Microbial Bioactives

1. Introduction

Global agriculture is facing a mounting challenge. The world population, projected to exceed 9.8 billion by 2050, is driving an unprecedented demand for food, fiber, and bioenergy, requiring up to a 70% increase in crop productivity (Afridi et al., 2022). At the same time, crops are exposed to multifaceted environmental stresses, including drought, salinity, temperature extremes, and contamination by toxic heavy metals such as cadmium (Cd) (Sun et al., 2025; Shahzad et al., 2025). Among these stressors, Cd contamination poses a particularly insidious threat due to its high toxicity, non-essential nature, and propensity to accumulate in agricultural soils and food chains, ultimately endangering both crop productivity and human health (Clemens et al., 2013; He et al., 2020). The global prevalence of Cd in soils is predominantly linked to anthropogenic activities, including industrial emissions, mining operations, and the widespread application of phosphate fertilizers (Guo et al., 2018). Once absorbed by plants, Cd disrupts cellular homeostasis, induces oxidative stress, impairs photosynthetic machinery, damages chloroplast ultrastructure, alters nutrient and water uptake, and triggers DNA damage and programmed cell death (Chen et al., 2018; Sun et al., 2025). Consequently, Cd stress reduces both yield and crop quality, emphasizing the urgent need for effective mitigation strategies.

Plants have evolved intrinsic defense mechanisms to contend with Cd, which include exclusion (limiting Cd uptake at the root level), sequestration (binding and storing Cd within roots or vacuoles), and tolerance mechanisms involving the synthesis of chelators and antioxidants (Clemens et al., 2013; Nocito et al., 2007). However, the effectiveness of these defense strategies is intricately linked to the availability of essential nutrient elements, which can influence Cd mobility, uptake, and detoxification. In this context, nutrient-mediated interventions emerge as practical, eco-friendly, and physiologically relevant strategies for alleviating Cd toxicity in crops (Sun et al., 2025; Ma et al., 2024).

Complementing nutrient-based strategies, beneficial microbiota associated with crop plants (BMACP) represent a cornerstone of modern sustainable agriculture. These microbial communities—comprising bacteria and fungi inhabiting the rhizosphere, phyllosphere, and endosphere—have been increasingly recognized as the plant’s “second genome,” capable of modulating diverse aspects of plant growth, development, and resilience to environmental stressors (Tian et al., 2020b; Afridi et al., 2022). The integration of beneficial microbiota with targeted nutrient management offers a dual approach: microbial activity can enhance nutrient availability and uptake, while appropriate nutrient amendments can, in turn, modulate the structure and function of microbial communities to optimize Cd mitigation (Guo et al., 2018; Sun et al., 2025).

Plant Growth-Promoting Bacteria (PGPB) constitute a primary group within BMACP, encompassing symbiotic nitrogen-fixers like rhizobia and Frankia spp., as well as free-living genera such as Bacillus, Pseudomonas, and Enterobacter (Tian et al., 2020b; Lastochkina et al., 2019). These microbes confer multiple benefits, including the production of phytohormones (e.g., indole-3-acetic acid), ACC deaminase activity, phosphate solubilization, siderophore synthesis, and competitive exclusion of pathogens (Nagórska et al., 2007; Yedidia et al., 2001). Collectively, these functions not only enhance growth under normal conditions but also improve tolerance to Cd-induced stress by modulating nutrient uptake, antioxidant responses, and stress signaling pathways (Tian et al., 2020b; Shahzad et al., 2025).

Plant Growth-Promoting Fungi (PGPF) are equally significant. Trichoderma spp., Ganoderma spp., and arbuscular mycorrhizal fungi (AMFs) have been shown to improve nutrient acquisition and enhance plant resistance to heavy metals through mechanisms such as enhanced metal immobilization, induction of antioxidant enzyme systems, and competitive exclusion of pathogens (Stürmer & Bever, 2018; Manzar et al., 2022). AMFs, particularly, form symbiotic associations with roots that improve phosphorus uptake and facilitate the sequestration of metals such as Cd and arsenic in root tissues, effectively lowering their translocation to aerial parts of the plant (Cornejo et al., 2017; Spagnoletti et al., 2017). These findings underscore the importance of microbial consortia as both direct and indirect modulators of Cd stress tolerance in crops.

The interplay between BMACP and nutrient management is particularly evident in the mitigation of Cd stress. Microbial activity in the rhizosphere affects the phytoavailability of Cd by altering soil pH, releasing metal-binding compounds, and mobilizing or immobilizing nutrients that antagonize Cd uptake (Zhou et al., 2020; Zulfiqar et al., 2023). For instance, phosphate-solubilizing bacteria can increase the availability of phosphorus at the root surface, which in turn precipitates Cd as insoluble Cd-phosphate minerals, reducing its uptake by plants (Ma et al., 2024; Sun et al., 2025). Similarly, microbes that enhance zinc (Zn) bioavailability can competitively inhibit Cd uptake via shared transporters such as ZIP and IRT1, while simultaneously contributing to antioxidant defense through Zn-dependent enzymes like Cu/Zn-SOD (Cai et al., 2019; Sun et al., 2025). Iron (Fe) management follows a similar principle: Fe-siderophore-producing bacteria can mitigate Cd uptake by suppressing IRT1 expression and promoting Fe plaque formation on root surfaces, effectively immobilizing Cd in the rhizosphere (Xu et al., 2024; Wang et al., 2021). Sulfur (S) is another critical nutrient, as microbial and plant-assisted S assimilation enhances cysteine, glutathione (GSH), and phytochelatin (PC) synthesis, key chelators in Cd detoxification (Nocito et al., 2007; Sun et al., 2025).

Beyond these individual nutrient effects, the synergistic interactions among multiple nutrients and microbiota can further optimize Cd mitigation. Calcium (Ca$^{2+}$) competes with Cd$^{2+}$ for cell wall and transporter binding sites, while manganese (Mn) and silicon (Si) fortify antioxidant defenses and physical barriers, respectively, and their bioavailability can be enhanced by specific microbial activity (Dong et al., 2022; Huang et al., 2017; Wang et al., 2013). Nitrogen (N) also plays a nuanced role: nitrate-based fertilization alkalinizes the rhizosphere, decreasing Cd solubility, whereas ammonium can increase Cd mobility, highlighting the importance of form-specific nutrient strategies that are often influenced by microbial metabolism (Huang et al., 2019).

Recent systematic reviews and meta-analyses support the notion that BMACP, in conjunction with nutrient management, offers a practical, sustainable, and eco-friendly solution to Cd stress (Tian et al., 2020b; Sun et al., 2025; Ma et al., 2024). Studies consistently show that microbial consortia, when coupled with strategic nutrient amendments, can reduce Cd accumulation in edible tissues, enhance growth, and improve antioxidant capacity across various crops, including rice, wheat, and maize (Shahzad et al., 2025; Zulfiqar et al., 2023). These findings also highlight the importance of tailoring interventions to specific soil types, crop species, and local microbial communities to achieve optimal Cd mitigation outcomes (Guo et al., 2018).

Despite these advances, several challenges remain. The mechanisms underlying microbe-nutrient-Cd interactions are complex and context-dependent, influenced by soil chemistry, plant genotype, environmental conditions, and microbial diversity (Tian et al., 2017; Guo et al., 2018). Additionally, while laboratory and greenhouse studies demonstrate clear benefits, field-level validation under variable agronomic conditions is limited, necessitating more large-scale, multi-location trials. Integrating “omics” approaches, including metagenomics, transcriptomics, and metabolomics, with nutrient and microbial analyses may provide deeper mechanistic insights and inform precision strategies for Cd stress mitigation (Afridi et al., 2022; Tian et al., 2020b).

In summary, the evidence from systematic reviews and meta-analytical studies indicates that beneficial microbiota associated with crop plants, when strategically integrated with nutrient-mediated interventions, can play a pivotal role in alleviating Cd stress. By enhancing nutrient uptake, modulating Cd mobility, and inducing stress-responsive mechanisms, these approaches offer a holistic, sustainable, and environmentally sound alternative to conventional chemical remediation strategies. Understanding the intricate interactions among microbes, nutrients, and Cd dynamics is critical for designing future agricultural practices that ensure crop productivity, food safety, and ecological resilience (Sun et al., 2025; Afridi et al., 2022). The convergence of microbial ecology and nutrient science thus represents a frontier in sustainable crop management, promising to address one of the most pressing challenges in modern agriculture.

2. Materials and Methods

This study was conducted as a systematic review and meta-analysis to investigate the effects of beneficial microbiota associated with crop plants and nutrient-mediated interventions on alleviating cadmium stress. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Figure 1) to ensure transparency and reproducibility. A comprehensive and structured approach was employed, integrating published peer-reviewed articles, reviews, and experimental studies that evaluated microbial and nutrient-mediated strategies in crops exposed to cadmium stress. The study selection process followed PRISMA guidelines and is summarized in Figure 1

A systematic literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases for articles published until December 2025. The search strategy combined keywords and MeSH terms to capture studies on beneficial microbiota, nutrients, and cadmium stress in plants. The primary search terms included “beneficial microbiota” or “plant growth-promoting bacteria” or “arbuscular mycorrhizal fungi” or “PGPB” or “PGPF” and “cadmium stress” or “heavy metal stress” or “Cd toxicity” and “nutrient-mediated alleviation” or “micronutrients” or “macronutrients” or “phosphate” or “sulfur” or “zinc” or “iron” or “calcium” and “crop plants” or “wheat” or “rice” or “maize” or “vegetables.” Boolean operators, truncations, and wildcards were applied to enhance search sensitivity. Additional studies were identified through manual screening of references from relevant reviews and articles. Duplicate publications were removed using EndNote X9 software to ensure a unique dataset.

Studies were screened according to pre-defined eligibility criteria based on the PICO framework. The population included all studies involving crop plants exposed to cadmium stress, encompassing both monocotyledonous and dicotyledonous species. The interventions included the role of beneficial microbes, nutrient-mediated strategies, or their synergistic combinations in mitigating cadmium stress, including inoculation with plant growth-promoting bacteria, arbuscular mycorrhizal fungi, Trichoderma species, and nutrient amendments. The comparator included control plants without microbial inoculation or nutrient supplementation under similar cadmium stress conditions. The outcomes included quantitative or qualitative data on cadmium accumulation, plant growth, biomass, nutrient uptake, antioxidant enzyme activity, photosynthetic efficiency, and stress markers. Studies not in English, lacking primary experimental data, conducted on non-plant systems or purely hydroponic conditions, or missing quantitative outcomes were excluded. Screening was performed in two stages: title and abstract screening followed by full-text evaluation. Discrepancies were resolved through consensus between two independent reviewers, with a third reviewer consulted if necessary.

Data extraction was conducted using a standardized sheet in Microsoft Excel 2021 to ensure consistency. The extracted information included bibliographic details such as author, year, journal, and country; plant species, cultivar, growth stage, and experimental conditions; cadmium exposure, including source, concentration, and duration; microbial intervention details including species, inoculation method, dose, and frequency; nutrient intervention details including type, concentration, application method, and treatment duration; measured outcomes including plant height, root and shoot biomass, chlorophyll content, nutrient uptake, cadmium content in roots and shoots, antioxidant enzyme activity, photosynthetic efficiency, and stress markers; and experimental design details including number of replicates, control groups, and statistical analyses reported. Extracted data were carefully checked for accuracy, and missing values were requested from corresponding authors when available.

The methodological quality of included studies was assessed using a modified Cochrane Risk of Bias tool adapted for plant-based experiments. The parameters evaluated included randomization of experimental units, presence of control groups, adequacy of replication, blinding during measurements, and completeness of outcome reporting. Studies were categorized as low, medium, or high risk of bias, and only low and medium risk studies were included in the meta-analysis to minimize bias.

For the meta-analysis, studies reporting continuous outcomes were included. Effect sizes were calculated using Hedges’ g or mean differences with 95% confidence intervals. Heterogeneity was assessed using Cochran’s Q test and quantified with the I² statistic, with values greater than 50 percent considered substantial. Random-effects models were applied to account for between-study variation. Subgroup analyses were performed based on plant type, microbial type, nutrient type, and cadmium exposure level. Publication bias was assessed using funnel plots, Egger’s regression test, and the trim-and-fill method, and sensitivity analyses were conducted by sequentially excluding individual studies to evaluate robustness of pooled results.

Data from studies reporting outcomes in different units were standardized for comparability. Cadmium concentrations were converted to milligrams per kilogram dry weight, nutrient concentrations to milligrams per kilogram or micrograms per gram, and enzyme activities to units per gram fresh or dry weight. Log-transformation was applied to normalize skewed distributions, particularly for cadmium accumulation and antioxidant enzyme activity.

Statistical analyses were performed using R software (version 4.3.1) with meta, metafor, dmetar, ggplot2, and forestplot packages for meta-analysis, effect size calculation, sensitivity analyses, and visualization of results. Figures, forest plots, and funnel plots were generated to illustrate effect sizes, heterogeneity, and subgroup comparisons.

Ethical considerations were addressed, and as this study relied solely on published data, no ethical approval was required. Efforts were made to accurately represent original data and acknowledge original authors. Limitations inherent to the available literature were recognized, including variability in experimental conditions such as soil type, cadmium source, and plant cultivar, inconsistency in reporting microbial inoculation and nutrient application methods, predominance of short-term or pot-based experiments limiting field extrapolation, and potential publication bias favoring positive outcomes.

3. Results

3.1 Interpretation of funnel and forest plots

The forest and funnel plots provide complementary insights into the efficacy of microbial inoculation and nutrient-mediated interventions in mitigating cadmium stress in plants. The forest plot (Figure 2) summarizes the effect sizes (Hedges’ g) of individual studies on shoot biomass, allowing visual assessment of both magnitude and consistency of treatment effects. Across the 42 studies included in the meta-analysis, most effect sizes are positive, indicating that microbial inoculation consistently enhances plant growth under cadmium stress. The pooled effect size for shoot biomass was 1.02 (95% CI: 0.78–1.26), which is substantial and statistically significant, reflecting a strong overall impact. Subgroup analyses within the forest plot further demonstrate differential responses based on microbial type. Arbuscular mycorrhizal fungi (AMF) treatments generally produced larger effect sizes compared to plant growth-promoting bacteria (PGPB), suggesting that AMF may be particularly effective in facilitating nutrient uptake and mitigating metal toxicity in aerial tissues. The forest plot also illustrates heterogeneity among studies, with some confidence intervals crossing zero, indicating limited or non-significant effects in certain experimental contexts. This heterogeneity likely arises from differences in plant species, microbial strains, nutrient regimes, soil type, and cadmium concentrations. Synergistic effects of combined microbial and nutrient interventions on cadmium mitigation are illustrated in Figure 2.

The funnel plot serves as a diagnostic tool for potential publication bias or small-study effects. In an ideal scenario with no bias, studies are symmetrically distributed around the pooled effect size, forming an inverted funnel shape. In this analysis, the funnel plot displayed mild asymmetry, with a slightly higher concentration of small-sample studies showing larger positive effects. This suggests that smaller studies with significant results may be preferentially published, a common issue in environmental and agricultural research. Nevertheless, Egger’s regression test yielded a p-value of 0.08, which is above the conventional significance threshold, indicating that the observed asymmetry may not substantially distort the overall conclusions. Sensitivity analysis, in which individual studies were sequentially removed, further confirmed the robustness of the pooled effect size, suggesting that no single study disproportionately influenced the meta-analytic outcomes.

Together, the forest and funnel plots provide a comprehensive view of both efficacy and reliability of the interventions. The forest plot confirms that microbial inoculation and nutrient supplementation generally produce positive and meaningful improvements in plant growth under cadmium stress. It highlights the consistency of these effects across diverse experimental conditions while acknowledging natural variability. The funnel plot, on the other hand, addresses the potential for bias, indicating that although minor asymmetry exists, the conclusions remain largely valid. These visual and statistical analyses underscore the importance of integrating multiple studies to obtain a generalized understanding of treatment effectiveness. Furthermore, the plots emphasize the value of considering study design, sample size, and experimental heterogeneity when interpreting meta-analytic results. In practice, this means that while microbial and nutrient strategies are broadly effective, their implementation may need to be tailored to specific crops, soil conditions, and cadmium contamination levels to maximize efficacy.

3.2 Meta-Analytic Evidence for Microbial and Nutrient Strategies Mitigating Cadmium Stress in Crops

The compiled data from 42 eligible studies provided a comprehensive overview of the effects of beneficial microbiota and nutrient-mediated interventions on crop plants under cadmium stress. Descriptive statistics indicate that microbial inoculation alone significantly improved plant growth parameters compared to untreated controls. Mean shoot biomass increased by 23.5% (SD = 7.8) in inoculated plants, while root biomass exhibited an average enhancement of 18.9% (SD = 6.5). The observed variability across studies reflects differences in plant species, microbial strains, and experimental conditions, which was further assessed through meta-analytic techniques.

Meta-analysis revealed a pooled effect size (Hedges’ g) of 1.02 (95% CI: 0.78–1.26) for shoot biomass and 0.87 (95% CI: 0.63–1.11) for root biomass, indicating strong positive impacts of microbial interventions on plant growth under cadmium stress. Heterogeneity among studies was substantial (I² = 62% for shoot biomass and I² = 58% for root biomass), suggesting variability attributable to both biological and methodological factors. Subgroup analysis demonstrated that inoculation with arbuscular mycorrhizal fungi resulted in the highest increase in shoot biomass (Hedges’ g = 1.18), whereas PGPB-mediated treatments were more effective in improving root biomass (Hedges’ g = 0.95).

Nutrient-mediated interventions, including supplementation with macronutrients (N, P, K) and micronutrients (Zn, Fe, Ca), significantly mitigated cadmium toxicity. The general characteristics of the 42 studies included in the meta-analysis are summarized in Table 1. Plants receiving Zn and P supplementation exhibited a 28.6% reduction in shoot cadmium content compared to untreated controls (p < 0.01), whereas root cadmium content decreased by 21.4% (p < 0.05). Combined microbial and nutrient interventions produced synergistic effects, with the most pronounced reduction in cadmium translocation observed when PGPB inoculation was paired with Zn application.

Table 1. Characteristics of studies included in the meta-analysis on microbial and nutrient-mediated mitigation of cadmium stress in crops
This table summarizes the key characteristics of the 42 studies included in the meta-analysis, including crop species, microbial inoculants, nutrient interventions, cadmium concentrations, experimental conditions, and primary response variables. It provides the contextual foundation for interpreting pooled effect sizes and heterogeneity.

Photosynthetic efficiency, measured as Fv/Fm, was consistently higher in treated plants, with a mean improvement of 0.07 units over controls (p < 0.01). Similarly, antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were significantly elevated in response to microbial inoculation and nutrient supplementation. The pooled SOD activity effect size was 0.92 (95% CI: 0.68–1.16), while CAT and POD activities demonstrated effect sizes of 0.81 and 0.86, respectively. These findings indicate enhanced oxidative stress mitigation, aligning with previous reports highlighting microbial and nutrient modulation of plant defense systems under heavy metal stress (Ahmad et al., 2021; Chen et al., 2020). Nutrient-mediated reductions in cadmium accumulation in roots and shoots across studies are summarized in Table 2.

Table 2. Effects of nutrient-mediated interventions on cadmium accumulation in crop roots and shoots
This table presents pooled and study-level evidence on the effects of macro- and micronutrient supplementation on cadmium accumulation in crop roots and shoots. The data highlight nutrient-specific reductions in cadmium uptake and translocation under stress conditions.

Sensitivity analysis confirmed the robustness of results, with exclusion of individual studies yielding negligible changes in pooled effect sizes (<5%). Funnel plots indicated slight asymmetry for root biomass outcomes, suggesting potential publication bias; however, Egger’s regression test did not reach statistical significance (p = 0.08), indicating that the overall conclusions are unlikely to be substantially affected by bias.

Correlation analysis between cadmium accumulation and nutrient uptake revealed a negative association (r = –0.62, p < 0.01), confirming that nutrient supplementation enhances cadmium sequestration in roots while limiting translocation to shoots. Subgroup analysis by plant species indicated that cereals, particularly rice and wheat, responded more favorably to combined microbial and nutrient treatments compared to legumes and leafy vegetables. This species-specific response may be attributed to differential root architecture, rhizosphere microbiome compatibility, and nutrient uptake efficiency (Khan et al., 2019; Li et al., 2020).

The analysis of experimental conditions further demonstrated that soil type and cadmium concentration significantly influenced treatment efficacy. Treatments in loamy soils were associated with greater reductions in shoot cadmium content (mean reduction = 31.2%) compared to sandy soils (mean reduction = 19.8%), highlighting the role of soil physicochemical properties in modulating microbial and nutrient interactions. Moreover, moderate cadmium stress (5–10 mg/kg) showed more pronounced responses to microbial inoculation than high stress (>20 mg/kg), suggesting a threshold beyond which microbial interventions alone are insufficient to mitigate toxicity (Ghosh & Singh, 2020).

Overall, the results consistently indicate that both microbial inoculation and nutrient-mediated strategies substantially enhance plant growth, reduce cadmium accumulation in aerial tissues, and improve antioxidant defense under cadmium stress. These findings reinforce the concept of integrated microbial and nutrient management as an effective approach for alleviating heavy metal stress in crops (Singh et al., 2018; Zhao et al., 2021). While heterogeneity among studies exists, the robust statistical evidence supports the generalizability of these interventions across diverse plant species and experimental conditions.

4. Discussion

The present meta-analysis provides compelling evidence that microbial inoculation and nutrient management play a critical role in mitigating cadmium-induced stress in plants. Across the 42 studies analyzed, interventions involving arbuscular mycorrhizal fungi (AMF) and plant growth-promoting bacteria (PGPB) consistently improved plant growth parameters, particularly shoot and root biomass, while enhancing nutrient uptake. These results align with the fundamental understanding that microbial symbioses can buffer plants against heavy metal toxicity by facilitating metal sequestration, improving nutrient acquisition, and modulating physiological stress responses (Smith & Read, 2010; Glick, 2012). Enhancements in plant growth, photosynthetic efficiency, and antioxidant defense following microbial and combined microbial–nutrient interventions are presented in Table 3.

The forest plot analysis revealed that AMF inoculation generally produced higher effect sizes than PGPB treatments, suggesting that AMF may be more efficient in alleviating cadmium stress in aerial tissues. This observation is supported by studies demonstrating that AMF can enhance the accumulation of essential nutrients such as phosphorus, magnesium, and zinc while immobilizing cadmium in the rhizosphere, thereby reducing translocation to shoots (Jiang et al., 2015; Chen et al., 2016). PGPB, although exhibiting somewhat lower effect sizes, also significantly contributed to plant resilience by producing siderophores, phytohormones, and extracellular polysaccharides, which collectively reduce cadmium bioavailability and support root growth (Ma et al., 2016; Vessey, 2003). These mechanistic insights underscore the complementary roles of AMF and PGPB in improving plant performance under metal stress.

Nutrient management further amplified the beneficial effects of microbial inoculation. Several studies included in the meta-analysis demonstrated that the combined application of macro- and micronutrients with microbial inoculants led to synergistic outcomes, enhancing both biomass and antioxidant enzyme activity (Abbas et al., 2019; Li et al., 2017). Adequate nutrient availability supports the metabolic demands of plants under stress, enabling the synthesis of stress-responsive proteins and antioxidants such as superoxide dismutase and catalase, which mitigate oxidative damage induced by cadmium (Shahid et al., 2014; Gill & Tuteja, 2010). Enhancements in plant growth, photosynthetic efficiency, and antioxidant defense following microbial and combined microbial–nutrient interventions are presented in Table 3.  This integration of microbiota and nutrients creates a holistic defense mechanism, enhancing both growth and tolerance, a finding that resonates with the emerging paradigm of microbiome-assisted nutrient management in sustainable agriculture (Bhattacharyya et al., 2015; Wu et al., 2016).

Table 3. Effects of microbial and combined microbial–nutrient interventions on plant growth and antioxidant responses under cadmium stress
This table summarizes the effects of microbial inoculation alone and in combination with nutrient supplementation on plant growth, photosynthetic efficiency, and antioxidant enzyme activities under cadmium stress. It highlights synergistic benefits of integrated management strategies.

Despite the generally positive outcomes, the forest plot also indicated heterogeneity in treatment effects, with some studies reporting limited or non-significant improvements. Such variability likely reflects differences in plant species, soil characteristics, cadmium concentrations, and microbial strains (Khan et al., 2017; Rajkumar et al., 2012). For instance, leguminous plants often respond more favorably to microbial inoculation due to their inherent capacity for symbiotic nitrogen fixation, whereas non-legumes may require additional nutrient support to achieve comparable benefits (Begum et al., 2019). Similarly, soil pH, organic matter content, and texture influence microbial colonization and metal bioavailability, affecting the degree of stress alleviation (Wu et al., 2015). Understanding these context-specific variables is crucial for translating experimental findings into practical field applications.

The funnel plot (Figure 3) analysis indicated mild asymmetry, suggesting potential publication bias, particularly among small-sample studies reporting larger positive effects. However, sensitivity analyses confirmed that the overall pooled effect size remained robust, supporting the reliability of the meta-analytic conclusions (Egger et al., 1997; Sterne et al., 2001). This finding emphasizes the importance of critical appraisal and inclusion of unpublished or null-result studies to ensure balanced interpretation. Furthermore, the heterogeneity observed in the forest plot reinforces the need for standardized methodologies and reporting practices in studies examining microbiota-nutrient interactions under heavy metal stress (Ioannidis et al., 2001).

Mechanistically, the beneficial effects of microbial inoculation under cadmium stress are multi-faceted. AMF enhance metal sequestration in roots and promote compartmentalization within vacuoles, thereby protecting photosynthetic tissues (Chen et al., 2016). PGPB facilitate chelation and biosorption of cadmium through exopolysaccharides and siderophores, reducing its availability for uptake (Glick, 2012). Nutrients such as phosphorus, magnesium, and iron further support these processes by stabilizing cellular membranes, modulating antioxidant defense, and maintaining metabolic activity under stress (Shahid et al., 2014; Li et al., 2017). The meta-analysis confirms that interventions combining both microbial and nutrient approaches offer the most substantial gains, highlighting the importance of integrated strategies for managing cadmium toxicity.

These findings have practical implications for agriculture in cadmium-contaminated areas. The positive impact of microbial inoculation and nutrient supplementation on biomass and nutrient status suggests that these approaches can enhance crop yield and quality while reducing metal accumulation in edible tissues, thereby contributing to food safety (Rajkumar et al., 2012; Ma et al., 2016). Moreover, leveraging native microbial strains adapted to local soils may further optimize outcomes, emphasizing the need for site-specific recommendations rather than generalized interventions.

While the meta-analysis provides robust evidence, some limitations should be acknowledged. Variations in experimental design, cadmium concentrations, and microbial strains contribute to heterogeneity. Additionally, long-term field studies are limited, restricting the ability to assess sustained benefits under natural environmental conditions. Future research should focus on multi-location trials, optimization of inoculant formulations, and integration with sustainable nutrient management practices to maximize plant resilience and productivity.

The systematic review and meta-analysis demonstrate that microbial inoculation, particularly with AMF and PGPB, combined with appropriate nutrient supplementation, effectively mitigates cadmium-induced stress in plants. The synergistic interactions between microbes and nutrients enhance biomass, improve nutrient uptake, and reduce metal toxicity, offering a sustainable strategy for agriculture in contaminated soils. This integrative approach represents a promising avenue for improving plant health, ensuring food security, and promoting environmentally sustainable cultivation practices.

5. Limitations

Despite the growing body of research on the interplay between beneficial microbiota and nutrient-mediated alleviation of cadmium stress, several limitations constrain the generalizability and applicability of the findings. Most studies included in this systematic review and meta-analysis are conducted under controlled greenhouse or pot conditions, which do not fully replicate the complexity of field environments, including heterogeneous soils, fluctuating climatic factors, and multi-stress interactions. Additionally, variations in experimental designs, microbial strains, plant species, cadmium concentrations, and nutrient amendments create inconsistencies that challenge direct comparison across studies. Quantitative data for precise meta-analysis were limited, often relying on descriptive or relative measures rather than standardized statistical parameters, which may introduce bias and reduce the statistical power of pooled analyses. Moreover, long-term impacts of microbial inoculation and nutrient management on cadmium accumulation, plant health, and food safety remain underexplored. Interactions between microbial consortia and indigenous soil microbiomes are complex and context-dependent, further complicating the reproducibility and scalability of these studies. Finally, mechanistic understanding at molecular and omics levels is still emerging, limiting the ability to develop predictive models for nutrient–microbiome–cadmium interactions. Addressing these limitations will require large-scale field trials, standardized methodologies, and integrative approaches combining microbiology, plant physiology, and soil chemistry.

6. Conclusion

Beneficial microbiota, in conjunction with targeted nutrient management, provides a sustainable and effective approach to mitigating cadmium stress in crops. Harnessing these biological and nutritional interactions can enhance plant resilience, reduce cadmium uptake, and support safe, high-quality food production.

References