health Enhancement Pathways</title>
      <p><bold>Table 3</bold> summarises selected microbiome and biotechnology-based products, their regulatory classifications, and implications for functional food positioning.</p>
      <p><bold>Table 3</bold><bold>.</bold> Regulatory and clinical landscape of biotechnology-derived products.</p>
      <table-wrap id="tbl3">
        <label>Table 3</label>
        <table>
          <tbody>
            <tr>
              <td>Product/ingredient</td>
              <td>Classification (AU/EU/US)</td>
              <td>Intended use/indication</td>
              <td>Formulation &amp; route</td>
              <td>Core evidence</td>
              <td>Quality/safety controls</td>
              <td>Notes for functional food positioning</td>
            </tr>
            <tr>
              <td>
                Rebyota
                <sup>®</sup>
              </td>
              <td>Biologic (drug)</td>
              <td>Prevent recurrent CDI</td>
              <td>150 mL rectal enema, single dose</td>
              <td>FDA approval 2022</td>
              <td>Donor screening, pathogen testing</td>
              <td>Not a food; sets regulatory benchmark</td>
            </tr>
            <tr>
              <td>
                Vowst
                <sup>®</sup>
              </td>
              <td>Biologic (drug)</td>
              <td>Prevent recurrent CDI</td>
              <td>Oral spore capsules</td>
              <td>RCT: recurrence ↓ 39.8→12.4%</td>
              <td>GMP, ethanol treatment</td>
              <td>Therapeutic; contrast for food claims</td>
            </tr>
            <tr>
              <td>Postbiotic powder (generic)</td>
              <td>Food/novel food ingredient</td>
              <td>Immune/metabolic support</td>
              <td>Heat-killed fractions/ metabolites</td>
              <td>Growing evidence</td>
              <td>Identity/purity specs</td>
              <td>Stable; label as postbiotic</td>
            </tr>
            <tr>
              <td>Precision-fermented omega-3</td>
              <td>Food/novel ingredient</td>
              <td>Heart and brain health</td>
              <td>Oil from yeast/microalgae</td>
              <td>Reviews on sustainability</td>
              <td>Residual solvent, allergen checks</td>
              <td>Marine-free EPA/DHA alternative</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>Footnotes: AU: Australia; EU: European Union; US: United States; CDI: Clostridioides difficile infection; FDA: U.S. Food and Drug Administration; RCT: randomised controlled trial; GMP: good manufacturing practice; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid.</p>
      <sec id="sec5dot1">
        <title>5.1. Metabolic Health: Diabetes, Obesity and Non‑Alcoholic Fatty Liver Disease</title>
        <p>Functional foods derived from fermentation and biotechnology can improve metabolic health. TCM dietary therapy has demonstrated improvements in fasting plasma glucose, two-hour postprandial glucose, and glycated haemoglobin in patients with impaired glucose tolerance or type 2 diabetes [<xref ref-type="bibr" rid="B4">4</xref>]. Mechanistic explanations include insulin-like compounds, high fibre content, and anti-inflammatory effects [<xref ref-type="bibr" rid="B4">4</xref>]. Fermented foods supply SCFAs such as acetate, propionate and butyrate that modulate energy metabolism and insulin sensitivity. Microbiome-targeted therapies aim to restore microbial balance and increase SCFA production. Probiotics engineered to secrete GLP-1 analogues or amylin mimetics could support glycaemic control. Faecal microbiota products, such as Rebyota and Vowst, are being explored for metabolic conditions beyond CDI. Engineered probiotics and postbiotic supplements may deliver specific metabolites, such as ursolic acid or conjugated linoleic acid, that influence lipid metabolism.</p>
      </sec>
      <sec id="sec5dot2">
        <title>5.2. Immune Modulation and Gut Barrier Function</title>
        <p>Fermented foods and probiotics strengthen gut barrier integrity and modulate immune responses. The beneficial microbes in fermented foods interact with pattern recognition receptors on intestinal epithelial cells, promoting the production of anti-inflammatory cytokines and enhancing secretory immunoglobulin A. Engineered probiotics can be designed to sense inflammation and secrete anti-inflammatory compounds [<xref ref-type="bibr" rid="B8">8</xref>]. Bacteriophage therapy, a component of microbiome-targeted approaches, can selectively eliminate pathogens and reduce dysbiosis. Postbiotics, which contain cell wall fragments or microbial metabolites, also exert immunomodulatory effects [<xref ref-type="bibr" rid="B9">9</xref>]. These interventions could complement treatment for immune-mediated conditions such as inflammatory bowel disease and allergies.</p>
      </sec>
      <sec id="sec5dot3">
        <title>5.3. Gut-Brain Axis and Mental Health</title>
        <p>The gut-brain axis links gastrointestinal function with mood and cognition [<xref ref-type="bibr" rid="B5">5</xref>]. Fermented foods produce neurotransmitter precursors and neuromodulatory metabolites, such as gamma-aminobutyric acid, serotonin, and tryptophan derivatives. Consumption of fermented dairy and vegetables has been associated with lower levels of anxiety and depressive symptoms [<xref ref-type="bibr" rid="B5">5</xref>]. Microbiome-targeted therapies may influence brain function via vagal signalling and immune modulation [<xref ref-type="bibr" rid="B5">5</xref>]. Engineered probiotics that synthesise neuroactive compounds or degrade toxins are under investigation. Combining fermented food traditions with synthetic biology could lead to foods that support mental well-being. The integration of AI-guided microbiome profiling with CM may identify dietary patterns that enhance mood and cognitive performance.</p>
      </sec>
      <sec id="sec5dot4">
        <title>5.4. Personalised Nutrition</title>
        <p>Artificial intelligence is increasingly used to tailor diets based on individual data. A systematic review of AI-generated dietary recommendations notes that these systems map interactions among biomarkers, gut microbiome profiles, and dietary components to produce personalised plans [<xref ref-type="bibr" rid="B16">16</xref>]. Preliminary studies report improved glycaemic control and symptom relief in conditions such as irritable bowel syndrome and prediabetes. Wearable sensors and continuous glucose monitors provide real-time data that enable the rapid adjustment of dietary advice [<xref ref-type="bibr" rid="B16">16</xref>]. However, ethical and practical challenges remain, including data privacy, algorithm transparency, and user adherence [<xref ref-type="bibr" rid="B16">16</xref>]. AI could integrate TCM constitutional typing [<xref ref-type="bibr" rid="B17">17</xref>] with microbiome profiling to personalise functional foods. For example, individuals with a phlegm-damp constitution might benefit from fermented, fibre-rich foods and specific probiotics, whereas those with yin deficiency might benefit from cooling ingredients and anti-inflammatory compounds. Recent conceptual frameworks have proposed combining AI-driven pattern recognition with traditional constitutional diagnostics to generate hybrid models for personalised nutrition [<xref ref-type="bibr" rid="B17">17</xref>].</p>
      </sec>
      <sec id="sec5dot5">
        <title>5.5. Public Perception and Consumer Acceptance</title>
        <p>Despite strong scientific progress, public perception of biotechnologies such as genome editing, precision fermentation and engineered microbes remains mixed. Surveys in Australia, Europe and the United States indicate higher acceptance when products provide clear health or sustainability benefits, but hesitancy persists around concepts perceived as artificial or genetically modified. Transparent communication, culturally appropriate framing, and clear labelling are therefore essential for consumer trust and market adoption. Acceptance will depend not only on scientific merit but also on perceived naturalness, safety and ethical considerations.</p>
      </sec>
    </sec>
    <sec id="sec6">
      <title>6. Clinical and Regulatory Outlook</title>
      <p>Regulatory agencies are beginning to approve microbiome-based therapeutics. In November 2022, the FDA approved Rebyota, the first live biotherapeutic product for preventing recurrence of CDI. It consists of screened donor stool processed into a 150-millilitre enema containing a diverse mix of microbes and is administered as a single rectal dose [<xref ref-type="bibr" rid="B15">15</xref>]. In April 2023, the FDA approved Vowst, the first orally administered FMT product made of ethanol-treated spores, to prevent recurrent CDI [<xref ref-type="bibr" rid="B18">18</xref>]. In a placebo-controlled trial, Vowst reduced recurrence from 39.8 percent to 12.4 per cent [<xref ref-type="bibr" rid="B19">19</xref>]. These approvals set precedents for other microbiome therapies and underscore the importance of rigorous donor screening and manufacturing controls. European and Australian regulatory bodies are also developing frameworks for functional foods and microbiome-based therapeutics.</p>
      <p>Engineered probiotics and postbiotic ingredients remain in experimental stages. Regulatory questions include how to classify these products—as drugs, supplements or foods—and what safety testing is required. Randomised controlled trials with omics-based endpoints are needed to establish efficacy and long-term safety. Standardisation of microbial strains and fermentation conditions will be critical for reproducibility. Policymakers must also address equitable access, reimbursement and labelling. As more AI-guided nutrition platforms emerge, regulators will need to consider data privacy and algorithmic fairness.</p>
    </sec>
    <sec id="sec7">
      <title>7. Clinical and Regulatory Outlook</title>
      <p>The convergence of ancient food wisdom and modern biotechnology offers exciting opportunities. Fermentation, once a household practice, now benefits from genomic tools that optimise microbial consortia for nutrient production, flavour and safety. Precision fermentation can generate animal-free proteins and fats. Genome editing enables crops to store key micronutrients. Artificial intelligence can combine microbiome profiles, metabolic markers, and traditional diagnostic approaches to design personalised diets.</p>
      <p>Policy and market growth will play a central role. Governments should fund research on sustainable fermentation, promote the use of agricultural by-products as substrates, and set clear regulatory pathways for functional foods and microbiome therapies. Partnerships between researchers, industry, and local communities can help adapt new technologies into culturally appropriate foods. Sustainable functional foods can support healthier diets, cut environmental impact, and preserve culinary traditions. Biotechnology functions as a bridge linking food production, sustainability, and health.</p>
    </sec>
    <sec id="sec8">
      <title>8. Conclusion</title>
      <p>The intersection of traditional knowledge and modern science is evident in the functional foods made possible by biotechnology. Advanced techniques, such as precision fermentation, synthetic biology, and biofortification, enable the production of foods that are not only nutrient-dense but also promote metabolic, immune, and cognitive health, as well as overall wellness. Upcycling and additional efficient production methods are ways to reduce waste and mitigate the environmental impact of food production. Engineered probiotics and postbiotics can offer specific benefits that bypass the need for live microbial colonisation. Defined expectations among regulators, industry partners, researchers and consumers, combined with unimpeded dialogue across scientific, policy and community sectors, will support responsible innovation. Ensuring equitable distribution of biotechnological advances, particularly access to functional foods and sustainable nutrition solutions, will be essential to translating progress into tangible public health benefits. The incorporation of microbiome science into food formulation could lead to hyper-personalised dietary regimens. Sustained cooperation among researchers, industry and policymakers will be crucial for biotechnological progress to benefit human health and protect the environment.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">La Puma, J. (2016) What Is Culinary Medicine and What Does It Do? <italic>Population Health Management</italic>, 19, 1-3. https://doi.org/10.1089/pop.2015.0003 <pub-id pub-id-type="doi">10.1089/pop.2015.0003</pub-id><pub-id pub-id-type="pmid">26035069</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1089/pop.2015.0003">https://doi.org/10.1089/pop.2015.0003</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Puma, J.</string-name>
            </person-group>
            <year>2016</year>
            <article-title>What Is Culinary Medicine and What Does It Do? Population Health Management, 19, 1-3</article-title>
            <pub-id pub-id-type="doi">10.1089/pop.2015.0003</pub-id>
            <pub-id pub-id-type="pmid">26035069</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B2">
        <label>2.</label>
        <citation-alternatives>
          <mixed-citation publication-type="journal">Lim, E.C.N., Yu, X.F. and Lim, C.E.D. (2025) Beyond Pharmaceuticals: Integrating Chinese Culinary Medicine with Modern Nutritional Science for Holistic Diabetes Management. <italic>Journal of Traditional Chinese Medical Sciences</italic>. https://doi.org/10.1016/j.jtcms.2025.08.003 <pub-id pub-id-type="doi">10.1016/j.jtcms.2025.08.003</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.jtcms.2025.08.003">https://doi.org/10.1016/j.jtcms.2025.08.003</ext-link></mixed-citation>
          <element-citation publication-type="journal">
            <person-group person-group-type="author">
              <string-name>Lim, E.C.N.</string-name>
              <string-name>Yu, X.F.</string-name>
              <string-name>Lim, C.E.D.</string-name>
            </person-group>
            <year>2025</year>
            <article-title>Beyond Pharmaceuticals: Integrating Chinese Culinary Medicine with Modern Nutritional Science for Holistic Diabetes Management</article-title>
            <pub-id pub-id-type="doi">10.1016/j.jtcms.2025.08.003</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B3">
        <label>3.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Macias-Navarro, L., McWhorter, J.W., Guevara, D.C., Bentley, S.S., Sharma, S.V., Torres, J.H., <italic>et al.</italic> (2024) A Virtual Culinary Medicine Intervention for Ethnically Diverse Individuals with Type 2 Diabetes: Development of the Nourishing the Community through Culinary Medicine. <italic>Frontiers in Nutrition</italic>, 11, Article 1383621. https://doi.org/10.3389/fnut.2024.1383621 <pub-id pub-id-type="doi">10.3389/fnut.2024.1383621</pub-id><pub-id pub-id-type="pmid">39221161</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fnut.2024.1383621">https://doi.org/10.3389/fnut.2024.1383621</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Macias-Navarro, L.</string-name>
              <string-name>McWhorter, J.W.</string-name>
              <string-name>Guevara, D.C.</string-name>
              <string-name>Bentley, S.S.</string-name>
              <string-name>Sharma, S.V.</string-name>
              <string-name>Torres, J.H.</string-name>
            </person-group>
            <year>2024</year>
            <article-title>A Virtual Culinary Medicine Intervention for Ethnically Diverse Individuals with Type 2 Diabetes: Development of the Nourishing the Community through Culinary Medicine</article-title>
            <source>Frontiers in Nutrition</source>
            <volume>11</volume>
            <elocation-id>1383621</elocation-id>
            <pub-id pub-id-type="doi">10.3389/fnut.2024.1383621</pub-id>
            <pub-id pub-id-type="pmid">39221161</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B4">
        <label>4.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Liu, J., Yao, C., Wang, Y., Zhao, J. and Luo, H. (2023) Non-Drug Interventions of Traditional Chinese Medicine in Preventing Type 2 Diabetes: A Review. <italic>Chinese Medicine</italic>, 18, Article No. 18. https://doi.org/10.1186/s13020-023-00854-1 <pub-id pub-id-type="doi">10.1186/s13020-023-00854-1</pub-id><pub-id pub-id-type="pmid">37964315</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1186/s13020-023-00854-1">https://doi.org/10.1186/s13020-023-00854-1</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Liu, J.</string-name>
              <string-name>Yao, C.</string-name>
              <string-name>Wang, Y.</string-name>
              <string-name>Zhao, J.</string-name>
              <string-name>Luo, H.</string-name>
            </person-group>
            <year>2023</year>
            <article-title>Non-Drug Interventions of Traditional Chinese Medicine in Preventing Type 2 Diabetes: A Review</article-title>
            <source>Chinese Medicine</source>
            <volume>18</volume>
            <elocation-id>No</elocation-id>
            <pub-id pub-id-type="doi">10.1186/s13020-023-00854-1</pub-id>
            <pub-id pub-id-type="pmid">37964315</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B5">
        <label>5.</label>
        <citation-alternatives>
          <mixed-citation publication-type="journal">Lim, E.C.N., Yu, W.T.S. and Lim, C.E.D. (2025) Integrative Gut Health: How Fermented Foods Bridge Ancient Eastern Wisdom and Modern Microbiome Science. <italic>Journal of Traditional Chinese Medical Sciences</italic>, 12, 499-508. https://doi.org/10.1016/j.jtcms.2025.07.002 <pub-id pub-id-type="doi">10.1016/j.jtcms.2025.07.002</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.jtcms.2025.07.002">https://doi.org/10.1016/j.jtcms.2025.07.002</ext-link></mixed-citation>
          <element-citation publication-type="journal">
            <person-group person-group-type="author">
              <string-name>Lim, E.C.N.</string-name>
              <string-name>Yu, W.T.S.</string-name>
              <string-name>Lim, C.E.D.</string-name>
            </person-group>
            <year>2025</year>
            <article-title>Integrative Gut Health: How Fermented Foods Bridge Ancient Eastern Wisdom and Modern Microbiome Science</article-title>
            <source>Journal of Traditional Chinese Medical Sciences</source>
            <volume>12</volume>
            <pub-id pub-id-type="doi">10.1016/j.jtcms.2025.07.002</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B6">
        <label>6.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Leeuwendaal, N.K., Stanton, C., O’Toole, P.W. and Beresford, T.P. (2022) Fermented Foods, Health and the Gut Microbiome. <italic>Nutrients</italic>, 14, Article 1527. https://doi.org/10.3390/nu14071527 <pub-id pub-id-type="doi">10.3390/nu14071527</pub-id><pub-id pub-id-type="pmid">35406140</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/nu14071527">https://doi.org/10.3390/nu14071527</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Leeuwendaal, N.K.</string-name>
              <string-name>Stanton, C.</string-name>
              <string-name>Toole, P.W.</string-name>
              <string-name>Beresford, T.P.</string-name>
              <string-name>Foods, H</string-name>
            </person-group>
            <year>2022</year>
            <article-title>Fermented Foods, Health and the Gut Microbiome</article-title>
            <source>Nutrients</source>
            <volume>14</volume>
            <elocation-id>1527</elocation-id>
            <pub-id pub-id-type="doi">10.3390/nu14071527</pub-id>
            <pub-id pub-id-type="pmid">35406140</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B7">
        <label>7.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Lim, E.C.N. and Lim, C.E.D. (2025) Microbiome-targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations. <italic>Acta</italic><italic>Microbiologica</italic><italic>Hellenica</italic>, 70, Article 36. https://doi.org/10.3390/amh70030036 <pub-id pub-id-type="doi">10.3390/amh70030036</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/amh70030036">https://doi.org/10.3390/amh70030036</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Lim, E.C.N.</string-name>
              <string-name>Lim, C.E.D.</string-name>
            </person-group>
            <year>2025</year>
            <article-title>Microbiome-targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations</article-title>
            <source>Acta Microbiologica Hellenica</source>
            <volume>70</volume>
            <elocation-id>36</elocation-id>
            <pub-id pub-id-type="doi">10.3390/amh70030036</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B8">
        <label>8.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Barra, M., Danino, T. and Garrido, D. (2020) Engineered Probiotics for Detection and Treatment of Inflammatory Intestinal Diseases. <italic>Frontiers in Bioengineering and Biotechnology</italic>, 8, Article 265. https://doi.org/10.3389/fbioe.2020.00265 <pub-id pub-id-type="doi">10.3389/fbioe.2020.00265</pub-id><pub-id pub-id-type="pmid">32296696</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fbioe.2020.00265">https://doi.org/10.3389/fbioe.2020.00265</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Barra, M.</string-name>
              <string-name>Danino, T.</string-name>
              <string-name>Garrido, D.</string-name>
            </person-group>
            <year>2020</year>
            <article-title>Engineered Probiotics for Detection and Treatment of Inflammatory Intestinal Diseases</article-title>
            <source>Frontiers in Bioengineering and Biotechnology</source>
            <volume>8</volume>
            <elocation-id>265</elocation-id>
            <pub-id pub-id-type="doi">10.3389/fbioe.2020.00265</pub-id>
            <pub-id pub-id-type="pmid">32296696</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B9">
        <label>9.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Gurunathan, S., Thangaraj, P. and Kim, J. (2023) Postbiotics: Functional Food Materials and Therapeutic Agents for Cancer, Diabetes, and Inflammatory Diseases. <italic>Foods</italic>, 13, Article 89. https://doi.org/10.3390/foods13010089 <pub-id pub-id-type="doi">10.3390/foods13010089</pub-id><pub-id pub-id-type="pmid">38201117</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/foods13010089">https://doi.org/10.3390/foods13010089</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Gurunathan, S.</string-name>
              <string-name>Thangaraj, P.</string-name>
              <string-name>Kim, J.</string-name>
              <string-name>Cancer, D</string-name>
            </person-group>
            <year>2023</year>
            <article-title>Postbiotics: Functional Food Materials and Therapeutic Agents for Cancer, Diabetes, and Inflammatory Diseases</article-title>
            <source>Foods</source>
            <volume>13</volume>
            <elocation-id>89</elocation-id>
            <pub-id pub-id-type="doi">10.3390/foods13010089</pub-id>
            <pub-id pub-id-type="pmid">38201117</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B10">
        <label>10.</label>
        <citation-alternatives>
          <mixed-citation publication-type="web">Food and Agriculture Organization of the United Nations (2025) Can Precision Fermentation Offer a Safe and Sustainable Future for Food Production? https://www.fao.org/food-safety/news/news-details/en/c/1735814</mixed-citation>
          <element-citation publication-type="web">
            <year>2025</year>
            <article-title>Can Precision Fermentation Offer a Safe and Sustainable Future for Food Production? https://www</article-title>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B11">
        <label>11.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Banerjee, S., Roy, P., Nandi, S. and Roy, S. (2023) Advanced Biotechnological Strategies Towards the Development of Crops with Enhanced Micronutrient Content. <italic>Plant Growth Regulation</italic>, 100, 355-371. https://doi.org/10.1007/s10725-023-00968-4 <pub-id pub-id-type="doi">10.1007/s10725-023-00968-4</pub-id><pub-id pub-id-type="pmid">36686885</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/s10725-023-00968-4">https://doi.org/10.1007/s10725-023-00968-4</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Banerjee, S.</string-name>
              <string-name>Roy, P.</string-name>
              <string-name>Nandi, S.</string-name>
              <string-name>Roy, S.</string-name>
            </person-group>
            <year>2023</year>
            <article-title>Advanced Biotechnological Strategies Towards the Development of Crops with Enhanced Micronutrient Content</article-title>
            <source>Plant Growth Regulation</source>
            <volume>100</volume>
            <pub-id pub-id-type="doi">10.1007/s10725-023-00968-4</pub-id>
            <pub-id pub-id-type="pmid">36686885</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B12">
        <label>12.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Dhiman, S., Kaur, S., Thakur, B., Singh, P. and Tripathi, M. (2025) Nutritional Enhancement of Plant-Based Fermented Foods: Microbial Innovations for a Sustainable Future. <italic>Fermentation</italic>, 11, Article 346. https://doi.org/10.3390/fermentation11060346 <pub-id pub-id-type="doi">10.3390/fermentation11060346</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/fermentation11060346">https://doi.org/10.3390/fermentation11060346</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Dhiman, S.</string-name>
              <string-name>Kaur, S.</string-name>
              <string-name>Thakur, B.</string-name>
              <string-name>Singh, P.</string-name>
              <string-name>Tripathi, M.</string-name>
            </person-group>
            <year>2025</year>
            <article-title>Nutritional Enhancement of Plant-Based Fermented Foods: Microbial Innovations for a Sustainable Future</article-title>
            <source>Fermentation</source>
            <volume>11</volume>
            <elocation-id>346</elocation-id>
            <pub-id pub-id-type="doi">10.3390/fermentation11060346</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B13">
        <label>13.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Qin, J., Kurt, E., LBassi, T., Sa, L. and Xie, D. (2023) Biotechnological Production of <italic>ω</italic>-3 Fatty Acids: Current Status and Future Perspectives. <italic>Frontiers in Microbiology</italic>, 14, Article 1280296. https://doi.org/10.3389/fmicb.2023.1280296 <pub-id pub-id-type="doi">10.3389/fmicb.2023.1280296</pub-id><pub-id pub-id-type="pmid">38029217</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2023.1280296">https://doi.org/10.3389/fmicb.2023.1280296</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Qin, J.</string-name>
              <string-name>Kurt, E.</string-name>
              <string-name>LBassi, T.</string-name>
              <string-name>Sa, L.</string-name>
              <string-name>Xie, D.</string-name>
            </person-group>
            <year>2023</year>
            <article-title>Biotechnological Production of ω-3 Fatty Acids: Current Status and Future Perspectives</article-title>
            <source>Frontiers in Microbiology</source>
            <volume>14</volume>
            <elocation-id>1280296</elocation-id>
            <pub-id pub-id-type="doi">10.3389/fmicb.2023.1280296</pub-id>
            <pub-id pub-id-type="pmid">38029217</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B14">
        <label>14.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Marcelli, A., Osimani, A. and Aquilanti, L. (2025) Vegetable By-Products from Industrial Processing: From Waste to Functional Ingredient through Fermentation. <italic>Foods</italic>, 14, Article 2704. https://doi.org/10.3390/foods14152704 <pub-id pub-id-type="doi">10.3390/foods14152704</pub-id><pub-id pub-id-type="pmid">40807640</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/foods14152704">https://doi.org/10.3390/foods14152704</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Marcelli, A.</string-name>
              <string-name>Osimani, A.</string-name>
              <string-name>Aquilanti, L.</string-name>
            </person-group>
            <year>2025</year>
            <article-title>Vegetable By-Products from Industrial Processing: From Waste to Functional Ingredient through Fermentation</article-title>
            <source>Foods</source>
            <volume>14</volume>
            <elocation-id>2704</elocation-id>
            <pub-id pub-id-type="doi">10.3390/foods14152704</pub-id>
            <pub-id pub-id-type="pmid">40807640</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B15">
        <label>15.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Monday, L., Tillotson, G. and Chopra, T. (2024) Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection—The Devil Is in the Details. <italic>Infec</italic><italic>tion and Drug Resistance</italic>, 17, 623-639. https://doi.org/10.2147/idr.s419243 <pub-id pub-id-type="doi">10.2147/idr.s419243</pub-id><pub-id pub-id-type="pmid">38375101</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.2147/idr.s419243">https://doi.org/10.2147/idr.s419243</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Monday, L.</string-name>
              <string-name>Tillotson, G.</string-name>
              <string-name>Chopra, T.</string-name>
            </person-group>
            <year>2024</year>
            <article-title>Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection—The Devil Is in the Details</article-title>
            <source>Infection and Drug Resistance</source>
            <volume>17</volume>
            <pub-id pub-id-type="doi">10.2147/idr.s419243</pub-id>
            <pub-id pub-id-type="pmid">38375101</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B16">
        <label>16.</label>
        <citation-alternatives>
          <mixed-citation publication-type="other">Wang, X., Sun, Z., Xue, H. and An, R. (2025) Artificial Intelligence Applications to Personalized Dietary Recommendations: A Systematic Review. <italic>Healthcare</italic>, 13, Article 1417. https://doi.org/10.3390/healthcare13121417 <pub-id pub-id-type="doi">10.3390/healthcare13121417</pub-id><pub-id pub-id-type="pmid">40565444</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3390/healthcare13121417">https://doi.org/10.3390/healthcare13121417</ext-link></mixed-citation>
          <element-citation publication-type="other">
            <person-group person-group-type="author">
              <string-name>Wang, X.</string-name>
              <string-name>Sun, Z.</string-name>
              <string-name>Xue, H.</string-name>
              <string-name>An, R.</string-name>
            </person-group>
            <year>2025</year>
            <article-title>Artificial Intelligence Applications to Personalized Dietary Recommendations: A Systematic Review</article-title>
            <source>Healthcare</source>
            <volume>13</volume>
            <elocation-id>1417</elocation-id>
            <pub-id pub-id-type="doi">10.3390/healthcare13121417</pub-id>
            <pub-id pub-id-type="pmid">40565444</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B17">
        <label>17.</label>
        <citation-alternatives>
          <mixed-citation publication-type="journal">Lim, E.C.N., Cheng, N.C.L. and Lim, C.E.D. (2025) The Art of Medical Synthesis: Where Chinese Medical Wisdom Intersects with Artificial Intelligence. <italic>Journal of Traditional Chinese Medical Sciences</italic>. https://doi.org/10.1016/j.jtcms.2025.08.001 <pub-id pub-id-type="doi">10.1016/j.jtcms.2025.08.001</pub-id><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.jtcms.2025.08.001">https://doi.org/10.1016/j.jtcms.2025.08.001</ext-link></mixed-citation>
          <element-citation publication-type="journal">
            <person-group person-group-type="author">
              <string-name>Lim, E.C.N.</string-name>
              <string-name>Cheng, N.C.L.</string-name>
              <string-name>Lim, C.E.D.</string-name>
            </person-group>
            <year>2025</year>
            <article-title>The Art of Medical Synthesis: Where Chinese Medical Wisdom Intersects with Artificial Intelligence</article-title>
            <pub-id pub-id-type="doi">10.1016/j.jtcms.2025.08.001</pub-id>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B18">
        <label>18.</label>
        <citation-alternatives>
          <mixed-citation publication-type="book">U.S. Food &amp; Drug Administration (2023) FDA Approves First Orally Administered Fecal Microbiota Product for the Prevention of Recurrence of Clostridioides Difficile Infection. https://www.fda.gov/news-events/press-announcements/fda-approves-first-orally-administered-fecal-microbiota-product-prevention-recurrence-clostridioides</mixed-citation>
          <element-citation publication-type="book">
            <year>2023</year>
            <article-title>FDA Approves First Orally Administered Fecal Microbiota Product for the Prevention of Recurrence of Clostridioides Difficile Infection</article-title>
          </element-citation>
        </citation-alternatives>
      </ref>
      <ref id="B19">
        <label>19.</label>
        <citation-alternatives>
          <mixed-citation publication-type="web">Seres Therapeutics (2023) VOWST Prescribing Information. Seres Therapeutics. https://www.vowst.com/prescribing-information</mixed-citation>
          <element-citation publication-type="web">
            <year>2023</year>
            <article-title>VOWST Prescribing Information</article-title>
          </element-citation>
        </citation-alternatives>
      </ref>
    </ref-list>
  </back>
</article>