Tobacco is an economically important crop with a long worldwide cultivation history, and it is widely studied as a significant model plant that helps lay a foundation for agricultural biotechnological research (Sierro et al., 2014). Due to limited farmland areas and a lack of scientific cultivation methods, continuous tobacco cropping is often subject to continuous cropping obstacles even in the absence of major challenges such as pests, fertility, or climate change, and these obstacles cause poor growth of seedlings and a significant decrease in crop yield and quality (Chi et al., 2013; Niu et al., 2017). The causes of sustained decline in tobacco yield and quality are multifaceted, but autotoxicity is considered the most important influencing factor (Sun, 2010; Deng et al., 2017b).

Allelopathy broadly exists in the competition of plants and organisms for light, water, nutrients, and space, exerting an effect on the renewal of organisms, community succession, and seed germination in an ecosystem. As a particular form of allelopathy, autotoxicity affects plant growth in multiple ways, such as influencing cell membrane permeability, ion absorption, photosynthesis, and enzymatic activity, making it the major cause of continuous cropping obstacles for tobacco (Liu et al., 2010; Zhang et al., 2018; Zhang et al., 2021). Tobacco is fundamentally different from other crops in that it contains special bioactive substances, such as the aromatic components in secondary metabolites, and these causes tobacco to be more susceptible to allelopathic autotoxicity (Farooq et al., 2014; Deng et al., 2017b).

Soil microorganisms participate in many vital processes in the dynamics of the soil ecosystem, including the nutrient cycle, organic matter turnover, soil structure maintenance, and toxin degradation (Brussaard et al., 2007). Due to the rapid response of soil microorganisms to environmental changes and agricultural practices, they are considered a critical biological indicator for the efficacy of soil fertility and land management measures and are also known as the second genome of plants (Avidano et al., 2005; Wu et al., 2017). Changes in soil microflora are closely associated with continuous cropping obstacles as they significantly impact those vital processes in the soil ecosystem (Brussaard et al., 2007). The long-term continuous cropping of tobacco causes changes in the number of soil microorganisms, an imbalance in soil microecosystems, and a reduction in soil fertility, thus severely damaging the physicochemical properties of soil and the ecological environment. Under such influences, tobacco tends to exhibit retarded growth, dwarfed plants, reduced leaf area, and worsened diseases and pests, causing a decline in both yield and quality (Elsas et al., 2002; Nayyar et al., 2010). Therefore, researching the interactions between autotoxins and rhizosphere microorganisms lays a theoretical foundation for identifying the formation mechanisms of continuous cropping obstacles and the patterns of succession in the rhizosphere microorganism community.

Currently, tobacco production mainly relies on the application of pesticides and fertilizers, which not only causes cost increases and degrade tobacco quality but also pollutes farmland soil and the water environment, ultimately threatening human health. Research focusing on inducing plant immunity, improving cultivation measures, and utilizing microbiological methods to reduce continuous cropping obstacles during tobacco production can provide significant guidance and new approaches for seeking effective technologies that can sustainably improve the growth of continuously cropped tobacco.

Autotoxins can be generated by plant roots, stems, leaves, and fruits. These autotoxins contain a variety of carbon-based primary metabolites and more complex secondary compounds, such as root exudates, making them the largest inputs of chemical substances into the rhizosphere (Bertin et al., 2003; Hao et al., 2010; Huang et al., 2013). Autotoxins are thus considered the largest source of allelochemicals. These substances can be released into the environment through aboveground leaching, volatilization, root secretion, degradation and leaching, and some autotoxins, upon reaching a certain level of concentration, can cause autotoxicity in continuously cropped plants (Rial et al., 2014; Hisashi et al., 2017).

Autotoxicity poses a major threat to tobacco plants. On the one hand, it stimulates the growth of rhizospheric pathogenic bacteria while inhibiting that of beneficial microorganisms; on the other hand, it inhibits plant growth by affecting membrane systems, photosynthesis, and the enzymatic activity of plants, causing an allelopathic effect and inducing continuous cropping obstacles (Inderjit et al., 2006; Chen et al., 2022a). To clarify autotoxic and allelopathic effects, researchers have collected tobacco root exudates, and isolated, purified, and characterized autotoxins and evaluated their autotoxicity. Research indicates that autotoxins are mostly small molecules containing -OH, C=O, and S→O groups. They have simple structures and are difficult to degrade. These molecules contain oxygen atoms and easily excited double and triple bonds and are susceptible to release into the environment (Zhang et al., 2007b; Yu et al., 2015). Autotoxins are generally divided into water-soluble organic acids, linear alcohols, aliphatic aldehydes, and alkenes; simple phenols, benzoic acids, and their derivatives; simple unsaturated lactones, long-chain fatty acids, and polyacetylenes; naphthoquinone, anthraquinone, and quinone compounds; cinnamic acids and their derivatives; coumarins, tannins, terpenoids, and sterides; amino acids and polypeptides; alkaloids and cyanohydrins; sulfides and glucosinolates; and purines and nucleosides (Zhang et al., 2011b; Scavo et al., 2018; Blum, 2019). Many autotoxins associated with continuous cropping obstacles (p-hydroxybenzoic acid, homovanillic acid, vanillic acid, vanillin, cinnamic acid, ferulic acid, cumaric acid, benzoic acid, sesamin, momilactone B, etc.) have already been studied in different plant models (Kato-Noguchi et al., 2002; Nakano et al., 2006; Li et al., 2012; Ni et al., 2012; Yeasmin et al., 2014).

Using soils used for continuous tobacco cropping for 12 years, researchers comparatively examined the autotoxic potentials and differences in major chemical components between continuously cropped soils and controlled samples (Chen et al., 2011a). The study revealed that the rhizospheric soil of continuously cropped tobacco and its leach liquor had significant allelopathic autotoxicity against receiving plants such as lettuce and tobacco seedlings. GC-MS analysis showed that eight specific substances in the tobacco rhizospheric soil were associated with allelopathic autotoxicity, and vanillin showed relatively strong allelopathy; in contrast, only one alcohol with allelopathic autotoxicity was found in the control sample ( Table 1 ) (Chen et al., 2011a). The root exudates of tobacco contain various secondary compounds, and some are capable of accumulating around the rhizosphere and causing autotoxicity (Walker et al., 2003; Xie et al., 2007). β-Cembrenediol is considered as an essential autotoxin in the root metabolites of tobacco, which affects plant mitosis, enhances the generation of reactive oxygen and induces oxidative damage, increases the degree of lipid peroxidation of membranes, inhibits root and stem elongation, reduces the content of chlorophyll, and causes cell death (Ren et al., 2017). Substances such as din-butyl phthalate (DBP) and diisobutyl phthalate (DIBP) have been confirmed to be major autotoxins. At concentrations greater than 0.5 mmol, both substances have significant inhibitory effects on seed germination and seedling growth in tobacco and exhibit a synergistic effect for autotoxicity (Zhang et al., 2015; Deng et al., 2017a). Similarly, ferulic acid, benzoic acid, phthalates, and phenolic acids generated from the degradation of organic residues may be important autotoxins that cause the degradation of tobacco leaves (Yi et al., 2012). Furthermore, insect attractants such as muscalure resulting from the long-term continuous cropping of tobacco can attract pests and cause damage to tobacco growth (Miao et al., 2004; Chen et al., 2011a).

Autotoxicity is a special type of intraspecific competition, and it involves interactions between individuals using limited resources, which usually leads to density dependence or to self-thinning of plants. Autotoxin types vary by plant types (Tu et al., 2000), and factors such as the physicochemical properties of soil, abiotic stress, and microorganisms can cause intra- and interspecies differences in the types and concentrations of autotoxins. Different stimulation intensities of the various factors induce plant root systems to release different substances into the environment (Feng et al., 2010; Qin et al., 2021), including secretions, exudates, lysates, and mucilage. Specifically, substances that inhibit the growth of related plants are called autotoxins (Alías et al., 2006). Relative to plants in mature stages, those in the seed germination and seedling growth stages are considered more important for evaluating autotoxicity processes (Lara-Núñez et al., 2010; Margot et al., 2012), as plants are more susceptible to the effect of autotoxins during these stages (Callaway and Aschehoug, 2000; Callaway and Ridenour, 2004; Weir et al., 2004). Many autotoxins have been found to affect seed germination, seedling growth, photosynthesis, nutrient absorption, cell division, cytoskeleton formation, generation of reactive oxygen species, and the expression of functional genes ( Figure 1 )(Inderjit and Duke, 2003; Blum and Gerig, 2005; Zhang et al., 2010a; Soltys et al., 2011).

Autotoxins affect tobacco growth conditions in fields and its agronomic traits, causing a reduction in growth parameters such as plant height and leaf area coefficients during the vigorous growing and budding stages and to poor root growth and development (You et al., 2015a). Long-term continuous cropping of tobacco leads to an accumulation of large amounts of autotoxins, causing a decline in tobacco biomass, yield, and quality; a decrease in tobacco photosynthesis, transpiration rate, and potassium and sugar contents; an increase in nicotine content; and a degradation in aroma quality (Jing and Matsui, 1997; Yu et al., 2000; Chen et al., 2010; Zhang et al., 2011a; Chen et al., 2022b). A study indicated that as autotoxins accumulate, the weights of tobacco stems, roots, and leaves exhibit significant declining trends (Zhang et al., 2007a). Increasing the time of continuous tobacco cropping leads to a significant reduction in the total sugar level, reducing sugar and potassium levels, and to a downward trend of its major economic trait indicators, leading to adverse effects on smoking quality (Fu et al., 2018). A number of studies have shown that 1 year of continuous cropping causes a reduction in the total nitrogen content of tobacco, 2 years of continuous cropping causes an upward trend in nicotine content, and 3(+) years of continuous cropping significantly reduces the percentage of medium-grade tobacco and its qualities, as well as its Schmuck value, K/Cl ratio, and sugar-to-nicotine ratio (Jin et al., 2002; Jin et al., 2004; Zhao et al., 2008). The effect of autotoxins on tobacco varies based on their concentrations. Among the root metabolites of tobacco, benzoic acid, cinnamic acid, and p-hydroxybenzoic acid significantly inhibit the growth of tobacco radicles at concentrations higher than 100 μg/ml, whereas ferulic acid significantly inhibits tobacco seed germination, seedling growth, and radicle elongation (Zhang et al., 2013).

The types and numbers of root exudates, which serve as the medium for interactions between plants and rhizosphere microorganisms, are important factors influencing the number, activity, and diversity of soil microorganisms (Bais et al., 2006). The carbohydrates, organic acids, amino acids, ectoenzymes, and autotoxins contained in root exudates not only provide energy, signaling molecules, and growth substrates for the growth and reproduction of rhizosphere microorganisms but also exert selective and facilitating effects on particular microbial populations (Badri and Vivanco, 2009; Gabriele and Kornelia, 2010; Huang et al., 2014; Rohrbacher and St-Arnaud, 2016). By regulating nutrient absorption, as well as the growth and development of plants and soil properties, autotoxins indirectly control the diversity of rhizosphere microorganisms (Broeckling et al., 2008). Such changes stimulate root systems to accumulate more autotoxins, simplifying the microbial population structure of the rhizospheric soil, reducing the types of dominant soil microorganisms populations, and making them mainly concentrated on Acidobacteria (Liu et al., 2016; Li, 2017; Chen et al., 2018b). In contrast, the dominant soil microorganism populations in tobacco rotation-cropped fields are primarily Acidobacteria, γ-proteobacteria, and α-proteobacteria, showing a high level of microbial diversity (Duan et al., 2012). The longer continuous cropping is practiced, the worse the tobacco diseases (Chen et al., 2022b). Dysfunctions or variations in the flora of soil microorganisms associated with tobacco plants cause a reduction in the number, abundance, and diversity of probiotic bacterial populations in soil (ammonificator and nitrifier), a decrease in the number of bacteria, and an increase in the number of fungi and actinomycetes (Wang et al., 2008), inducing a shift in the continuously cropped soil from highly fertile “bacterial” soil to less fertile “fungal” soil (Niu et al., 2017). This increases the number of pathogens and disease morbidity rates of tobacco, causing continuous cropping obstacles ( Figure 1 ) (Duan et al., 2012). Black shank disease, tobacco mosaic, root-knot nematode, black root rot, tobacco black death disease, and tobacco bacterial wilt are all positively correlated with the accumulation of autotoxins (Zhang et al., 2011b). Autotoxins such as gallic acid, p-hydroxybenzoic acid, and ortho-hydroxybenzoic acid also stimulate the germination of spores of bacteria causing Fusarium wilt and Verticillium wilt (Zhang et al., 2012b). In addition, the activities of urease, acidic phosphatase, and saccharase in rhizospheric soil also gradually decrease, compared with a significant increase in the activity of catalase (Zhang et al., 2007c).

The accumulation of beneficial rhizospheric substances may be an important factor in reducing autotoxin-induced damage. As important components that sustain the productivity of soil, rhizosphere microorganisms affect the structure, function, and processes of soil ecosystems (Chen et al., 2022b), inhibit soil-borne diseases in host plants, increase plant nutrient absorption and stress resistance, and decompose autotoxins, thereby facilitating plant growth. Research shows that inoculating plants with Pseudomonas putida helps decompose 99.47% of p-hydroxybenzoic acid in Hoagland’s nutrient solution within 72 h (Chen et al., 2015). Pseudomonas putida, Pseudomonas nitroreducens, and Rhodotorula glutinis can effectively decompose ferulic acid, p-hydroxybenzoic acid, and p-hydroxybenzaldehyde (Zhang et al., 2010b). Micrococcus lylae, Phyllobacterium myrsinacearum, and Leminorella grimontii can decompose oleic acid, hexadecanoic acid, and phthalic acid, respectively, and multistrain bacterial assemblages can achieve a degradation rate of 66.7% for allelochemicals (Zhao et al., 2016). Small molecular volatile compounds generated by microbial metabolism spread quickly in the atmosphere and soil (Hung et al., 2015). For example, signaling factors such as N-acyl-L-homoserine lactones significantly upregulate the expression of genes associated with vegetative storage proteins, γ-glutamyl hydrolase, and Rubisco large proteins, thus increasing the systemic resistance in plants (Timmusk et al., 2014; Vaishnav et al., 2015). Adipic acid, butyric acid, 2-undecanone, 7-hexanol, 3-methyl-butanol, and dimethyl disulfide produced by strains such as Alcaligenes faecalis and Paraburkholderia phytofirmans have also been confirmed to facilitate plant growth and induce stress tolerance (Bhattacharyya and Jha, 2012; Ledger et al., 2016).

The objective of autotoxicity management is to reduce the production of autotoxins and to increase the elimination of produced autotoxins. To this end, we propose combined management strategies ( Figure 2 ).

Autotoxicity is a key factor that limits yield and quality improvements in tobacco, and it is a pressing agricultural problem to be addressed. In this study, the types and composition of tobacco autotoxins present under continuous cropping systems were summarized, and a model for the toxicity of autotoxins toward tobacco and soil microorganisms was proposed. This study also proposes a combination of management strategies for remediating tobacco autotoxicity.

Presently, studies focusing on the action mechanism of autotoxins have mostly been limited to phenomenological descriptions. To further explore tobacco–soil–microorganism interactions and develop more practical preventive measures against autotoxins, accelerate the promotion of autotoxin prevention technology, and reduce damage caused by tobacco autotoxicity, further studies are recommended from the following perspectives:

YC: conceptualization, visualization, writing—original draft preparation, writing—review and editing. LY: conceptualization, validation, funding acquisition, writing—original draft preparation. LZ: investigation, writing—review and editing. JL: investigation, writing—review and editing. YZ: visualization, writing—review and editing. WY: investigation, writing—review and editing. LD: investigation, writing—review and editing. QG: investigation, writing—review and editing. QM: supervision, writing—review and editing. XL: supervision, writing—review and editing. WZ: conceptualization, validation, writing—review and editing. XD: conceptualization, validation, writing—review and editing. HX: conceptualization, validation, funding acquisition, writing—review and editing. All authors contributed to the article and approved the submitted version.