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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Fungal Biol.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Fungal Biology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Fungal Biol.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2673-6128</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/ffunb.2025.1641004</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Ecological dominance, functional roles, and biosafety of <italic>Trichoderma</italic> spp. as a biofertilizer fungus</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Win</surname><given-names>Thein Theint</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Bo</surname><given-names>Bo</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Khan</surname><given-names>Sikandar</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Fu</surname><given-names>Pengcheng</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>*</sup></xref>
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<aff id="aff1"><label>1</label><institution>Food Technology Center, Naypyitaw State Polytechnic University</institution>, <city>Naypyitaw</city>,&#xa0;<country country="mm">Myanmar</country></aff>
<aff id="aff2"><label>2</label><institution>Central Research Center, Yangon Technological University (YTU)</institution>, <city>Yangon</city>,&#xa0;<country country="mm">Myanmar</country></aff>
<aff id="aff3"><label>3</label><institution>Shaheed Benazir Bhutto University</institution>,&#xa0;<city>Sheringal</city>,&#xa0;<country country="pk">Pakistan</country></aff>
<aff id="aff4"><label>4</label><institution>State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University</institution>, <city>Haikou</city>, <state>Hainan</state>,&#xa0;<country country="cn">China</country></aff>
<author-notes>
<corresp id="c001"><label>*</label>Correspondence: Pengcheng Fu, <email xlink:href="mailto:pcfu@hainanu.edu.cn">pcfu@hainanu.edu.cn</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-01-12">
<day>12</day>
<month>01</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>6</volume>
<elocation-id>1641004</elocation-id>
<history>
<date date-type="received">
<day>04</day>
<month>06</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>28</day>
<month>11</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>28</day>
<month>11</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2026 Win, Bo, Khan and Fu.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Win, Bo, Khan and Fu</copyright-holder>
<license>
<ali:license_ref start_date="2026-01-12">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<p><italic>Trichoderma</italic> spp. are the most widely used fungal species in biofertilizers due to their capacity to enhance soil quality, suppress plant pathogens, and promote plant growth. However, due to the popularity of <italic>Trichoderma</italic> spp., usages in agricultural systems have raised significant environmental and safety concerns. This review mainly emphasizes the mechanisms that underlie the ecological dominance and competitive nature of <italic>Trichoderma</italic> spp. over native microbial communities and then explores the multifunctional role of <italic>Trichoderma</italic> spp. in soil ecosystems, which mainly focus on its interactions within the rhizosphere that influence dynamics plant&#x2013;microbe interactions and nutrient cycling. This article also highlights potential ecological imbalances associated with prolonged or repeated applications of <italic>Trichoderma</italic> spp. which include changes in soil microbial biodiversity and the decline of beneficial native microbiota. Furthermore, it evaluates the safety issues of <italic>Trichoderma</italic>-based biofertilizers by focusing their bioactive metabolites and potential effects on humans, animals, and non-target living things. Therefore, the review addresses the importance of site-specific application strategies, monitoring protocols, and comprehensive ecotoxicological assessments to mitigate unintended environmental and health concerns. By synthesizing recent findings and identifying key knowledge gaps, this work provides a framework for the responsible and sustainable integration of <italic>Trichoderma</italic> spp. into modern agroecological systems.</p>
</abstract>
<kwd-group>
<kwd>agro-ecological</kwd>
<kwd>bioactive</kwd>
<kwd>biofertilizer</kwd>
<kwd>ecotoxicological</kwd>
<kwd><italic>Trichoderma</italic> spp.</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was not received for this work and/or its publication.</funding-statement>
</funding-group>
<counts>
<fig-count count="2"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="60"/>
<page-count count="10"/>
<word-count count="4065"/>
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<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Fungal Secondary Metabolites and Mycotoxins</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>As sustainable agriculture becomes more widely recognized, microbial inoculants, especially fungal biofertilizers such as <italic>Trichoderma</italic> spp., have gained significant attention due to their multifunctional roles in promoting plant health, suppressing soil-borne pathogens, and enhancing nutrient bioavailability. They are initially characterized by their mycoparasitic and opportunistic plant-symbiotic behavior (<xref ref-type="bibr" rid="B50">Weindling, 1934</xref>; <xref ref-type="bibr" rid="B23">Howell, 2003</xref>; <xref ref-type="bibr" rid="B21">Harman, 2006</xref>). Therefore, <italic>Trichoderma</italic> spp. have been widely studied and commercialized as biocontrol agents and plant growth promoters (<xref ref-type="bibr" rid="B20">Harman, 2000</xref>; <xref ref-type="bibr" rid="B47">Vinale et&#xa0;al., 2008</xref>). In agricultural biotechnology, their genetic adaptability, rapid colonization ability, and capacity to synthesize diverse bioactive compounds have recognized <italic>Trichoderma</italic> spp. as one of the most well-documented fungal genera (<xref ref-type="bibr" rid="B36">Mukherjee et&#xa0;al., 2022</xref>).</p>
<p>Despite these benefits, the ecological consequences of <italic>Trichoderma</italic> spp. particularly in relation to their dominance mechanisms and interactions within complex soil microbial networks still remain underexplored. Amendment based on high-population single-species inoculants like <italic>Trichoderma</italic> spp., unlike microorganisms that have coevolved naturally within ecosystems, may disrupt long-term ecosystem functions, biodiversity resilience, and microbial balance (<xref ref-type="bibr" rid="B3">Barea et&#xa0;al., 2005</xref>). Their enhancement in fast nutrient uptake, production of antagonistic metabolites, and aggressive colonization of the rhizosphere may negatively impact native microbes involved in vital ecological processes such as organic matter decomposition, mycorrhizal symbiosis, and nitrogen fixation (<xref ref-type="bibr" rid="B39">Shahriar et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B2">Asghar et&#xa0;al., 2024</xref>).</p>
<p>Some <italic>Trichoderma</italic> spp. are compatible with beneficial soil organisms, whereas others can exert antagonistic effects, potentially disturbing microbial networks and altering the stability of soil trophic systems (<xref ref-type="bibr" rid="B33">McLean et&#xa0;al., 2014</xref>; <xref ref-type="bibr" rid="B32">Mac&#xed;as-Rodr&#xed;guez et&#xa0;al., 2020</xref>; <xref ref-type="bibr" rid="B59">Zhang et&#xa0;al., 2023</xref>). These dynamics necessitate a careful assessment of how <italic>Trichoderma</italic> spp.-based amendments impact soil microbial community compositions, surpass local fungi and bacteria, and impact soil enzymatic activities and biochemical cycles (<xref ref-type="bibr" rid="B39">Shahriar et&#xa0;al., 2022</xref>).</p>
<p>Human and animal health are also another safety issues that extend beyond soil ecology. <italic>Trichoderma</italic> spp. produce secondary metabolites which are generally regarded as safe including peptaibols, gliotoxins, and polyketides, which exhibit bioactivity and, in some cases, cytotoxicity. These compounds are essential for pathogen suppression; their persistence and effects on non-target organisms require more detailed studies, especially under field application (<xref ref-type="bibr" rid="B40">Sivasithamparam and Ghisalberti, 2002</xref>; <xref ref-type="bibr" rid="B55">Yao et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B18">Han et&#xa0;al., 2024</xref>).</p>
<p>This review mainly explores the ecological predominance of <italic>Trichoderma</italic> spp., assessing on their interactions with native microbial populations while highlighting biosafety issues related to their extensive use. By integrating the molecular biology perspective, soil science, and microbial ecology, this paper presents a balanced review of the opportunities and limitations of <italic>Trichoderma</italic> spp. in sustainable agriculture. It also warns the need for systematic application strategies that promote synergy rather than microbial monopolization; ensuring the long-term sustainability of soil ecosystems.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Ecological dominance and microbial interactions</title>
<p>The use of <italic>Trichoderma</italic> spp. as biocontrol agents and biofertilizers has gained much attention due to their effectiveness in promoting plant growth and suppressing phytopathogens. However, recent research evidence indicates that their ecological dominance can induce changes in native soil microbial communities. These alterations may result in microbial imbalances that negatively impact soil health and long-term ecosystem stability. A recent study by <xref ref-type="bibr" rid="B17">Gao et&#xa0;al. (2023)</xref> demonstrated that seed treatment with <italic>T. viride</italic> significantly reduced the disease index of soybean root rot while altering the microbial community structure in the rhizosphere. Notably, <italic>T. viride</italic> increased the complexity and stability of microbial co-occurrence networks which define the extent and level of interactions among different microbial taxa. Elevated network complexity commonly reflects stronger ecological interactions and greater community stability. On the other hand, <xref ref-type="bibr" rid="B43">Trabelsi and Mhamdi (2013)</xref> highlighted that even though such shifts may benefit plant health, this kind of microbial inoculation may also disrupt existing microbial interactions. <italic>Trichoderma</italic> spp. and other microbial inoculants generally promote soil microbial biomass; however, a meta-analysis of 335 independent studies indicated that these treatments significantly impact microbial community structure. In particular, they tend to simplify bacterial network complexity, thereby compromising the resilience of soil ecosystems (<xref ref-type="bibr" rid="B29">Li et&#xa0;al., 2024</xref>).</p>
<p>Moreover, <italic>Trichoderma</italic> spp. synthesize a variety of antimicrobial secondary metabolites, notably gliotoxins and peptaibols, each exhibiting distinct modes of action. Gliotoxins inhibit fungal growth by inducing oxidative stress and disrupting enzymatic activities, whereas peptaibols create ion-permeable channels in cellular membranes, resulting in cell death. Although these metabolites enhance pathogen suppression, they may also negatively impact non-target beneficial organisms and leading to reduced microbial diversity and altered community functions (<xref ref-type="bibr" rid="B39">Shahriar et&#xa0;al., 2022</xref>). Repeated applications of <italic>Trichoderma</italic> spp. have been shown to change the structure and functionality of indigenous microbial communities which lead to potential long-term consequences. Such disruptions can limit beneficial microbiota, deteriorate the nutrient cycling system, and reduce soil fertility (<xref ref-type="bibr" rid="B52">Xiong et&#xa0;al., 2017</xref>; <xref ref-type="bibr" rid="B31">Louren&#xe7;o et&#xa0;al., 2018</xref>). Meanwhile, inoculation with <italic>T. harzianum</italic> in sweet sorghum was found to increase the abundance of nitrogen-cycling genes, including those associated with nitrification and nitrogen fixation (<xref ref-type="bibr" rid="B49">Wei et&#xa0;al., 2023</xref>). This indicates a possible benefit in enhancing nutrient availability, while simultaneously highlighting the significant impact of <italic>Trichoderma</italic> spp. on soil microbial functionality. The increased expression of nitrogen-cycling genes indicates enhanced nitrogen mineralization and release into the rhizosphere, potentially leading to improved growth of crops and less demand on synthetic nitrogen fertilizers.</p>
<p>Field-based studies also report that <italic>Trichoderma</italic>-amended biofertilizers can significantly alter fungal communities, while exerting comparatively weaker effects on bacteria. This is likely because <italic>Trichoderma</italic> produces antifungal metabolites that target chitin-rich fungal cell walls, whereas bacteria possess peptidoglycan-dominated cell walls that are less responsive to these compounds. As these fungi are critical to nutrient cycling and plant health, such selective pressure may disrupt ecological balance (<xref ref-type="bibr" rid="B19">Hang et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B48">Wang et&#xa0;al., 2023</xref>). Up to this point, the long-term effects of <italic>Trichoderma</italic> spp. inoculation still remain unclear. Some studies report permanent alterations in microbial compositions, whereas others observed only temporary changes. Both of these study outcomes could affect key soil functions such as nitrogen fixation and organic matter decomposition (<xref ref-type="bibr" rid="B43">Trabelsi and Mhamdi, 2013</xref>).</p>
<p>Based on these findings, assessing the ecological risks of <italic>Trichoderma</italic> spp. applications is an emerging challenge to researchers. A balanced approach should consider their benefits in disease suppression and plant growth along with their influence on indigenous microbial populations. Alternative approaches such as utilizing native <italic>Trichoderma</italic> spp., monitoring microbial dynamics, and co-applying diverse microbial inoculants may help to mitigate ecological disturbances while enhancing sustainable soil health. Microbial shifts can be tracked using PCR-DGGE fingerprinting, qPCR-based quantification of key functional genes, 16S/ITS sequencing, metagenomics profiling, enzyme-linked functional assays, phospholipid fatty acid (PLFA) profiling, microbial respiration assays, etc., which provide insight into structural and functional changes in the soil community and allow for early detection of microbiome shifts.</p>
<p><xref ref-type="table" rid="T1"><bold>Table&#xa0;1</bold></xref> provides a comprehensive overview of key <italic>Trichoderma</italic> spp. used as biofertilizers and biocontrol agents, summarizing their major functional traits, ecological roles, and reported applications in agricultural systems. It highlights their diverse mechanisms of action, including mycoparasitism, induction of systemic resistance, nutrient solubilization, and production of growth-promoting metabolites while also listing target pathogens and crop systems where they have demonstrated efficacy. This tabulated information serves as a useful comparative reference for understanding the spectrum of <italic>Trichoderma</italic> activity and their potential utility under different agroecological conditions. Complementing this, <xref ref-type="fig" rid="f1"><bold>Figure&#xa0;1</bold></xref> illustrates the multifaceted interactions between <italic>Trichoderma</italic> spp., plants, pathogens, and the soil microbiome. It visually demonstrates how <italic>Trichoderma</italic> spp. colonizes the rhizosphere, suppresses pathogens through enzymatic degradation and secondary metabolites, enhances nutrient availability, and stimulates plant defense responses. Overall, readers can view <xref ref-type="fig" rid="f1"><bold>Figure&#xa0;1</bold></xref> as a simplified map showing how <italic>Trichoderma</italic> spp. strengthens plant growth by simultaneously improving nutrient access and weakening disease pressure. Together, <xref ref-type="table" rid="T1"><bold>Table&#xa0;1</bold></xref> and <xref ref-type="fig" rid="f1"><bold>Figure&#xa0;1</bold></xref> provide an integrated perspective on the functional versatility of <italic>Trichoderma</italic> spp., emphasizing both their practical benefits in sustainable agriculture and their broader ecological significance.</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Comparative ecological effects of <italic>Trichoderma</italic> spp. on soil microbial communities.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="middle" align="left">No.</th>
<th valign="middle" align="left"><italic>Trichoderma</italic> species</th>
<th valign="middle" align="left">Target microbial group</th>
<th valign="middle" align="left">Observed effect</th>
<th valign="middle" align="left">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left">1.</td>
<td valign="middle" align="left"><italic>T. viride</italic></td>
<td valign="middle" align="left">Rhizosphere bacteria</td>
<td valign="middle" align="left">Decreased diversity</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B17">Gao et&#xa0;al., 2023</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">2.</td>
<td valign="middle" align="left"><italic>T. harzianum</italic></td>
<td valign="middle" align="left">Nitrogen-fixing bacteria</td>
<td valign="middle" align="left">Increased nifH gene copy number</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B49">Wei et&#xa0;al., 2023</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">3.</td>
<td valign="middle" align="left"><italic>T. guizhouense</italic></td>
<td valign="middle" align="left">Fungal communities</td>
<td valign="middle" align="left">Reduced AMF germination</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B25">Islam et&#xa0;al., 2021</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">4.</td>
<td valign="middle" align="left"><italic>T. koningii</italic></td>
<td valign="middle" align="left">Soil fungi</td>
<td valign="middle" align="left">Suppression of pathogenic fungi</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B35">Monaco et&#xa0;al., 1991</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">5.</td>
<td valign="middle" align="left"><italic>T. atroviride</italic></td>
<td valign="middle" align="left">Soil fungi</td>
<td valign="middle" align="left">Mycoparasitism and competition</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B4">Ben&#xed;tez et&#xa0;al., 2004</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">6.</td>
<td valign="middle" align="left"><italic>T. longibrachiatum</italic></td>
<td valign="middle" align="left">Soil bacteria</td>
<td valign="middle" align="left">changes the composition of the soil bacterial and fungal communities</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B57">Yu et&#xa0;al., 2023</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">7.</td>
<td valign="middle" align="left"><italic>T. reesei</italic></td>
<td valign="middle" align="left">Cellulolytic microbes</td>
<td valign="middle" align="left">Competition for cellulose</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B14">Druzhinina and Kubicek, 2016</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">8.</td>
<td valign="middle" align="left"><italic>T. asperellum</italic></td>
<td valign="middle" align="left">Soil pathogens</td>
<td valign="middle" align="left">Biocontrol activity</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B58">Zapata-Sarmiento et&#xa0;al., 2020</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">9.</td>
<td valign="middle" align="left"><italic>T. virens</italic></td>
<td valign="middle" align="left">Rhizosphere microbes</td>
<td valign="middle" align="left">Modulation of microbial community</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B16">Fiorentino et&#xa0;al., 2018</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">10.</td>
<td valign="middle" align="left"><italic>T. pseudokoningii</italic></td>
<td valign="middle" align="left">Soil fungi</td>
<td valign="middle" align="left">Antagonism against pathogens</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B35">Monaco et&#xa0;al., 1991</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">11.</td>
<td valign="middle" align="left"><italic>T. harzianum</italic></td>
<td valign="middle" align="left">Various plant pathogens</td>
<td valign="middle" align="left">Modulates secondary metabolite production based on pathogen type</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B45">Vinale et&#xa0;al., 2009</xref>)</td>
</tr>
<tr>
<td valign="middle" align="left">12.</td>
<td valign="middle" align="left"><italic>T. harzianum, T. atroviride</italic></td>
<td valign="middle" align="left">Multiple phytopathogens</td>
<td valign="middle" align="left">Produces bioactive compounds with antifungal activity and ISR stimulation</td>
<td valign="middle" align="left">(<xref ref-type="bibr" rid="B46">Vinale et&#xa0;al., 2006</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Effect of <italic>Trichoderma</italic> spp. inoculation on agricultural production and soil ecosystem.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="ffunb-06-1641004-g001.tif">
<alt-text content-type="machine-generated">Diagram illustrating soil ecology and Trichoderma inoculation. Central theme focuses on enhanced agricultural productivity and sustainability in agroecosystems. Left side highlights biocontrol, induced systemic resistance, and nutrient bioavailability. Right side emphasizes microbial community shifts, nutrient cycling shifts, and biodiversity loss. Background shows soil processes like organic matter decomposition and nutrient absorption.</alt-text>
</graphic></fig>
</sec>
<sec id="s3">
<label>3</label>
<title>Biocontrol mechanisms and agroecological functions</title>
<p>The colonization of <italic>Trichoderma</italic> spp. at the rhizosphere, a dynamic zone of soil influenced by plant root exudates and microbial activities, is complex. These fungi exhibit both beneficial and potentially suppressive effects on native microbial communities. This dual behavior raises critical questions about whether <italic>Trichoderma</italic> spp.-based amendment applications support a sustainable balance between pathogen suppression and microbial symbiosis.</p>
<p>Controlled experiments and meta-analyses consistently demonstrate that <italic>Trichoderma</italic>-based formulations enhance nutrient uptake, increasing root biomass. They further demonstrate a consistent reduction in disease incidence across a wide range of crops (<xref ref-type="bibr" rid="B56">Yedidia et&#xa0;al., 2001</xref>; <xref ref-type="bibr" rid="B44">Verma et&#xa0;al., 2007</xref>). These effects are attributed to their induction of systemic resistance, production of phytohormones such as auxins and gibberellins, and solubilization of nutrients like phosphorus (<xref ref-type="bibr" rid="B8">Contreras-Cornejo et&#xa0;al., 2009</xref>).</p>
<p>According to anonymous studies, <italic>Trichoderma</italic> spp. enhance plant health through various mechanisms that have been well studied. They can secrete a wide range of bioactive secondary metabolites, including terpenoids and non-ribosomal peptides, which can stimulate plant growth and induce systemic resistance (ISR) to phytopathogens (<xref ref-type="bibr" rid="B9">Contreras-Cornejo et&#xa0;al., 2016</xref>; <xref ref-type="bibr" rid="B32">Mac&#xed;as-Rodr&#xed;guez et&#xa0;al., 2020</xref>). These fungi are also known for producing cell wall lytic enzymes and antifungal compounds, such as peptaibols and polyketides, which actively suppress soil borne diseases in the rhizosphere (<xref ref-type="bibr" rid="B47">Vinale et&#xa0;al., 2008</xref>).</p>
<p>In addition to phytopathogen suppression, <italic>Trichoderma</italic> spp. enhance nutrient availability by solubilizing phosphorus and producing siderophores that chelate iron, thereby enhancing plant nutrient uptake. Another significant beneficial trait of <italic>Trichoderma</italic> spp. is their ability to colonize root surfaces and form symbiotic-like associations. This kind of interactions may result in the secretion of growth-promoting substances, including indole-3-acetic acid (IAA), siderophores, and enzymes such as phosphatases and cellulases (<xref ref-type="bibr" rid="B22">Harman et&#xa0;al., 2004</xref>). Collectively, these mechanisms improve nutrient intake, root development, and resistance to abiotic stress.</p>
<p>However, the addition of <italic>Trichoderma</italic> spp. into the rhizosphere can also exert suppressive effects on non-target beneficial microbes. <xref ref-type="bibr" rid="B5">Brimner and Boland (2003)</xref> and <xref ref-type="bibr" rid="B25">Islam et&#xa0;al. (2021)</xref> published that certain <italic>Trichoderma</italic>-secreted metabolites have been shown to inhibit the germination of arbuscular mycorrhizal (AM) fungal spores, which are important for plant nutrient uptake, soil aggregation, and plant health. These adverse interactions suggest that whereas <italic>Trichoderma</italic> spp. can control harmful pathogens, they may also suppress beneficial microbial symbioses.</p>
<p>Outcomes of <italic>Trichoderma</italic> spp. application rarely remain consistent and depend on environmental factors such as soil chemistry, native microbial diversity, crop varieties, and climatic conditions. This dual nature of enhancing plant health while potentially disrupting microbial equilibrium highlights the significance of the research gap that must be addressed before commercial adoption for the application of <italic>Trichoderma</italic>-based biofertilizers. Thus, while <italic>Trichoderma</italic> spp. are promising tools for advancing sustainable agriculture, their introduction into soil ecosystems should be carefully monitored to preserve the functional balance of rhizospheric microbial communities.</p>
</sec>
<sec id="s4">
<label>4</label>
<title>Ecotoxicological aspects of <italic>Trichoderma</italic> spp.-based biofertilizers</title>
<p>While <italic>Trichoderma</italic> spp. offer considerable benefits as biocontrol agents and plant growth promoters, their potential to influence soil microbial networks and introduce ecotoxicity raises significant concerns regarding their long-term safety and environmental sustainability. These concerns are primarily linked to the production and environmental fate of their secondary metabolites, including gliotoxins, peptaibols, and polyketides.</p>
<p>Gliotoxins, produced notably by <italic>T. virens</italic>, are known for their strong antifungal and immunosuppressive properties. Although effective in pathogen control, gliotoxins have demonstrated cytotoxic effects on eukaryotic cells, raising safety concerns for non-target organisms. The environmental persistence of gliotoxin is influenced by soil pH, moisture, and microbial activity. For example, <xref ref-type="bibr" rid="B27">Jayalakshmi et&#xa0;al. (2021)</xref> found that gliotoxin remained stable in acidic soils with low microbial activities but degraded more rapidly in alkaline soils with robust microbial communities. These findings indicate that accumulation may occur in certain environments, raising concerns for soil biodiversity and long-term ecological stability. Therefore, risk assessment frameworks are necessary to ensure safe application of <italic>Trichoderma</italic>-based biofertilizers.</p>
<p>Peptaibols are linear, amphipathic peptides rich in &#x3b1;-aminoisobutyric acid (Aib), synthesized non-ribosomally by <italic>Trichoderma</italic> spp. These compounds integrate into cell membranes and form ion channels, leading to depolarization and cell death. Although compounds such as alamethicin and trichotoxins are highly effective against phytopathogens, their broad-spectrum mode of action may also affect non-target soil organisms, particularly arbuscular mycorrhizal fungi, plant-growth-promoting rhizobacteria (PGPR), nematodes, micro-arthropods, and even mammalian cells (<xref ref-type="bibr" rid="B11">Daniel and Rodrigues Filho, 2007</xref>; <xref ref-type="bibr" rid="B12">Das et&#xa0;al., 2018</xref>; <xref ref-type="bibr" rid="B10">Contreras-Cornejo et&#xa0;al., 2020</xref>). Soil stability and slow degradation may further promote bioaccumulation, leading to disruptions in microbial diversity and trophic interactions. Notably, the cytotoxic behavior of trichoguizaibols A&#x2013;L from <italic>T. guizhouense</italic> was demonstrated through controlled laboratory assays against human cancer cell lines rather than environmental exposure studies (<xref ref-type="bibr" rid="B18">Han et&#xa0;al., 2024</xref>). While this suggests potential biotechnological and pharmaceutical applications, it also raises ecological safety concerns, emphasizing the need for regulations and risk assessment in field release. Polyketides, synthesized through polyketide synthase (PKS) pathways, represent a major group of <italic>Trichoderma</italic>-derived secondary metabolites with wide structural and functional diversity. Compounds such as 6-pentyl-&#x3b1;-pyrone (6-PP), widely recognized for its strong antifungal activity, and harzianic acid, known to modulate plant root development while inhibiting competing microbes, illustrate this dual ecological role. Although these polyketides contribute to biocontrol by suppressing phytopathogens, their broad-spectrum toxicity may also affect beneficial organisms, including nitrogen-fixing bacteria and arbuscular mycorrhizal fungi. Furthermore, the persistence and potential bioaccumulation of polyketides in soil remain poorly resolved, particularly given the structural variability that can significantly alter toxicity and ecological impact (<xref ref-type="bibr" rid="B41">Szekeres et&#xa0;al., 2005</xref>; <xref ref-type="bibr" rid="B13">Degenkolb et&#xa0;al., 2008</xref>; <xref ref-type="bibr" rid="B6">Br&#xfc;ckner et&#xa0;al., 2009</xref>; <xref ref-type="bibr" rid="B34">Mikkola et&#xa0;al., 2012</xref>). These metabolites therefore enhance <italic>Trichoderma</italic> competitiveness but also highlight the need for ecotoxicological assessments and regulatory oversight to mitigate unintended effects in agricultural systems.&#x201d;</p>
<p>Polyketides, synthesized through polyketide synthase (PKS) pathways, represent a major group of <italic>Trichoderma</italic>-derived secondary metabolites with wide structural and functional diversity. Compounds such as 6-pentyl-&#x3b1;-pyrone (6-PP), widely recognized for its strong antifungal activity, and harzianic acid, known to modulate plant root development while inhibiting competing microbes, illustrate this dual ecological role. Although these polyketides contribute to biocontrol efficacy by inhibiting a range of plant pathogens, their broad-spectrum activity can negatively impact beneficial soil organisms, including nitrogen-fixing bacteria and mycorrhizal fungi. Furthermore, the long-term persistence and bioaccumulative potential of polyketides in soil ecosystems remain poorly understood, particularly given the structural variability that can significantly alter toxicity and ecological impact (<xref ref-type="bibr" rid="B41">Szekeres et&#xa0;al., 2005</xref>; <xref ref-type="bibr" rid="B13">Degenkolb et&#xa0;al., 2008</xref>; <xref ref-type="bibr" rid="B6">Br&#xfc;ckner et&#xa0;al., 2009</xref>; <xref ref-type="bibr" rid="B34">Mikkola et&#xa0;al., 2012</xref>). Collectively, these secondary metabolites play essential roles in the ecological competitiveness and efficacy of <italic>Trichoderma</italic> spp. in agricultural systems. However, their bioactivity also underscores the need for robust ecotoxicological evaluations. Regulatory frameworks must consider the persistence, mobility, and non-target effects of these compounds to ensure the safe use of <italic>Trichoderma</italic>-based biofertilizers.</p>
<p><xref ref-type="table" rid="T2"><bold>Table&#xa0;2</bold></xref> provides a summary of the major secondary metabolites produced by <italic>Trichoderma</italic> spp., their biological activities, and associated ecological concerns. Comprehensive ecotoxicological studies and risk assessment models are necessary to define safe application thresholds, environmental persistence timelines, and potential interactions with native microbiota.</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Secondary metabolites produced by <italic>Trichoderma</italic> species and the biological effects of respective metabolites.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="center">No.</th>
<th valign="top" align="center">Metabolite</th>
<th valign="top" align="center"><italic>Trichoderma</italic> species</th>
<th valign="top" align="center">Primary function</th>
<th valign="top" align="center">Ecotoxic/biosafety remark</th>
<th valign="top" align="center">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<th valign="top" colspan="6" align="left">I. Antifungal and antibacterial metabolites</th>
</tr>
<tr>
<td valign="top" align="left">1</td>
<td valign="top" align="left">Gliotoxin</td>
<td valign="top" align="left"><italic>T. virens</italic></td>
<td valign="top" align="center">Potent antifungal; suppresses competing soil fungi</td>
<td valign="top" align="left">Cytotoxic to mammalian and plant cells; requires dosage control in formulations</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B27">Jayalakshmi et&#xa0;al., 2021</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">2</td>
<td valign="top" align="left">Peptaibols</td>
<td valign="top" align="left"><italic>T. longibrachiatum</italic></td>
<td valign="top" align="center">Antimicrobial peptides forming transmembrane pores</td>
<td valign="top" align="left">May disrupt non-target cell membranes; toxicity depends on concentration</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B15">El-Nagar et&#xa0;al., 2024</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">3</td>
<td valign="top" align="left">Alamethicin</td>
<td valign="top" align="left"><italic>T. viride</italic></td>
<td valign="top" align="center">Antimicrobial peptide causing ion leakage</td>
<td valign="top" align="left">High membrane activity; could impact beneficial soil microbes</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B1">Aidemark et&#xa0;al., 2010</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">4</td>
<td valign="top" align="left">Trichothecene sesquiterpenes</td>
<td valign="top" align="left"><italic>T. cf. brevicompactum</italic></td>
<td valign="top" align="center">Antifungal secondary metabolites with high potency</td>
<td valign="top" align="left">Toxic to eukaryotic cells at elevated levels; monitoring advised</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B54">Yamazaki et&#xa0;al., 2020b</xref>)</td>
</tr>
<tr>
<th valign="top" colspan="6" align="left">II. Plant growth-promoting and signaling metabolites</th>
</tr>
<tr>
<td valign="top" align="left">5</td>
<td valign="top" align="left">Hydrocarbonated compound</td>
<td valign="top" align="left"><italic>T. atroviride</italic></td>
<td valign="top" align="center">Modulates root growth via ethylene and auxin signaling</td>
<td valign="top" align="left">Not fully assessed; possible hormonal imbalance in non-target plants</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B7">Contreras-Cornejo et&#xa0;al., 2015</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">6</td>
<td valign="top" align="left">6-Pentyl-&#x3b1;-pyrone (6-PP)</td>
<td valign="top" align="left"><italic>T. koningii</italic></td>
<td valign="top" align="center">Antifungal volatile; induces plant defense pathways</td>
<td valign="top" align="left">May alter rhizosphere microbial balance; eco-safe at low doses</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B26">Ismaiel and Ali, 2017</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">7</td>
<td valign="top" align="left">Harzianic acid</td>
<td valign="top" align="left"><italic>T. harzianum</italic></td>
<td valign="top" align="center">Metal chelation; promotes root health; detoxifies heavy metals</td>
<td valign="top" align="left">Low toxicity; suitable for bioremediation and sustainable formulations</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B42">Tommaso et&#xa0;al., 2021</xref>)</td>
</tr>
<tr>
<th valign="top" colspan="6" align="left">III. Cytotoxic and structural bioactive peptides</th>
</tr>
<tr>
<td valign="top" align="left">8</td>
<td valign="top" align="left">Epipolythiodiketopiperazines and trichothecene derivatives</td>
<td valign="top" align="left"><italic>T. cf. brevicompactum</italic></td>
<td valign="top" align="center">Cytotoxic and antimicrobial; involved in interspecies defense</td>
<td valign="top" align="left">High caution; trichothecene group compounds known for cytotoxicity</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B53">Yamazaki et&#xa0;al., 2020a</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">9</td>
<td valign="top" align="left">Trilongins</td>
<td valign="top" align="left"><italic>T. longibrachiatum</italic></td>
<td valign="top" align="center">Ion-channel&#x2013;forming peptides; cytotoxic</td>
<td valign="top" align="left">Disrupt mammalian cell membranes; dosage-dependent toxicity</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B34">Mikkola et&#xa0;al., 2012</xref>)</td>
</tr>
<tr>
<th valign="top" colspan="6" align="left">IV. Multifunctional and broad-spectrum compounds</th>
</tr>
<tr>
<td valign="top" align="left">10</td>
<td valign="top" align="left">Peptaibiotics</td>
<td valign="top" align="left"><italic>Trichoderma</italic> spp.</td>
<td valign="top" align="center">Antimicrobial peptides; suppress methanogens; enhance bioelectricity</td>
<td valign="top" align="left">May suppress beneficial anaerobic communities; impact limited to high concentrations</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">Ray et&#xa0;al., 2017</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">11</td>
<td valign="top" align="left">Multiple secondary metabolites (e.g., peptaibols, polyketides, terpenes)</td>
<td valign="top" align="left"><italic>Trichoderma</italic> spp.</td>
<td valign="top" align="center">Broad-spectrum antimicrobial and plant growth stimulation</td>
<td valign="top" align="left">May alter soil microbiota composition at high dosage</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">Keswani et&#xa0;al., 2014</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">12</td>
<td valign="top" align="left">Various secondary metabolites (e.g., viridins, diketopiperazines)</td>
<td valign="top" align="left"><italic>T. viride</italic> MM21</td>
<td valign="top" align="center">Antibacterial, antifungal, and anticancer activities</td>
<td valign="top" align="left">Cytotoxic to mammalian systems; formulation-dependent safety</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B38">Shaaban et&#xa0;al., 2023</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>This illustration of <xref ref-type="fig" rid="f2"><bold>Figure&#xa0;2</bold></xref> provides an extensive summary of <italic>Trichoderma</italic>&#x2019;s role as a metabolite hub, connecting biotic and abiotic environmental components. <italic>Trichoderma</italic> synthesizes antifungal and antibacterial agents, including gliotoxin, peptaibols, and alamethicin, which suppress infections and preserve microbial ecology. Additional metabolites such as 6-pentyl-&#x3b1;-pyrone and harzianic acid promote plant growth by improving root development and systemic resistance. Cytotoxic and structural peptides, such as trilongins and trichothecenes, help regulate interspecies defense mechanisms, promoting resilience within the soil microbiome. Abiotic metabolites, like harzianic acid and polyketides, promote heavy metal detoxification by chelating detrimental ions such as Pb<sup>2+</sup>, Cd<sup>2+</sup>, and Cu<sup>2+</sup>. Hydrocarbon compounds and peptides enhance plant stress resistance to drought and salinity. The ecotoxicological control and biosafety framework highlights its importance of monitoring and optimizing inoculant concentrations to prevent ecological disruption or toxicity. These activities collectively enhance sustainable agroecosystem management, improving soil health, crop yield, and environmental safety.</p>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>A conceptual model illustrating the interactions of Trichoderma secondary metabolites with both biotic and abiotic environments, and how these interactions support sustainable agricultural ecosystem management.</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="ffunb-06-1641004-g002.tif">
<alt-text content-type="machine-generated">Diagram illustrating the role of Trichoderma as a metabolite hub interacting with biotic and abiotic environments. The biotic environment includes plants, pathogens, and microbes, promoting functions like antifungal and antibacterial effects, plant growth, and cytotoxic peptide production. The abiotic environment involves metal detoxification and stress resistance enhancements. Trichoderma aids in ecotoxic control and biosafety, down to sustainable agroecosystem management.</alt-text>
</graphic></fig>
</sec>
<sec id="s5">
<label>5</label>
<title>Challenges, gaps, and future directions of trichoderma-based biofertilizers</title>
<p><italic>Trichoderma</italic> spp. are increasingly recognized for their dual roles in biocontrol and biofertilization. Their mechanisms of rhizosphere colonization, mycoparasitism, and secondary metabolite production contribute significantly to pathogen suppression and crop yield enhancement. Their use reduces dependence on chemical fertilizers and pesticides, enhances nutrient availability, and induces systemic resistance in plants, leading to improved yields and resilience under biotic and abiotic stress (<xref ref-type="bibr" rid="B22">Harman et&#xa0;al., 2004</xref>; <xref ref-type="bibr" rid="B30">Lorito et&#xa0;al., 2010</xref>). As their field applications become widespread globally, several critical challenges and research gaps must be addressed to ensure long-term sustainability and ecological safety regarding their ecological safety, the potential for resistance development, and potential challenges to microbial community dynamics. This highlights the importance of a comprehensive study of their long-term sustainability in agroecosystems.</p>
<p>One of the primary limitations of <italic>Trichoderma</italic>-based biofertilizers is their inconsistent efficacy under field conditions. Factors such as soil type, pH, moisture, temperature, and the composition of native microbial communities significantly influence colonization success and biological activity (<xref ref-type="bibr" rid="B24">Hoyos-Carvajal et&#xa0;al., 2009</xref>). Long-term sustainability and ecological safety, critical challenges, and research gaps must be addressed through field-based validation and by developing site-specific formulations and adaptive inoculation strategies for diverse agroecological conditions. However, emerging studies highlight potential ecological risks associated with high-dose applications or the introduction of non-native <italic>Trichoderma</italic> spp. Soil microcosm and field trials have reported reductions in native microbial diversity, particularly among fungi and bacteria that occupy similar ecological niches (<xref ref-type="bibr" rid="B60">Zin and Badaluddin, 2020</xref>). Factors such as competitive exclusion, rhizosphere acidification, and the secretion of broad-spectrum antifungal compounds appear to underlie these shifts, warranting further investigation into the resilience and functional redundancy of microbial communities following repeated inoculations. Extended use of <italic>Trichoderma</italic> spp. against the same pathogens can lead to reduced pathogen susceptibility, a phenomenon similar to pesticide resistance. Integrating <italic>Trichoderma</italic> spp. into broader integrated pest management (IPM) frameworks, rotating <italic>Trichoderma</italic> spp. across seasons, applying inoculants in mixed formulations, or co-inoculating with beneficial bacteria (PGPR) or mycorrhizal fungi, interval-based application scheduling, and formulating consortia that distribute ecological pressure across diverse taxa, rather than relying on one dominant strain to maintain rhizosphere diversity and soil stability, are some of the methods proposed.</p>
<p>Resistance development is another concern. While <italic>Trichoderma</italic> spp. primarily target pathogens with limited adaptability, instances of reduced pathogen susceptibility after prolonged exposure have been documented (<xref ref-type="bibr" rid="B51">Woo et&#xa0;al., 2014</xref>). This phenomenon parallels challenges observed with chemical pesticides and calls for integrated pest management strategies. Current formulation technologies face several challenges, including maintaining spore viability, ensuring acceptable shelf-life, and protecting bioactive compounds during storage and transport. Approaches such as encapsulation, improved carrier materials, and co-formulation with complementary microbes may greatly enhance stability and field performance. Future research must prioritize multi-omics approaches (genomics, metabolomics, transcriptomics, and proteomics) to unravel the molecular mechanisms such as PKS/NRPS gene clusters, chitinase and glucanase pathways, siderophore biosynthesis genes, and N-cycling regulators (e.g., nifH and amoA) that underlie <italic>Trichoderma</italic>&#x2019;s ecological interactions and functional roles. Additionally, long-term, multisite field trials are essential to assessing cumulative ecological impacts and developing best-practice guidelines for sustainable use. Regulatory frameworks should also emphasize the use of locally adapted strains, optimized dosage, and site-specific application protocols to minimize environmental risks.</p>
</sec>
<sec id="s6" sec-type="conclusion">
<label>6</label>
<title>Conclusion</title>
<p>In conclusion, while <italic>Trichoderma</italic>-based products offer promising tools for sustainable agriculture, offering positive impacts in biological control, nutrient cycling, and plant growth improvement, their widespread application prescribes a measured approach that balances agronomic advantages with ecological integrity. This review highlights the importance of a comprehensive evaluation of potential effects, such as unintentional alteration of native soil microbial communities and the ecological effects of bioactive metabolites. To guarantee safe and efficient application, long-term, multisite studies are essential to evaluating cumulative effects and interactions with native soil biota. The adoption of regulatory policies promoting the use of locally adapted strains, along with best practices for application timing and dosage, can help mitigate adverse impacts. Future research should incorporate ecological modeling alongside meta-omics platforms to decode how <italic>Trichoderma</italic> spp. regulate quorum-sensing circuits, MAP-kinase signaling cascades, oxidative stress-response genes, and root&#x2013;microbe communication pathways during field establishment. Comprehensive field validation across climate zones will be essential to verifying these molecular functions under real soil conditions. With continued monitoring, <italic>Trichoderma</italic>-based inoculants may support the transition to climate-resilient, ecologically stable agroecosystems while minimizing unintended microbial community shift.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="author-contributions">
<title>Author contributions</title>
<p>PF: Supervision, Writing &#x2013; review &amp; editing. TW: Conceptualization, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing, Resources, Visualization. BB: Formal Analysis, Writing &#x2013; original draft, Conceptualization. SK: Writing &#x2013; review &amp; editing, Resources.</p></sec>
<sec id="s9" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p></sec>
<sec id="s10" sec-type="ai-statement">
<title>Generative AI statement</title>
<p>The authors declared that generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p></sec>
<sec id="s11" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p></sec>
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<fn-group>
<fn id="n1" fn-type="custom" custom-type="edited-by">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/225327">T&#xfc;nde Pusztahelyi</ext-link>, University of Debrecen, Hungary</p></fn>
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<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/130824">Filomena De Leo</ext-link>, University of Messina, Italy</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1547355">Mehrdad Zarafshar</ext-link>, Linnaeus University, Sweden</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3100003">Pankaj Verma</ext-link>, IILM University, India</p></fn>
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