A Review on Gut Remediation of Selected Environmental Contaminants: Possible Roles of Probiotics and Gut Microbiota

Various environmental contaminants including heavy metals, pesticides and antibiotics can contaminate food and water, leading to adverse effects on human health, such as inflammation, oxidative stress and intestinal disorder. Therefore, remediation of the toxicity of foodborne contaminants in human has become a primary concern. Some probiotic bacteria, mainly Lactobacilli, have received a great attention due to their ability to reduce the toxicity of several contaminants. For instance, Lactobacilli can reduce the accumulation and toxicity of selective heavy metals and pesticides in animal tissues by inhibiting intestinal absorption of contaminants and enhancing intestinal barrier function. Probiotics have also shown to decrease the risk of antibiotic-associated diarrhea possibly via competing and producing antagonistic compounds against pathogenic bacteria. Furthermore, probiotics can improve immune function by enhancing the gut microbiota mediated anti-inflammation. Thus, these probiotic bacteria are promising candidates for protecting body against foodborne contaminants-induced toxicity. Study on the mechanism of these beneficial bacterial strains during remediation processes and particularly their interaction with host gut microbiota is an active field of research. This review summarizes the current understanding of the remediation mechanisms of some probiotics and the combined effects of probiotics and gut microbiota on remediation of foodborne contaminants in vivo.


Introduction
The anthropogenic activities, rapid industrialization and urbanization have resulted in generation of hazardous toxic pollutants and consequent contamination of soil and water resources. For example, antibiotics (ABs) from medical waste, livestock manure and aquatic breeding have resulted in surface water contamination [1]. In addition, the large area of soil is contaminated by heavy metals (HMs) depositions and pesticides spraying [2]. It is reported that about 2.5 million hectares of soil area in Europe alone is a victim of pollution [3]. In China, mining has resulted in severe HMs contamination of 2.88 × 10 6 ha of land, with an additional mean area of 46,700 ha polluted annually [4]. HMs and pesticides can accumulate in agricultural products grown in the contaminated soil [5,6]. Hence, these environmental contaminants are readily transmitted into human body through water and diet, exerting

Pesticides
Pesticides are widely applied in agriculture to resist insects, weeds, and plant pathogens to promote plant growth. The crops are exposed to pesticides, which can readily get into human GIT through daily diet. Low levels of pesticides exposure can give rise to long-lasting adverse effects on skin, endocrine, and especially nervous system by inducing generation of free radicals that might cause lipid peroxidation, DNA damage, cell death and possible carcinogenic effects [52][53][54].
Many researchers have demonstrated the essential role of GM in the metabolism of pesticides in host. Some pesticides are known to be metabolized by the enzymes produced by GM. Organophosphate insecticide chlorpyrifos get metabolized into a more toxic molecule 3,5,6-trichloro-2-pyridinol via biotransformation by GM, resulting in biologically relevant and toxic consequences on host health. Whereas certain bacterial species, e.g. Pseudomonas spp. (ATCC700113), L. lactis, E. coli and L. fermentum present in GIT, are capable of utilizing 3,5,6-trichloro-2-pyridinol as their sole carbon and energy source [55][56][57]. In turn, the composition and function of GM are profoundly affected by long-term exposure to pesticides, correlated with various metabolic and immune diseases [28].
Organophosphorus (OP) pesticide has been extensively applied since 1950s. Chlorpyrifos is a typical OP insecticide that can result in altered host metabolism, increased bacterial translocation, and alterations in GM compositions. For instance, chronic chlorpyrifos exposure in rats increased the abundance of opportunistic pathogens, and unfavorable metabolic-related strains, resulting in obese and diabetic phenotypes [58]. In addition, chlorpyrifos exposure affected the proliferation of subpopulations of some strains (Enterococcus spp., Bacteroides spp.) and increased bacterial translocation in spleen and liver of rats [59,60]. In the simulator of the human intestinal microbial ecosystem(SHIME) model, chlorpyrifos also had a great impact on the population of culturable bacteria, leading to an increase in Enterobacteria, Bacteroides spp., Clostridia count and decrease in Bifidobacterial count [60,61]. Similar experiments conducted in mice showed that the relative abundance of some key microbes was significantly altered under chlorpyrifos stress, with altered urine metabolites related to the metabolism of amino acids and energy, SCFAs, phenyl derivatives and bile acids [62]. Different bile acids can bind to different receptors and promote the absorption of dietary fats, regulate lipid and glucose metabolism, and shape the GM [63,64]. GM can transform bile acids and altered GM would influence the pool of bile acids and the host's energy metabolism.
Malathion, diazinon and glyphosate are another three representatives of OP pesticide. In malathion-treated mice, gut microbiome development and quorum sensing were perturbed, with an increase in the relative abundance of bacterial genes associated to quorum sensing-related behaviors such as motility and pathogenicity [65]. Sex-specific impact on gut microbiome by diazinon was examined in a mouse model. Specifically, several bacterial genera, including Bacteroidaceae_Bacteroides, Burkholderiales_Other, Clostridiaceae_Other, and Erysipelotrichaceae_ Coprobacillus, were only observed in male mice, while Lachnospiraceae_Butyrivibrio Lachnospiraceae_Shuttleworthia, and Staphylococcaceae_ Staphylococcus were completely inhibited in males after diazinon exposure [66]. The effect of glyphosate on poultry microbiota was evidenced by the elevated resistance of pathogenic bacteria including Salmonella entritidis, Salmonella gallinarum, Salmonella typhimurium, Clostridium perfringens and Clostridium botulinum, and increased susceptibility of most of the beneficial bacteria such as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lactobacillus spp. [67].
Organochloric pesticide (OCP), another type of common pesticide, interferes with intestinal flora, lipid metabolism, and tissue and body weight in animals. In mice, OCP induced increased abundance of Firmicutes and Proteobacteria, and decreased abundance of Bacteroidetes, Verrucomicrobia, and Actinobacteria. Meantime, the expression of genes involved in bile acid reabsorption by the terminal ileum was down-regulated, and compensatory expression of genes in synthesis of bile acids was up-regulated in the liver [68]. When permethrin was administered through diet in rat, it caused reduction in abundance of Bacteroides-Prevotella-Porphyromonas species and increase in the abundance of Enterobacteriaceae and Lactobacillus in fecal microbiota; altered SCFAs levels were registered over a 4-month period [69]. Pentachlorophenol exposure in gold fish led to an increased in the Bacteroidetes abundance and a decrease in the ratio of Firmicutes to Bacteroidetes in the gut, which played crucial roles in the reduction of body weight. Bacteroides genus within the Bacteroidetes phylum was significantly correlated with pentachlorophenol exposure dosage and duration [70].
Imidazole is widely used to inhibit fungus in agriculture. Recent studies revealed that GM dysbiosis induced by imidazole exposure is often associated with hepatic metabolism disorder and hepatic toxicity. When imazalil was orally given in zebrafish and mice, the abundance of Bacteroidetes was decreased, and Firmicutes increased in the gut at phylum level. In mice at the genus level, the abundance of Lactobacillus and Bifidobacterium decreased while those of Deltaproteobacteria and Desulfovibrio increased in response to imazalil exposure. In addition, the transcription of genes such as Aco, Cpt1, Acc1, Srebp1a and Fas, related to glycolysis and lipid metabolism was significantly decreased in the mouse liver [71,72]. In the mice that were exposed to carbendazim, the amounts of Bacteroidetes in the feces, and richness and diversity of GM in the cecum decreased significantly after the 5-day exposure. Analysis of operational taxonomic units (OTU) indicated that a total of 361 out of 3271 identified OTUs were significantly changed [31].

ABs
Abs are widely used in stockbreeding, veterinary and human medicines [73,74]. Part of the ingested ABs by humans and animals can enter the environment through feces or urine [75]. Large quantity of ABs was detected in the ecosystem [76,77]. Hence, humans are readily exposed to antibiotic contamination passively in addition to medical route. The side effects of ABs range from relative mild ones, such as allergy, asthma, and diarrhea to severe ones, e.g., death [78].
ABs administration has been correlated with changes in the population structure of microbiome, which might be linked to a multitude of diseases. In particular, AAD and Clostridium difficile infections can be common following ABs treatment [79,80]. It has been previously shown that the microbial diversity was significantly reduced after treatment with ampicillin, streptomycin and clindamycin in the cecal and large intestine contents of mice. The Bacteroidetes population was drastically reduced, which never fully recovered following cessation of treatment, and the outgrowth of two dominant genus, Stenotrophomonas and Xanthamonas [81]. The predominant genus Stenotrophomonas is noteworthy since this highly antibiotic resistant bacterium is also a potential emerging opportunistic pathogen [82]. Treatment with clindamycin and ampicillin made the patients susceptible to Clostridium difficile infection and decreased Clostridium scindens count, which is a secondary modulator of bile acid metabolism [83]. A number of recent studies revealed that the abundance of Proteobacteria phylum in microbiota was significantly increased as a consequence of antibiotic administration [84][85][86]. Proteobacteria encompass a wide variety of pathogens, such as Escherichia, Vibrio, Salmonella, Helicobacter, Yersinia, Legionellales and others. E. coli is responsible for a vast majority of Escherichia-related pathogenesis, and other members of this genus have also been implicated in human diseases [87,88]. Salmonella species are known intracellular pathogens and certain serotypes are responsible for illness [89]. Altogether these findings suggest that altered structure of intestinal microbiota is related to the pathogenesis of diseases.
ABs can affect the colonization resistance of host. Treatment with cefoperazone [90], tigecycline [79], clindamycin [80], or clindamycin in combination with a five-antibiotic cocktail in C57BL/6 mice had decreased the colonization resistance, as a result of a decrease in Lachnospiraceae and Barnesiella and an increase in Lactobacillaceae and Enterobacteriaceae. These results were largely consistent with human studies [91,92].
Effect of ABs on GM can be persistent. Fouhy et al. (2012) [84] evaluated the short-term recovery of the GM following parenteral ampicillin and gentamicin treatment for infant within 48 hours of birth. It was shown that the abundance of Proteobacteria remained significantly higher and the number of different Bifidobacterium species was reduced in the infants after 8 weeks of treatment with ABs. It is, thus, obvious that the use of certain ABs in early life can significantly affect the evolution of the infant GM. Another study investigated the short and long-term effects of macrolides on 2-7 year old children (N = 142), and found depletion of Actinobacteria, increased abundance of Bacteroidetes and Proteobacteria and increased macrolide resistance, which can persist for over 6 months. Additionally, it was mentioned that the use of macrolides in early life increased the risk of asthma and weight gain [85]. A study in mice reported that Bacteroidetes was drastically reduced following treatment with the antibiotic mixture of ampicillin, streptomycin, and clindamycin and never fully recovered after cessation of ABs treatment [81].
The literature regarding the role of altered GM in the development of ABs-related side effects, however, is scarce. The current understanding is that oral intake of ABs lead to disturbance of composition and more importantly the metabolism of GM, which might correlate with disrupted physiology of the host. Study in mice treated with combinative ABs of penicillin, vancomycin and chlortetracycline revealed significant alterations of microbial structure, and altered regulation of hepatic metabolism of lipids and cholesterol, as well as increase of the copies of key genes involved in the metabolism of SCFAs synthesis in fecal and cecal samples [93]. Metagenomic analysis in mice receiving early-life therapeutic-dose pulsed tylosin showed that tylosin intervention decreased the modules involved in glycolysis, gluconeogenesis and tRNA biosynthesis and increased the modules involved in citric acid cycle and nucleoside and amino acid biosynthesis [94]. A study in piglets treated with a mixture of ampicillin, gentamicin and metronidazole also indicated that altered GM was associated with increased metabolism of aromatic amino acids and decreased expression of neurotransmitter in hypothalamus [95]. ↑: Increase of relative abundance of the species or the severity of the outcomes; ↓: Decrease of relative abundance of the species or the severity of the outcomes.

Probiotics as a Potential Tool in Contaminants Remediation
Increasing evidence demonstrated that oral supplementation of probiotics is one of the effective strategies for protection against foodborne contaminants-induced toxicity. In general, probiotics applied in toxicant remediation are selected based upon their safety and viability during passage through the GIT [97] and importantly their capacity of contaminants adsorption [98]. The probiotic effects on the hosts are usually assessed by monitoring the individual growth, measuring the amount of pollutant and related biomarkers in tissues, and analyzing the compositional and functional changes of stool microbiota using 16S rRNA sequencing in murine and other models. Nonetheless, the interaction between probiotics and the GM is still poorly understood.

Role of Probiotics in HMs Remediation In Vivo
The protective effects of probiotics against HMs toxicity have been extensively studied. Supplementation of single probiotic or a combination of probiotics in mammalians has shown positive results in alleviating the toxicity of HMs including Cd, Hg, Cr, As and Pb ( Table 2).
Probiotics utilized to reduce the toxicity of HMs are generally Lactobacilli, as they have excellent binding capacity for HMs, evidently lowering the availability of HMs for the host [99]. It has also been speculated that living probiotic strain L. plantarum CCFM8610 might competitively inhibit the intestinal absorption of Cd by increasing the dissolution and uptake of divalent essential elements like Ca, Mg, and Fe [18]. Probiotic strains can also promote gastrointestinal peristalsis, hence the excretion of HMs in feces is facilitated [18]. Furthermore, probiotic strains can limit the entrance of HMs by enhancing intestinal barrier function and regulating tight junction of epithelium of small intestine. Administration of L. plantarum CCFM8610 reversed all of the reductions of mRNA expression of tight-junction proteins (ZO-1, ZO-2, occludin, and claudin-1) caused by Cd exposure, decreased intestinal permeability and reduced Cd leakage into systemic circulation [50]. Preventing systemic absorption of HMs by probiotics thus leads to alleviation of oxidative stress in various tissues and consequent mitigation of tissue damages as reported [100][101][102]. For example, co-treatment of L. plantarum CCFM8610 and Cd cause a decreased production of metallothionein and downregulation expression of genes in the mitogen-activated protein kinases (MAPK) pathways in the liver [19]. Metallothionein has a high affinity for divalent cations [103] and the MAPK pathway is associated with reactive oxygen species production [19]. More recently, evidences have suggested that probiotics play a role in restoring the altered composition and function of GM induced by HMs. L. reuteri DSM17938 intervention contributed to restoring intestinal homeostasis in patient with low-Ni diets and the increase of lactic acid bacteria (LAB) biodiversity [104]. In the case of reducing Cr (VI) toxicity in mice, the crucial role of probiotic strain L. plantarum TW1-1 in maintaining GM homeostasis and enhancing Cr (VI)-reduction ability of intestinal bacteria was underscored [29]. The proposed protective mechanisms of probiotics on HMs remediation are shown in Figure 1.
To date, almost all studies on the efficacy of probiotics were carried out in animals, the only case reported in human was that of L. rhamnosus GR-1 (LGR-1)-supplemented yogurt which protected against the absorption of As and Hg in pregnant women and children [105]. Moreover, the effect of HM bioremediation by probiotics is strain-dependent and specific. Although the strain LGR-1 was effective in reducing Hg and As absorption, it could not significantly reduce the blood levels of Pb and Cd in populations, indicating the need for specific probiotics or cocktails of probiotics for protection against different types of HMs.  To date, almost all studies on the efficacy of probiotics were carried out in animals, the only case reported in human was that of L. rhamnosus GR-1 (LGR-1)-supplemented yogurt which protected against the absorption of As and Hg in pregnant women and children [105]. Moreover, the effect of HM bioremediation by probiotics is strain-dependent and specific. Although the strain LGR-1 was effective in reducing Hg and As absorption, it could not significantly reduce the blood levels of Pb and Cd in populations, indicating the need for specific probiotics or cocktails of probiotics for protection against different types of HMs.

Probiotics' Role in Pesticides Remediation In Vivo
Expensive drugs have been developed and long-time therapies have been employed to fight against damages caused by pesticides [106]. More economic alternatives are hence needed to reduce the adverse effects of pesticides. Mounting evidences have highlighted probiotics in mitigating the adverse effects of pesticides (Table 2), and their protective mechanisms are summarized as below. First, Lactobacilli protect against pesticides-induced oxidative stress and downstream cellular damage. A few researches have shown that supplementation with L. plantarum BJ0021 can decrease oxidative stress and MDA concentration in liver and kidney induced by endosulfan [107]. Another study showed L. casei ATCC334 could decrease DNA damage in rats exposed to a carcinogen 1, 2-dimethylhydrazine [54]. Second, probiotics maintain the integrity of intestinal barrier and reduce the absorption of pesticides [108]. It was found that L. plantarum MB452 enhanced the expression of tight junction proteins occludin, ZO-1, ZO-2, and cingulin in the Caco-2 intestinal cell-line [109]. Probiotics L. rhamnosus strain GG (LGG) and LGR-1 reduced the absorption of parathion or CP in a Caco-2 Transwell model [21]. Third, recent studies found that a few probiotics, mainly Lactobacillus from dairy products and wheat, were capable of degrading OCP enzymatically with phosphohydrolase [98,110]. Fourth, Lactobacilli stimulate host's own immunity and detoxification mechanisms to resist pesticides and pathogen invasion. In the study using pattern insects, L. casei

Probiotics' Role in Pesticides Remediation In Vivo
Expensive drugs have been developed and long-time therapies have been employed to fight against damages caused by pesticides [106]. More economic alternatives are hence needed to reduce the adverse effects of pesticides. Mounting evidences have highlighted probiotics in mitigating the adverse effects of pesticides (Table 2), and their protective mechanisms are summarized as below. First, Lactobacilli protect against pesticides-induced oxidative stress and downstream cellular damage. A few researches have shown that supplementation with L. plantarum BJ0021 can decrease oxidative stress and MDA concentration in liver and kidney induced by endosulfan [107]. Another study showed L. casei ATCC334 could decrease DNA damage in rats exposed to a carcinogen 1, 2-dimethylhydrazine [54]. Second, probiotics maintain the integrity of intestinal barrier and reduce the absorption of pesticides [108]. It was found that L. plantarum MB452 enhanced the expression of tight junction proteins occludin, ZO-1, ZO-2, and cingulin in the Caco-2 intestinal cell-line [109]. Probiotics L. rhamnosus strain GG (LGG) and LGR-1 reduced the absorption of parathion or CP in a Caco-2 Transwell model [21]. Third, recent studies found that a few probiotics, mainly Lactobacillus from dairy products and wheat, were capable of degrading OCP enzymatically with phosphohydrolase [98,110]. Fourth, Lactobacilli stimulate host's own immunity and detoxification mechanisms to resist pesticides and pathogen invasion. In the study using pattern insects, L. casei was found stimulating phase-II detoxification system and rescued malathion-induced physiological impairments in Caenorhabditis elegans [20]. Probiotic L. plantarum ATCC14917 has shown to stimulate immunity, and lower the pathogenic microorganism (Serratia marcescens) infections in fruit flies exposed to imidacloprid [111].

Probiotic Intervention in AAD Patients and Animal Models
There are a significant number of studies demonstrating the benefits of probiotics in reducing the occurrence of AAD, allergy, lactose intolerance, reduction of cholesterol etc. [112,113]. Patients receiving ABs for treatments are prone to suffer from gastrointestinal disturbances result from damage of the GI mucosal cells and disruption of the gut ecological balance. Probiotics replenish the natural GIT with nonpathogenic bacteria, and are considered as living drugs that help with ABs-associated diseases, without affecting the efficacy of ABs.
There are many favorable outcomes of probiotics in reducing the risk of AAD in adults and children based on extensive meta-analyses, and only a few studies using probiotics in patients undergoing antibiotic failed to acquire significant effect [114,115]. In a trial study with 246 children, co-treatment of Saccharomyces boulardii and ABs has been reported to lower the risk of diarrhea from 20.9% to 8.8% [116]. The updated results of meta-analysis, based on 10 RCTs, also showed that S. boulardii effectively prevented AAD in patients, with decrease of risk from 17.4% to 8.2% in adults [117]. The efficacy of LGG for preventing AAD in children and adults has also been evaluated. Treatment with LGG reduced the risk of AAD in patients receiving ABs from 22.4% to 12.3% [118]. The hospital patients who were administered with bio-yogurt containing a combined dose of L. acidophilus, L. delbrueckii, subspecies bulgaricus, and S. thermophiles showed reduced risk from 24% to 12% of AAD [119]. Furthermore, the effects of single and combinative probiotics on preventing AAD were compared. A meta-analysis in 2006 has reported that most of the RCTs used combinations of Lactobacillus species which were effective against diarrhea and the relative risk of AAD is 0.43, but there is no high-quality evidence for a single probiotic strain except for S. boulardii [120].
The efficacy of probiotic strains in reducing the risks of AAD in humans have been evidenced, however, the underlying mechanism of these probiotic strains is less well understood. By reviewing recent literatures (Table 2), probiotics have been proposed to be effective in alleviating ABs-associated diseases through multiple routes ( Figure 2): (1) mediating the structure of gut microbial community [81,121,122] by promoting beneficial bacteria and suppressing opportunistic pathogens. A cocktail of L. rhamnosus A 191, L. acidophilus, B. breve and B. longum significantly caused suppression of gut opportunistic pathogens Enterobacteriaceae and promotion of Firmicutes following ABs treatment in mice [81]. In another study, it was confirmed that probiotic cocktail of four Lactobacillus species JUP-Y4 treatment decreased the levels of Desulfovibrionales, and promoted the levels of Akkermansis [122]. High abundance of Desulfovibrionales were related with Crohn's disease [123] and human infections [124,125], and Akkermansis are biomarkers of intestinal health [126] and inversely linked with the severity of Crohn's disease and ulcerative colitis [127]. Two probiotics Phaeobacter inhibens S4Sm and Bacillus pumilus RI06-95Sm in black molly, have been shown to colonize in intestine and reverse mortality caused by streptomycin by inhibiting Vibrio anguillarum [121], which are known opportunistic pathogens in fish [128] and are thought to be "r-strategists" capable of rapid growth and virulence in disturbed microbial communities [129,130]. (2) Improving immune function of host by enhancing anti-inflammation [131][132][133][134]. Shi et al. (2017) used two Lactobacillus cocktails (LacA and LacB, each contains four strains) to restore the cefixime-induced GM disturbance in mice, and alleviate intestinal inflammation possibly due to beneficial SCFAs production [134]. A probiotic compound of Streptococcus thermophiles, B. breve, B. longum, etc., also reportedly restored the expression of anti-inflammatory cytokine IL-10 completely without affecting pro-inflammatory mediators in mice following broad-spectrum antibiotic treatment. At the meantime, adaptive immunity was also restored, with increase of CD4+, CD8+, and B220+ cell numbers in the intestinal lamina propria [132]. Separate studies demonstrated that S. boulardii can up-regulate antitoxin A secretory IgA expression in animal models of AAD [135,136]. (3) Enhancing intestinal barrier function. A probiotic cocktail JUP-Y4 modulated ampicillin induced gut barrier dysfunction and GM disturbance in mice. Increased expression of intestinal epithelial tight-junction proteins, and reduced inflammatory cytokines in the ileum and the colon following JUP-Y4 use contributed to caecum tumefaction attenuation and a decrease in gut permeability [122]. Probiotics have also been shown to increase epithelium mucins production, which is a critical element of the epithelium barrier [137,138]. Probiotics also assist in producing antagonistic activity like bacteriocins against pathogenic bacteria, and inhibiting bacterial translocation by competing for receptors or adhesion to endothelial cells [139][140][141]. JUP-Y4 use contributed to caecum tumefaction attenuation and a decrease in gut permeability [122]. Probiotics have also been shown to increase epithelium mucins production, which is a critical element of the epithelium barrier [137,138]. Probiotics also assist in producing antagonistic activity like bacteriocins against pathogenic bacteria, and inhibiting bacterial translocation by competing for receptors or adhesion to endothelial cells [139][140][141].

Conclusions and Future Perspectives
The foodborne contaminants, such as HMs, pesticides and ABs, cause harmful effects on animal and human health. GM is a major player in the remediation of these contaminants. Both contaminants-induced toxicity and impaired structure and metabolic activity of GM have significant impacts on target organs, causing tissue damage and other disease. Dietary supplementation with probiotics appears to be a promising adjunct intervention for effectively reducing the damage caused by foodborne contaminants and re-balancing the GM of humans and animals under a constant threat of pollutants.
The understanding of host-GM interactions must be further developed using a series of techniques such as metagenomics, metatranscriptomics and metabonomics, to provide meaningful insights into the mechanisms of GM, and to clarify the causal relationship between GM and GM-associated symptoms. Additionally, this work needs to be extended to human studies, as majority of research on contaminants remediation using probiotics comes from animal models, rather than humans. Meanwhile, almost all of current studies on the GM and contaminants solely rely on stool microbiota, which is part of the GM and may yield limited conclusions [146]. Hence gut mucosal sampling should also be considered in future studies. Furthermore, the colonization of probiotics in human may vary from person to person, depending on factors such as the composition of individual community, the composition of the colonizers, and intrinsic host factor [147]. Thus, in future applications with probiotics in human, personalized probiotic regimen based on the consumer at different contexts must be considered.
Author Contributions: P.L. and X.L. reviewed the manuscript; P.F. and Z.Y. wrote the manuscript; A.K. and A.K.V. prepared the figures and tables.