1 Introduction

Engineered synthetic microbial communities (SynComs) are designed to mimic the natural microbiome of plants, but with enhanced capabilities to support plant health and productivity (Bu et al., 2024). These communities are constructed by selecting and combining microbial strains with known beneficial traits, such as antifungal activity, nutrient solubilization, and growth promotion (Souza et al., 2020; Wang et al., 2021; Yin et al., 2022). For instance, SynComs derived from rhizosphere soil have been shown to protect wheat against soilborne fungal pathogens, demonstrating their potential as biocontrol agents (Yin et al., 2022). Additionally, SynComs can be tailored to improve crop resilience under adverse environmental conditions, leveraging advances in microbial ecology and genetics (Souza et al., 2020).

The potential applications of SynComs in agriculture are vast. They can enhance nutrient efficiency and yield in crops like soybean by promoting root-associated microbial interactions (Wang et al., 2021; Song et al., 2024). Furthermore, SynComs can be designed to provide consistent beneficial outputs, such as disease suppression and growth promotion, by utilizing compost-derived microbial communities (Tsolakidou et al., 2018). The use of SynComs represents a promising strategy for sustainable agriculture, addressing challenges such as climate change, limited resources, and land degradation (Shayanthan et al., 2022).

The deployment of SynComs in agriculture necessitates a robust regulatory framework to ensure their safety and efficacy. The introduction of engineered microbial communities into the environment poses potential risks, including unintended ecological impacts and the horizontal transfer of genes among microbial populations (Martins et al., 2023). Therefore, it is crucial to establish guidelines and standards for the development, testing, and application of SynComs.

A regulatory framework would provide a structured approach to evaluate the safety of SynComs, considering factors such as microbial interactions, environmental persistence, and potential effects on non-target organisms (Vannier et al., 2019). It would also facilitate the monitoring and management of SynCom applications, ensuring that they deliver the intended benefits without compromising environmental and human health. By learning from global practices and existing regulatory models, we can develop a comprehensive framework that supports the safe and effective use of SynComs in agriculture.

By synthesizing findings from recent studies, this study aims to review the current state of SynCom research and applications in agriculture, highlight the potential benefits and challenges associated with SynComs, identify key components of a regulatory framework for SynComs, and propose guidelines for the development and application of SynComs. Based on the review and analysis, the study expect to suggest practical guidelines for researchers, policymakers, and practitioners to follow when developing and applying SynComs in agriculture.

2 Current Global Practices in SynCom Regulation

2.1 Overview of existing regulatory frameworks in different countries

The regulation of engineered synthetic microbial communities (SynComs) in agriculture varies significantly across the globe, reflecting diverse policy approaches, risk assessments, and regulatory priorities. While some countries have established comprehensive frameworks to address the unique challenges posed by SynComs, others are still in the nascent stages of developing their regulatory policies.

In the US, the regulation of SynComs falls under the purview of several agencies, including the Environmental Protection Agency (EPA), the United States Department of Agriculture (USDA), and the Food and Drug Administration (FDA). The Coordinated Framework for the Regulation of Biotechnology provides the overarching structure, emphasizing a case-by-case assessment based on the product's use and potential risks rather than the technology used to create it (Souza et al., 2020; Yin et al., 2022).

The EU employs a precautionary approach under its comprehensive regulatory framework for genetically modified organisms (GMOs). The European Food Safety Authority (EFSA) plays a central role in the risk assessment of SynComs, with a strong emphasis on environmental and human health safety. The EU’s regulatory framework is characterized by rigorous pre-market assessments and post-market monitoring requirements (Wang et al., 2021; Coker et al., 2022).

China’s regulatory framework for SynComs is evolving, with increasing focus on biotechnology and synthetic biology. The Ministry of Agriculture and Rural Affairs, along with other agencies, oversees the regulation of SynComs. The regulatory process includes stringent safety assessments and field trials before commercial release, reflecting China’s cautious approach to biotechnology (Shayanthan et al., 2022; Sai et al., 2022).

2.2 Case studies of SynCom regulation in major agricultural economies

United States: A notable example of SynCom regulation in the US is the approval process for a SynCom product designed to enhance nitrogen fixation in crops. Roper and Gupta (2016) mentioned that these products need to undergo extensive evaluation by the EPA for its environmental impact and by the USDA for its potential effects on agricultural practices. The collaborative regulatory approach ensured a thorough risk assessment, leading to conditional approval with specific monitoring requirements.

European Union: In the EU, a SynCom designed to improve soil health and crop resilience was subject to EFSA’s rigorous risk assessment process. The evaluation included comprehensive studies on environmental interactions, potential horizontal gene transfer, and impacts on non-target organisms (Urionabarrenetxea et al., 2022). The product will be approved under strict conditions, including continuous post-market environmental monitoring.

China: In China, the development of a SynCom aimed at enhancing rice productivity underwent a multi-stage regulatory process involving laboratory safety assessments, controlled field trials, and socio-economic impact evaluations to ensure compliance with national biosafety standards. Guo et al. (2017) valuated the effectiveness and safety of SynCom through field trials. These trials help in understanding the interactions of SynCom with the rice plants and the surrounding environment.

2.3 Comparative analysis of global regulatory approaches

A comparative analysis of global regulatory approaches to SynComs reveals several key themes and divergences:

1) Risk-based vs. precautionary approaches: The US adopts a risk-based approach, focusing on the specific characteristics and intended use of SynComs. In contrast, the EU’s precautionary approach involves more stringent pre-market assessments and ongoing monitoring to mitigate potential risks (Yin et al., 2022; Coker et al., 2022).

2) Regulatory coordination: In the US, multiple agencies collaborate under the Coordinated Framework for the Regulation of Biotechnology, ensuring that all aspects of SynCom safety are addressed. The EU centralizes its risk assessment through EFSA, promoting consistency and thoroughness (Wang et al., 2021; Yin et al., 2022). China’s regulatory system, while still developing, demonstrates a multi-agency approach with increasing integration and coordination (Shayanthan et al., 2022).

3) Public and environmental safety: All three regions prioritize public and environmental safety, though the methods and intensity of assessments vary. The US emphasizes adaptive management strategies post-approval, the EU focuses on extensive pre-market evaluations, and China incorporates both rigorous pre-release testing and post-market surveillance (Yin et al., 2022; Coker et al., 2022; Sai et al., 2022).

4) Innovation vs. regulation balance: Balancing innovation with regulation is a common challenge. The US framework is designed to facilitate innovation while ensuring safety, the EU’s stringent regulations can sometimes slow down the approval process, and China’s evolving framework seeks to strike a balance between encouraging biotechnological advancements and maintaining strict safety standards (Souza et al., 2020; Coker et al., 2022; Shayanthan et al., 2022).

Understanding these diverse regulatory practices provides valuable insights for developing a robust, globally informed regulatory framework for the safe integration of SynComs in agriculture. By learning from these global experiences, policymakers can create a harmonized approach that ensures safety, promotes innovation, and addresses the unique challenges of SynCom technology.

3 Key Components of an Effective Regulatory Framework

3.1 Risk assessment and management protocols

Risk assessment and management protocols are essential for the safe integration of engineered synthetic microbial communities (SynComs) in agriculture. These protocols should include comprehensive evaluations of potential risks associated with SynComs, such as their impact on non-target organisms, horizontal gene transfer, and environmental persistence. For instance, the dynamic nature of microbial communities and their ability to undergo horizontal gene transfer and mutations over time necessitates robust risk assessment frameworks to ensure long-term stability and safety (Souza et al., 2020; Martins et al., 2023). Additionally, the use of computational methods, including machine learning, can enhance the identification and mitigation of potential risks by predicting microbial interactions and their outcomes (Souza et al., 2020; Marín et al., 2021).

3.2 Safety standards and guidelines for SynCom development and deployment

Establishing safety standards and guidelines is crucial for the development and deployment of SynComs. These standards should address the selection of microbial strains, ensuring they possess beneficial traits without posing risks to plant health or the environment. For example, microbial traits such as biofilm formation, secondary metabolite production, and plant resistance induction should be carefully considered during SynCom design (Liu et al., 2019; Martins et al., 2023). Furthermore, guidelines should be developed for the consistent and reproducible assembly of SynComs, as variability in microbial community composition can affect their efficacy and safety (Tsolakidou et al., 2018; Coker et al., 2022). Standardized protocols for SynCom application, including dosage and delivery methods, should also be established to ensure uniformity and safety in agricultural practices.

3.3 Monitoring and compliance mechanisms

Effective monitoring and compliance mechanisms are necessary to ensure that SynComs are used safely and responsibly in agricultural settings. Continuous monitoring of SynCom performance and environmental impact is essential to detect any adverse effects promptly. For instance, high-resolution phenotyping and sequencing data can be integrated to monitor plant responses and microbial colonization dynamics, providing valuable insights into the effectiveness and safety of SynComs (Chai et al., 2021). Compliance mechanisms should include regular inspections, reporting requirements, and penalties for non-compliance to ensure adherence to established safety standards and guidelines. Additionally, the development of reproducible and tunable SynComs can facilitate consistent monitoring and compliance across different agricultural settings(Coker et al., 2022).

3.4 Public engagement and transparency

Public engagement and transparency are critical components of a regulatory framework for SynComs. Engaging with stakeholders, including farmers, researchers, and the general public, can build trust and acceptance of SynCom technologies. Transparent communication about the benefits, risks, and regulatory measures associated with SynComs can address public concerns and promote informed decision-making. For example, public engagement initiatives can highlight the potential of SynComs to enhance crop resilience and productivity while ensuring environmental sustainability (Souza et al., 2020; Pradhan et al., 2022). Additionally, involving stakeholders in the regulatory process can provide valuable feedback and improve the overall effectiveness of the regulatory framework.

By incorporating these key components, a regulatory framework can ensure the safe and effective integration of SynComs in agriculture, leveraging their potential to improve plant health and crop productivity while minimizing risks to the environment and human health.

4 Lessons from Global Practices

4.1 Successful strategies and best practices from various regulatory frameworks

Several countries have pioneered regulatory frameworks that successfully manage the integration of SynComs into agriculture. The United States, for example, through its Coordinated Framework for the Regulation of Biotechnology, has established clear pathways for the approval and monitoring of genetically engineered organisms, including SynComs. This framework emphasizes risk-based assessments, public transparency, and interagency coordination among the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the Department of Agriculture (USDA) (Schutte et al., 2017; Agathokleous et al., 2021).

Similarly, the European Union (EU) has implemented a comprehensive regulatory system under Directive 2001/18/EC and Regulation (EC) No 1829/2003, which governs the deliberate release and placing on the market of genetically modified organisms (GMOs). Additionally, the EU’s precautionary principle allows for a proactive approach in managing potential risks associated with SynComs (Silano and Silano, 2020).

China has implemented policies that encourage innovation and the development of SynComs. This includes providing funding for research and development, streamlining the approval process for field trials, and offering incentives for the commercialization of safe and effective SynComs (Shayanthan et al., 2022).

4.2 Challenges and limitations encountered in different regulatory environments

Despite the successes, various regulatory environments face challenges and limitations in integrating SynComs into agriculture. One significant challenge is the diversity in regulatory approaches and standards across different countries, leading to inconsistencies and trade barriers. Another limitation is the rapid pace of technological advancements in synthetic biology, which can outstrip the capacity of existing regulatory frameworks to adapt. Another major challenge is the inconsistent productivity of microbial inoculants due to varying environmental conditions, which affects the performance of individual microbes (Shayanthan et al., 2022). Additionally, the lack of standardized model microbial community systems and efficient approaches for building these communities has hindered the investigation and application of SynComs (Coker et al., 2022). These challenges highlight the need for more robust regulatory frameworks that can address these issues and support the large-scale application of SynComs in agriculture.

4.3 Insights from international collaborations and agreements

International collaborations and agreements have played a crucial role in advancing the research and application of SynComs in agriculture. Collaborative efforts have facilitated the sharing of knowledge and resources, leading to significant advancements in the field. For instance, the development of a model synthetic community of soil microorganisms that can be shared between research groups has demonstrated the importance of reproducibility and standardization in SynCom research (Coker et al., 2022). Furthermore, international collaborations have enabled the exploration of plant-disease-related microbes and the identification of specific microflora beneficial to plant health, which has contributed to the development of smart agriculture practices using SynComs (Wang et al., 2023). These insights underscore the importance of continued international cooperation to overcome the challenges and limitations associated with SynComs and to promote their safe and effective integration into agricultural practices.

5 Proposed Regulatory Framework for SynComs in Agriculture

5.1 Core principles and objectives

The core principles of the proposed regulatory framework for the integration of synthetic microbial communities (SynComs) in agriculture revolve around safety, efficacy, and sustainability. The primary objectives include:

1) Safety assurance: Ensuring that SynComs do not pose any risk to human health, non-target organisms, or the environment. This involves rigorous testing and monitoring of microbial interactions and potential horizontal gene transfer (Liu et al., 2019; Vannier et al., 2019; Martins et al., 2023).

2) Efficacy validation: Establishing standardized protocols to validate the effectiveness of SynComs in enhancing plant health, growth, and resilience under various environmental conditions (Souza et al., 2020; Wang et al., 2021; Yin et al., 2022).

3) Sustainability promotion: Encouraging the use of SynComs as a sustainable alternative to chemical fertilizers and pesticides, thereby reducing the environmental footprint of agricultural practices (Tsolakidou et al., 2018; Marín et al., 2021; Coker et al., 2022).

4) Transparency and traceability: Implementing measures to ensure transparency in the development, deployment, and monitoring of SynComs, including clear labeling and traceability of microbial strains used  (Vannier et al., 2019; Chai et al., 2021).

5.2 Structure and components of the proposed framework

The proposed regulatory framework is structured into several key components:

1) Regulatory oversight: Establishing a dedicated regulatory body responsible for overseeing the development, approval, and monitoring of SynComs. This body will set guidelines for safety and efficacy testing, as well as post-market surveillance (Liu et al., 2019; Vannier et al., 2019; Martins et al., 2023).

2) Standardized testing protocols: Developing standardized protocols for the assessment of SynComs, including in vitro and in planta tests to evaluate their impact on plant health and soil microbiome dynamics (Souza et al., 2020; Marín et al., 2021; Yin et al., 2022).

3) Risk assessment and management: Implementing comprehensive risk assessment procedures to identify and mitigate potential risks associated with SynComs, including their interactions with native microbial communities and potential for gene transfer (Liu et al., 2019; Vannier et al., 2019; Martins et al., 2023).

4) Data sharing and collaboration: Promoting data sharing and collaboration among researchers, industry stakeholders, and regulatory bodies to facilitate the continuous improvement of SynCom technologies and regulatory practices (Tsolakidou et al., 2018; Chai et al., 2021; Coker et al., 2022).

5) Public engagement and education: Engaging with the public and agricultural communities to raise awareness about the benefits and safety of SynComs, and to address any concerns or misconceptions (Vannier et al., 2019; Chai et al., 2021).

5.3 Implementation strategies and timeline

The implementation of the proposed regulatory framework will follow a phased approach:

Phase 1: Framework Development (Year 1-2)

1) Establish the regulatory body and develop initial guidelines and protocols for SynCom assessment.

2) Initiate pilot studies to test and refine standardized testing protocols and risk assessment procedures (Liu et al., 2019; Martins et al., 2023).

Phase 2: Pilot Testing and Refinement (Year 3-4)

1) Conduct extensive pilot testing of SynComs in diverse agricultural settings to validate safety and efficacy protocols.

2) Refine risk assessment and management strategies based on pilot study outcomes (Souza et al., 2020; Wang et al., 2021; Yin et al., 2022).

Phase 3: Full-scale Implementation (Year 5-6)

1) Roll out the regulatory framework for widespread adoption, including mandatory safety and efficacy testing for all SynCom products.

2) Establish a centralized database for tracking SynCom deployment and monitoring long-term impacts  (Tsolakidou et al., 2018; Coker et al., 2022).

Phase 4: Continuous Improvement (Year 7 and beyond)

1) Continuously update and improve the regulatory framework based on new scientific insights and technological advancements.

2) Foster ongoing collaboration and data sharing to enhance the effectiveness and safety of SynComs in agriculture (Tsolakidou et al., 2018; Chai et al., 2021; Coker et al., 2022).

By adhering to these principles, structure, and implementation strategies, the proposed regulatory framework aims to ensure the safe and effective integration of SynComs in agriculture, ultimately contributing to sustainable and resilient agricultural practices.

6 Risk Assessment and Management

6.1 Identification and evaluation of potential risks associated with SynComs

The integration of synthetic microbial communities (SynComs) in agriculture presents several potential risks that need to be carefully identified and evaluated. One primary concern is the unintended ecological impact that SynComs might have on native microbial communities and soil health. For instance, the introduction of SynComs could disrupt existing microbial balances, potentially leading to the suppression of beneficial native microbes or the proliferation of harmful pathogens (Yin et al., 2022; Shayanthan et al., 2022; Wang et al., 2023). Additionally, there is a risk of horizontal gene transfer between SynComs and native microbes, which could result in the spread of antibiotic resistance or other undesirable traits (Souza et al., 2020; Pradhan et al., 2022).

Another significant risk is the potential for SynComs to affect non-target plant species or other organisms within the ecosystem. This could lead to unforeseen consequences such as reduced biodiversity or the emergence of new pest and disease pressures (Wang et al., 2021; Sai et al., 2022). Furthermore, the stability and persistence of SynComs in various environmental conditions are not fully understood, raising concerns about their long-term effects and the possibility of SynComs becoming invasive (Arnault et al., 2023).

6.2 Mitigation strategies and contingency planning

To mitigate the risks associated with SynComs, several strategies can be employed. One approach is the careful selection and design of microbial strains used in SynComs to ensure they possess traits that minimize ecological disruption and enhance compatibility with native microbial communities (Souza et al., 2020; Shayanthan et al., 2022). This can be achieved through rigorous functional screening and the use of computational methods such as machine learning to predict and optimize microbial interactions (Liu et al., 2019; Souza et al., 2020).

Another important strategy is the implementation of containment measures to prevent the unintended spread of SynComs. This could involve physical barriers, such as controlled release systems, or biological containment strategies, such as the use of auxotrophic strains that require specific nutrients not found in the natural environment (Pradhan et al., 2022; Coker et al., 2022). Additionally, regular monitoring and assessment of SynComs’ impact on soil health, plant performance, and microbial diversity are crucial for early detection of any adverse effects and timely intervention (Yin et al., 2022).

Contingency planning is also essential to address potential failures or negative outcomes. This includes developing protocols for the rapid removal or neutralization of SynComs if they exhibit harmful behavior, as well as establishing communication channels with regulatory bodies and stakeholders to ensure coordinated responses (Sai et al., 2022; Arnault et al., 2023).

6.3 Case studies of risk management in SynCom applications

Several case studies highlight effective risk management practices in the application of SynComs. For example, Coker et al. (2022) has found that SynCom can be used in EcoFAB devices to repetitively study the interactions between rhizosphere plants and microorganisms. The development methods and workflow can easily be applied to the design and research of other model communities, and standardize microbiome research (Figure 1).

Figure 1 Community growth and composition with plant colonization in EcoFAB devices (Adopted from Coker et al., 2022) Image caption: (A) PCoA of the Bray-Curtis distances between the rhizosphere communities grown on plants for 7 days (n = 5 each) and the original inoculant (n = 1); (B) Relative abundance heat map of the starting inoculum and the rhizosphere communities grown on plants for 7 days (Adopted from Coker et al., 2022)

Coker et al. (2022) highlights the importance of monitoring microbial dynamics and environmental interactions in assessing the safety and efficacy of SynComs. Understanding how SynComs establish, persist, and interact with native communities is crucial for regulatory frameworks, ensuring ecological balance and mitigating potential risks in agricultural applications. The research underscores the need for rigorous testing and comprehensive risk assessments in the regulatory framework of SynComs.

Another study on the use of SynComs to protect wheat from soilborne fungal pathogens demonstrated the importance of selecting microbial strains with specific antifungal properties and monitoring their interactions with both the plant and native microbes (Figure 2) (Yin et al., 2022). This approach not only enhanced disease resistance but also minimized the risk of disrupting the native microbial community.

Figure 2 Effects of bacteria on wheat root rot caused by R. solani AG8 (Adopted from Yin et al., 2022) Image caption: (A) Single bacterial strain; (B) SynComs; (C) Wheat root rot scores; CK: Wheat grown in soil without bacteria and AG8 inoculation; CK1: AG8 only; CK2: AG8 and ddH2O; B5: AG8 and Pseudomonas sp. B5; B6: AG8 and Streptomyces sp. B6; B7: AG8 and Chryseobacterium sp. B7; B11: AG8 and Pseudomonas sp. B11; B12: AG8 and Pseudomonas sp. B12; B17: AG8 and Sphingomonas sp. B17; B20: AG8 and Cupriavidus campinensis B20; B27: AG8 and Asticcacaulis sp. B27; B43: AG8 and Rhodococcus erythropolis B43; BJ: AG8 and Janthinobacterium lividum BJ; P25: AG8 and Pseudomonas sp. P25; P38: AG8 and Chryseobacterium soldanellicola P38; P43: AG8 and Chryseobacterium sp. P43; P44: AG8 and Pedobacter sp. P44; C1: AG8 and SynCom 1; C2: AG8 and SynCom 2; C3: AG8 and SynCom 3; C4: AG8 and SynCom 4; C5: AG8 and SynCom 5; C6: AG8 and SynCom 6; C7: AG8 and SynCom 7; C8: AG8 and SynCom 8; C9: AG8 and SynCom 9; C10: AG8 and SynCom 10; The values are means ± SD; Different letters indicate significant differences (p ≤ 0.05, Tukey’s test, n = 10) (Adopted from Yin et al., 2022)

Yin et al. (2022) underscores the importance of rigorous screening and evaluation of microbial strains and SynComs for agricultural applications. Learning from this research can aid in establishing a regulatory framework that includes comprehensive risk assessment, efficacy testing, and environmental impact studies. Such a framework ensures the safe and effective integration of SynComs into agricultural practices, promoting plant health and productivity while minimizing potential risks.

There is also a case of evaluating the stability and effectiveness of SynComs under different environmental conditions through field experiments. Researchers used a functional screening process to identify beneficial root associated microbes and constructed SynComs (Wang et al., 2021) that significantly promote plant growth and nutrient acquisition, ensuring that the introduced microbes did not negatively impact the surrounding ecosystem.

These case studies illustrate the critical role of comprehensive risk assessment, strategic mitigation measures, and robust contingency planning in the safe and effective integration of SynComs in agriculture. By learning from these examples, we can develop a regulatory framework that ensures the benefits of SynComs are realized while minimizing potential risks.

7 Safety Standards and Guidelines

7.1 Criteria for assessing the safety and efficacy of SynComs

To ensure the safe and effective use of SynComs in agriculture, it is essential to establish clear criteria for their assessment. These criteria should include:

1) Microbial composition and functionality: The microbial strains included in SynComs should be well-characterized, with known beneficial traits such as plant growth promotion, nutrient acquisition, and disease resistance (Liu et al., 2019; Souza et al., 2020; Wang et al., 2021). The functionality of these strains should be validated through rigorous screening and selection processes (Vannier et al., 2019; Yin et al., 2022).

2) Host compatibility: SynComs should be compatible with the target crop species, ensuring that the microbial community can establish and persist in the plant rhizosphere without causing harm to the host plant (Coker et al., 2022).

3) Pathogenicity and toxicity: The potential pathogenicity and toxicity of SynComs to plants, animals, and humans should be thoroughly evaluated. This includes assessing the risk of horizontal gene transfer and the production of harmful metabolites (Sai et al., 2022; Martins et al., 2023).

4) Environmental stability: The stability and resilience of SynComs in various environmental conditions should be assessed to ensure consistent performance across different agricultural settings (Wang et al., 2021; Pradhan et al., 2022).

5) Regulatory compliance: SynComs should comply with existing regulatory frameworks and guidelines for the use of microbial inoculants in agriculture, including those related to genetically modified organisms (GMOs)  (Liu et al., 2019; Shayanthan et al., 2022).

7.2 Protocols for testing and validation

The development of standardized protocols for testing and validating SynComs is crucial for ensuring their safety and efficacy. These protocols should include:

1) In Vitro and In Vivo testing: Initial testing of SynComs should be conducted in controlled laboratory conditions (in Vivo) to evaluate their basic functionality and safety. This should be followed by field trials (in Vivo) to assess their performance in real-world agricultural settings (Yin et al., 2022; Coker et al., 2022).

2) Multi-Omics approaches: The use of multi-omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, can provide comprehensive insights into the interactions between SynComs and their host plants, as well as their impact on the surrounding environment (Vannier et al., 2019; Martins et al., 2023).

3) Long-term monitoring: Long-term monitoring of SynComs in the field is essential to assess their persistence, stability, and potential ecological impacts over time. This includes tracking changes in microbial community composition and function (Pradhan et al., 2022).

4) Risk Assessment Models: The development of risk assessment models can help predict the potential impacts of SynComs on plant health, soil microbiomes, and broader ecosystems. These models should be based on empirical data and validated through field studies (Sai et al., 2022).

7.3 Standards for environmental impact and biosafety

To minimize the potential risks associated with the use of SynComs in agriculture, it is important to establish standards for environmental impact and biosafety. These standards should include:

1) Ecological impact assessment: Comprehensive ecological impact assessments should be conducted to evaluate the potential effects of SynComs on soil health, native microbial communities, and non-target organisms (Shayanthan et al., 2022).

2) Containment and mitigation strategies: Strategies for containing and mitigating any unintended spread or adverse effects of SynComs should be developed. This includes measures for preventing the escape of engineered microbes into non-target environments (Sai et al., 2022; Martins et al., 2023).

3) Biosafety regulations: SynComs should adhere to national and international biosafety regulations, including those related to the release of genetically modified organisms (GMOs) and the use of microbial inoculants in agriculture (Pradhan et al., 2022).

4) Public and stakeholder engagement: Engaging with the public and relevant stakeholders is crucial for building trust and ensuring the responsible use of SynComs. This includes transparent communication of the benefits and risks associated with their use (Vannier et al., 2019; Shayanthan et al., 2022).

8 Monitoring and Compliance

8.1 Mechanisms for ongoing monitoring of SynCom performance and safety

Continuous monitoring of SynCom performance and safety is crucial to ensure their beneficial effects on crops and to mitigate any potential risks. Advanced computational methods, including machine learning and artificial intelligence, can be leveraged to screen and identify beneficial microbes, thereby improving the process of determining the best combination of microbes for desired plant phenotypes (Souza et al., 2020). Additionally, reproducible and tunable synthetic soil microbial communities have been developed, which can be used to monitor plant-soil microbe interactions under controlled conditions (Coker et al., 2022). These model communities allow for precise control of environmental conditions and easy measurement of plant-microbe metrics, facilitating ongoing monitoring efforts.

8.2 Reporting requirements and compliance checks

To ensure transparency and accountability, stringent reporting requirements and compliance checks must be established. Researchers and agricultural practitioners should be mandated to document and report the composition, application methods, and observed effects of SynComs on crops. This includes detailed records of microbial strains used, their interactions with host plants, and any environmental impacts observed. Field trials have demonstrated the importance of such documentation, as seen in studies where SynComs significantly promoted plant growth and nutrient acquisition (Wang et al., 2021). Regular compliance checks should be conducted to verify the accuracy of reported data and adherence to established guidelines.

8.3 Enforcement measures and penalties for non-compliance

Enforcement measures are essential to ensure adherence to regulatory standards and to address any instances of non-compliance. Penalties for non-compliance should be clearly defined and enforced to deter any deviations from established protocols. The development of SynComs involves integrating omics approaches with traditional techniques to manage biotic stresses in an eco-friendly manner (Pradhan et al., 2022). Any misuse or deviation from these practices should be met with appropriate penalties to maintain the integrity of SynCom applications. Additionally, the potential for SynComs to enhance crop resilience and productivity underscores the need for strict enforcement to prevent any adverse effects on agricultural ecosystems (Yin et al., 2022; Shayanthan et al., 2022).

9 Public Engagement and Transparency

9.1 Strategies for involving stakeholders in the regulatory process

Involving stakeholders in the regulatory process for the integration of engineered synthetic microbial communities (SynComs) in agriculture is crucial for ensuring the development of effective and accepted regulations. One effective strategy is to establish multi-stakeholder platforms that include farmers, scientists, policymakers, and industry representatives. These platforms can facilitate open dialogue and collaborative decision-making, ensuring that the perspectives and concerns of all stakeholders are considered (Souza et al., 2020; Coker et al., 2022). Additionally, conducting public consultations and workshops can help gather input from a broader audience, including local communities and non-governmental organizations (NGOs), thereby enhancing the inclusivity of the regulatory process (Pradhan et al., 2022).

9.2 Communication of risks and benefits to the public

Effective communication of the risks and benefits associated with SynComs is essential for public acceptance and informed decision-making. Clear and transparent communication strategies should be employed to convey scientific findings in an accessible manner. This includes the use of visual aids, infographics, and layman’s terms to explain complex scientific concepts (Wang et al., 2021; Yin et al., 2022; Arnault et al., 2023). Public outreach programs, such as community meetings and educational campaigns, can also play a significant role in disseminating information. It is important to highlight both the potential benefits, such as improved crop resilience and reduced dependency on chemical fertilizers, and the potential risks, including ecological impacts and unintended consequences, to provide a balanced view (Shayanthan et al., 2022; Wang et al., 2023).

9.3 Building public trust through transparency and accountability

Building public trust is fundamental to the successful integration of SynComs in agriculture. Transparency and accountability are key components in this process. Regulatory bodies should ensure that all stages of the regulatory process, from research and development to field trials and commercialization, are conducted transparently and with public oversight (Coker et al., 2022; Sai et al., 2022; Martins et al., 2023). This can be achieved by making all relevant data and findings publicly available and by providing regular updates on the progress and outcomes of SynCom-related projects. Additionally, establishing independent review panels and third-party audits can help ensure accountability and build public confidence in the regulatory framework (Pradhan et al., 2022; Wang et al., 2023).

By implementing these strategies, the regulatory process for SynComs can be made more inclusive, transparent, and trustworthy, ultimately facilitating their safe and effective integration into agricultural practices.

10 Future Directions and Recommendations

10.1 Emerging trends and future challenges in SynCom regulation

The field of synthetic microbial communities (SynComs) in agriculture is rapidly evolving, with several emerging trends and challenges that need to be addressed. One significant trend is the increasing use of computational methods, such as machine learning and artificial intelligence, to screen and identify beneficial microbes, thereby improving the process of determining the best combination of microbes for desired plant phenotypes (Souza et al., 2020). However, the regulatory framework must keep pace with these technological advancements to ensure the safe and effective use of SynComs.

Major challenge is the variability in SynCom performance due to differing environmental conditions, soil types, and crop varieties. This inconsistency can hinder the widespread adoption of SynComs in agriculture (Shayanthan et al., 2022). Additionally, the potential for horizontal gene transfer and retained mutations within SynComs poses a risk that needs to be carefully managed (Martins et al., 2023). Addressing these challenges requires a robust regulatory framework that can adapt to new scientific insights and technological innovations.

10.2 Recommendations for continuous improvement of the regulatory framework

To continuously improve the regulatory framework for SynComs, several recommendations can be made: 

1) There should be a focus on developing standardized protocols for the creation, testing, and application of SynComs. This includes guidelines for the functional screening of microbial strains and the assembly of SynComs based on specific plant needs (Wang et al., 2021; Pradhan et al., 2022).

2)  Regulatory bodies should encourage the use of reproducible and tunable model microbial communities, which can provide new insights into microbial ecology and help in the development of more effective SynComs (Coker et al., 2022). These models can serve as a basis for regulatory standards and facilitate the sharing of data and methodologies across research groups.

3) There should be an emphasis on long-term monitoring and assessment of SynComs in field conditions to ensure their stability and efficacy over time. This includes evaluating the impact of SynComs on plant health, soil microbiota, and the broader ecosystem (Yin et al., 2022; Arnault et al., 2023).

4) Fostering collaboration between researchers, industry stakeholders, and regulatory agencies is crucial for the continuous improvement of the regulatory framework. This collaboration can help in identifying potential risks, sharing best practices, and developing innovative solutions to emerging challenges (Wang et al., 2023).

10.3 Potential for international harmonization of SynCom regulations

The potential for international harmonization of SynCom regulations is significant, given the global nature of agricultural challenges and the need for sustainable solutions. Harmonized regulations can facilitate the global exchange of SynCom technologies and ensure that safety and efficacy standards are consistently met across different regions.

One approach to achieving harmonization is through the establishment of international guidelines and standards for SynCom development and application. These guidelines can be informed by the collective experiences and best practices from different countries (Shayanthan et al., 2022; Sai et al., 2022). International organizations, such as the Food and Agriculture Organization (FAO) and the International Organization for Standardization (ISO), can play a pivotal role in coordinating these efforts.

International collaboration in research and development can help in addressing region-specific challenges and in tailoring SynComs to diverse agricultural contexts. Sharing data and methodologies across borders can accelerate the development of effective SynComs and ensure their safe integration into agricultural practices worldwide (Pradhan et al., 2022).

11 Concluding Remarks

The integration of engineered synthetic microbial communities (SynComs) in agriculture holds significant promise for enhancing crop resilience, nutrient acquisition, and overall productivity. Research has demonstrated that SynComs can be tailored to promote plant growth and protect against pathogens by leveraging beneficial plant-microbe interactions. Advances in computational methods, such as machine learning, have further improved the screening and identification of beneficial microbes, facilitating the design of effective SynComs. Despite these advancements, challenges remain in ensuring the stability and reproducibility of SynComs in diverse agricultural settings.

For policymakers, the development of a regulatory framework for SynComs is crucial to ensure their safe and effective use in agriculture. This framework should address the potential risks associated with the release of engineered microbes into the environment and establish guidelines for their application. Researchers are encouraged to focus on understanding the mechanisms underlying plant-microbe interactions and the long-term stability of SynComs in various environmental conditions. Industry stakeholders should invest in the development and commercialization of SynCom-based products, ensuring that they are both effective and environmentally sustainable.

To fully realize the potential of SynComs in agriculture, a concerted effort is needed to develop and implement a robust regulatory framework. This framework should be informed by global best practices and include comprehensive risk assessments, standardized testing protocols, and clear guidelines for the commercialization and use of SynComs. Collaboration between policymakers, researchers, and industry stakeholders is essential to address the challenges and harness the benefits of SynComs for sustainable agriculture. By working together, we can ensure that SynComs contribute to a more resilient and productive agricultural system, ultimately supporting global food security and environmental sustainability.

Funding

This research was funded by a grant from The Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences.

Conflict of Interest Disclosure

The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

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