Research advances in detection of food adulteration and application of MALDI-TOF MS: A review.

Food adulteration and illegal supplementations have always been one of the major problems in the world. The threat of food adulteration to the health of consumers cannot be ignored. Food of questionable origin causes economic losses to consumers, but the potential health risks cannot be ignored. However, the traditional detection methods are time-consuming and complex. This review mainly discusses the types of adulteration and technologies used to detect adulteration. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is also emphasized in the detection of adulteration and authenticity of origin analysis of various types of food (milk, meat, edible oil, etc.), and the future application direction and feasibility of this technology are analyzed. On this basis, MALDI-TOF MS was compared with other detection methods, highlighting the advantages of this technology in the detection of food adulteration. The future development prospect and direction of this technology are also emphasized.

Mechanistic insights into the changes of biological activity and physicochemical characteristics in Lacticaseibacillus paracasei fortified milk powder during storage.

To clarify the change mechanism of biological activity and physicochemical characteristics in Lacticaseibacillus paracasei JY025 fortified milk powder (LFMP) during storage, morphological observation, JY025 survival, storage stability, and metabolomics of LFMP were determined during the storage period in this study. The results showed that the LFMP had a higher survival rate of JY025 compared with the bacterial powder of JY025 (LBP) during storage, which suggested that milk powder matrix could reduce strain JY025 mortality under prolonged storage in the LFMP samples. The fortification of strain JY025 also affected the stability of milk powder during the storage period. There was lower water activity and higher glass transition temperature in LFMP samples compared with blank control milk powder (BCMP) during storage. Moreover, the metabolomics results of LFMP indicated that vitamin degradation, Maillard reaction, lipid oxidation, tricarboxylic acid cycle, and lactobacilli metabolism are interrelated and influence each other to create complicated metabolism networks.

Self-assembled bifunctional nanoflower-enabled CRISPR/Cas biosensing platform for dual-readout detection of Salmonella enterica.

Sensitive detection and point-of-care test of bacterial pathogens is of great significance in safeguarding the public health worldwide. Inspired by the characteristics of horseradish peroxidase (HRP), we synthesized a hybrid nanoflower with peroxidase-like activity via a three-component self-assembled strategy. Interestingly, the prepared nanozyme not only could act as an alternative to HRP for colorimetric biosensing, but also function as a unique signal probe that could be recognized by a pregnancy test strip. By combining the bifunctional properties of hybrid nanoflower, isothermal amplification of LAMP, and the specific recognition and non-specific cleavage properties of CRISPR/Cas12a system, the dual-readout CRISPR/Cas12a biosensor was developed for sensitive and rapid detection of Salmonella enterica. Moreover, this platform in the detection of Salmonella enterica had limits of detection of 1 cfu/mL (colorimetric assay) in the linear range of 101-108 cfu/mL and 102 cfu/mL (lateral flow assay) in the linear range of 102-108 cfu/mL, respectively. Furthermore, the developed biosensor exhibited good recoveries in the spiked samples (lake water and milk) with varying concentrations of Salmonella enterica. This work provides new insights for the design of multifunctional nanozyme and the development of innovative dual-readout CRISPR/Cas system-based biosensing platform for the detection of pathogens.

Antibacterial action of slightly acidic electrolytic water against Cronobacter sakazakii and its application as a disinfectant on high-risk contact surfaces.

Powdered infant formula (PIF) is prone to Cronobacter sakazakii (C. sakazakii) contamination, which can result in infections that endanger the lives of newborns and infants. Slightly acidic electrolytic water (SAEW) has shown antibacterial effects on a variety of foodborne pathogens and has a wide applicability in the food industry. Here, the antibacterial activity of SAEW against C. sakazakii and its use as a disinfectant on contact surfaces with high infection transmission risk were investigated. The inactivation of SAEW on C. sakazakii was positively correlated to the SAEW concentration and treatment time. The antibacterial effect of SAEW was achieved by decreasing the intracellular adenosine triphosphate (ATP), K+, protein, and DNA contents of C. sakazakii, reducing the intracellular pH (pHin) and destroying the cell morphology, which led to inactivation of C. sakazakii ultimately. To test the applicability of this study, the results showed that approximately 103 CFU/cm2 of C. sakazakii were successfully inactivated on stainless steel and rubber surfaces after a 30 mg/L SAEW treatment for 20 s. These results indicate the antibacterial mechanism and potential application of SAEW against C. sakazakii, as well as a new strategy for the prevention and control of C. sakazakii on stainless steel and rubber surfaces.

The Immunomodulatory Effects of A2 ß-Casein on Immunosuppressed Mice by Regulating Immune Responses and the Gut Microbiota.

The aim of this study was to investigate the immunomodulatory effects of A2 ß-casein (ß-CN) in cyclophosphamide-induced immunosuppressed BALB/c mice. Experiments conducted in vitro revealed that A2 ß-CN digestive products have potent immunostimulatory activities. Animal studies demonstrated that A2 ß-CN improved the immunological organ index reduction trend caused by cyclophosphamide, reduced the pathological damage to the spleen tissue in immunosuppressed mice, increased the release of IL-17A, IgG, and IgA, and reduced the production of IL-4. By regulating the relative abundance of advantageous bacteria like Oscillospira, Lactobacillus, and Bifidobacteria and harmful bacteria like Coprococcus and Desulfovibrionaceae, A2 ß-CN improved gut microbiota disorders in immunosuppressed mice. Moreover, A2 ß-CN promoted the production of short-chain fatty acids and increased the diversity of the gut microbiota. Therefore, ingestion of A2 ß-CN is beneficial to the host's immune system and gut health. These findings provide insights for the future application of A2 ß-CN-related dairy products.

Effects of different reducing carbohydrate types on the physicochemical characteristics of infant formula food stored for special medical purposes.

The formula of food for special medical purpose has a direct impact on physicochemical stability, especially in hot climes and high temperature transport storage environments. An accelerated test (50 °C for 7 weeks) was used to analyze the mechanism of the physicochemical instability of formula A with lactose and maltodextrin, and formula B with maltodextrin. Deep dents and wrinkles were observed on the surface of the formula B, and more fat globules covered the surface of formula A particles after storage for a long time. Significantly higher amounts of furosine and Nε-carboxymethl-l-lysine (CML) were formed and the loss of available lysine was greater in formula A than in formula B. No significant difference was observed in lipid oxidation indicators between the two formulas. The results of this research demonstrated lactose was more active than maltodextrin and led to physicochemical instability.

Optical nanosensors based on noble metal nanoclusters for detecting food contaminants: A review.

Food contaminants present a significant threat to public health. In response to escalating global concerns regarding food safety, there is a growing demand for straightforward, rapid, and sensitive detection technologies. Noble metal nanoclusters (NMNCs) have garnered considerable attention due to their superior attributes compared to other optical materials. These attributes include high catalytic activity, excellent biocompatibility, and outstanding photoluminescence properties. These features render NMNCs promising candidates for crafting nanosensors for food contaminant detection, offering the potential for the development of uncomplicated, swift, sensitive, user-friendly, and cost-effective detection approaches. This review investigates optical nanosensors based on NMNCs, including the synthesis methodologies of NMNCs, sensing strategies, and their applications in detecting food contaminants. Furthermore, it involves a comparative assessment of the applications of NMNCs in optical sensing and their performance. Ultimately, this paper imparts fresh perspectives on the forthcoming challenges. Hitherto, optical (particularly fluorescent) nanosensors founded on NMNCs have demonstrated exceptional sensing capabilities in the realm of food contaminant detection. To enhance sensing performance, future research should prioritize atomically precise NMNCs synthesis, augmentation of catalytic activity and optical properties, development of high-throughput and multimode sensing, integration of NMNCs with microfluidic devices, and the optimization of NMNCs storage, shelf life, and transportation conditions.

Recent advances in the bovine ß-casein gene mutants on functional characteristics and nutritional health of dairy products: Status, challenges, and prospects.

ß-casein is the second most abundant form of casein in milk. Changes in amino acid sequence at specific positions in the primary structure of ß-casein in milk will produce gene mutations that affect the physicochemical properties of dairy products and the hydrolysis site of digestive enzymes. The screening method of ß-casein allele frequency detection in dairy products also has attracted the extensive attention of scientists and farmers. The A1 and A2 ß-casein is the two usual mutation types, distinguished by histidine and proline at position 67 in the peptide chain. This paper summarizes the effects of A1 and A2 ß-casein on the physicochemical properties of dairy products and evaluates the effects on human health, and the genotyping methods were also concluded. Impressively, this review presents possible future opportunities and challenges for the promising field of A2 ß-casein, providing a valuable reference for the development of the functional dairy market.

The probiotic fermented milk of Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 alleviates constipation via improving gastrointestinal motility and gut microbiota.

Constipation is directly related to the intestinal microenvironment, in which the promotion of gastrointestinal (GI) motility and improvement of gut microbiota distribution are important for alleviating symptoms. Herein, after the intervention of probiotic fermented milk (FMMIX) containing Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 for 14 d in Kunming mice with loperamide-induced constipation, the results indicated that FMMIX significantly increased the secretion of serum motilin, gastrin and 5-hydroxytryptamine, as well as decreased the secretion of peptide YY, vasoactive intestinal peptide, and nitric oxide in mice. As determined by immunohistochemical analysis, FMMIX promoted an augmentation in the quantity of Cajal interstitial cells. In addition, the mRNA and protein expression of c-kit and stem cell factor (SCF) were upregulated to facilitate intestinal motility. High-throughput sequencing and gas chromatography techniques revealed that FMMIX led to an increase in the relative abundance of beneficial bacteria (Lactobacillus, Oscillospira, Ruminococcus, Coprococcus, and Akkermansia), reduced the presence of harmful bacteria (Prevotella), and resulted in elevated levels of short-chain fatty acids (SCFA) with a superior improvement compared with unfermented milk. Untargeted metabolomics revealed significant upregulation of functional metabolites such as l-pipecolinic acid, dl-phenylalanine, and naringenin in FMMIX, presumably playing a potential role in constipation relief. Overall, our results showed that FMMIX had the potential to alleviate constipation symptoms in mice by improving the secretion of serum GI regulatory peptides and neurotransmitters, increasing the expression of c-kit and SCF proteins, and modulating the gut microbiota structure and SCFA levels, and may be associated with an increase in these functional metabolites. This suggested that FMMIX could be a promising adjunctive strategy for managing constipation symptoms and could contribute to the development of functional foods aimed at improving gut health.

Combating Obesity: Harnessing the Synergy of Postbiotics and Prebiotics for Enhanced Lipid Excretion and Microbiota Regulation.

Obesity is a chronic metabolic disease that can be induced by a high-fat diet (HFD) and predisposes to a variety of complications. In recent years, various bioactive substances, such as probiotics, prebiotics, and postbiotics, have been widely discussed because of their good anti-lipid and anti-inflammatory activities. In this paper, soybean protein isolate was used as a substrate to prepare the postbiotic. Compound prebiotics (galactose oligosaccharides, fructose oligosaccharides, and lactitol) preparation Aunulife Postbiotics and Prebiotics Composition (AYS) is the research object. Weight loss and bowel movements in mice induced by a high-fat diet were studied. Moreover, qualitative and quantitative analyses of small-molecule metabolites in AYS were performed to identify the functional molecules in AYS. After 12 weeks of feeding, the weight gain of mice that were fed with high-dose AYS (group H) and low-dose AYS (group L) from 4 to 12 weeks was 6.72 g and 5.25 g (p < 0.05), both of which were significantly lower than that of the high-fat diet (group DM, control group) group (7.73 g) (p < 0.05). Serum biochemical analysis showed that TC, TG, and LDL-C levels were significantly lower in mice from the H and L groups (p < 0.05). In addition, the fecal lipid content of mice in the L group reached 5.89%, which was significantly higher than that of the DM group at 4.02% (p < 0.05). The study showed that AYS changed the structure of the intestinal microbiota in mice on a high-fat diet, resulting in a decrease in the relative abundance of Firmicutes and Muribaculaceae and an increase in the relative abundance of Bacteroidetes, Verrucomicrobia, and Lactobacillus. The metabolomics study results of AYS showed that carboxylic acids and derivatives, and organonitrogen compounds accounted for 51.51% of the AYS metabolites, among which pantothenate, stachyose, betaine, and citrate had the effect of preventing obesity in mice. In conclusion, the administration of prebiotics and postbiotic-rich AYS reduces weight gain and increases fecal lipid defecation in obese mice, potentially by regulating the intestinal microbiota of mice on a high-fat diet.

Whole-transcriptome analysis after the acquisition of antibiotic resistance of Cronobacter sakazakii: Mechanisms of antibiotic resistance and virulence changes.

The emergence of antibiotic-resistant bacteria led to the misuse of antibiotics, resulting in the emergence of more resistant bacteria and continuous improvement in their resistance ability. Cronobacter sakazakii (C. sakazakii) has been considered a pathogen that harms infants. Incidents of C. sakazakii contamination have continued globally, several studies have indicated that C. sakazakii is increasingly resistant to antibiotics. A few studies have explored the mechanism of antibiotic resistance in C. sakazakii, and some have examined the antibiotic resistance and changes in virulence levels. We aimed to investigate the antibiotic resistance mechanism and virulence differences in C. sakazakii. The level of virulence factors of C. sakazakii was modified after induction by antibiotics compared with the antibiotic-sensitive strains, and the XS001-Ofl group had the strongest capacity to produce enterotoxin (85.18 pg/mL) and hemolysin (1.47 ng/mL). The biofilm formation capacity after induction significantly improved. The number of bases and mapped reads in all groups accounted for more than 55 % and 70 %, as detected by transcriptomic analysis. The resistance mechanism of different antibiotics was more common in efflux pumps, cationic antimicrobial peptides, and biofilm formation pathways. The level of antibiotic resistance mainly affected the expression of virulence genes associated with flagella assembly and synthesis.

Co-culture of Cronobacter sakazakii and Staphylococcus aureus: Explore the influence of mixed biofilm formation and regulation of Cronobacter sakazakii biofilm formation genes.

Bacterial biofilm is a protective matrix composed of metabolites secreted by bacteria that envelop bacteria. By forming a biofilm, bacteria can considerably improve their environmental tolerance. In food-related processing environment, different types of microorganisms are often present in biofilms. The main contaminating strain in the powdered infant formula (PIF) processing environment, Cronobacter sakazakii and Staphylococcus aureus continues to pollute the PIF processing environment after biofilm production. This study selected Cronobacter sakazakii with a weak biofilm-forming ability as one of the test organisms. The coexistence of Cronobacter sakazakii and Staphylococcus aureus on the surface of production equipment was simulated to analyze the interaction. Biofilm formation in the co-culture group was significantly higher than the others. In-depth study of the effect of Staphylococcus aureus on the biofilm formation genes of Cronobacter sakazakii. Results show two bacteria can coexist on the surface of a metal device, forming a more compact hybrid biofilm structure. Under co-culture conditions, S. aureus increased bcsA and fliD expression in Cronobacter sakazakii, whereas decreased bcsC expression. Signaling molecules produced by Staphylococcus aureus (Autoinducer 2) significantly promoted the biofilm formation of Cronobacter sakazakii at the concentration of 0-500 ng/mL (0.099-0.177) and up-regulated the expression of bcsA, filD and flhD genes.

Streptococcus thermophilus JM905-Strain Carbon Source Utilization and Its Fermented Milk Metabolic Profile at Different Fermentation Stages.

The metabolic utilization of different carbon sources by Streptococcus thermophilus JM905(S. thermophilus JM905) was determined using a high-throughput microbial phenotyping system, and changes in fermentation characteristics of S. thermophilus JM905 fermented milk were investigated at different fermentation periods, with changes in pH, water-holding capacity, viscosity, nuisance odor, and viable bacteria count being used to define the fermentation characteristics of the strain. Changes in the key metabolites, 2-hydroxybutyric acid, folic acid, L-lactic acid, D-glycerol-D-galactose-heptanol, (R)-leucine, L-aspartic acid, L-proline, D-arginine, L-isoleucine, hydra starch, L-lysine, L-tryptophan, and D-galactose, were clarified. Correspondingly, the fermented milk protein, amino acid, and fermented milk fat quality nutrient contents were determined to be 3.78 ± 0.054 g per 100 g, 3.405 ± 0.0234 g per 100 mL, and 0.161 ± 0.0030 g per 100 g, respectively. This study addressed strain carbon source utilization, changes in fermentation characteristics and metabolites during fermentation, with the aim of investigating the link between fermentation characteristics and metabolite quality components of Streptococcus thermophilus JM905 and its fermented milk with fermentation potential and to provide a useful reference for the screening of superior fermentation strains.

Effect of Thermostable Enzymes Produced by Psychrotrophic Bacteria in Raw Milk on the Quality of Ultra-High Temperature Sterilized Milk.

Ultra-high temperature sterilized milk (UHT) is a popular dairy product known for its long shelf life and convenience. However, protein gel aging and fat quality defects like creaming and flavor deterioration may arise during storage. These problems are primarily caused by thermostable enzymes produced by psychrotrophic bacteria. In this study, four representative psychrotrophic bacteria strains which can produce thermostable enzymes were selected to contaminate UHT milk artificially. After 11, 11, 13, and 17 weeks of storage, the milk samples, which were contaminated with Pseudomonas fluorescens, Chryseobacterium carnipullorum, Lactococcus raffinolactis and Acinetobacter guillouiae, respectively, demonstrated notable whey separation. The investigation included analyzing the protein and fat content in the upper and bottom layers of the milk, as well as examining the particle size, Zeta potential, and pH in four sample groups, indicating that the stability of UHT milk decreases over time. Moreover, the spoiled milk samples exhibited a bitter taste, with the dominant odor being attributed to ketones and acids. The metabolomics analysis revealed that three key metabolic pathways, namely ABC transporters, butanoate metabolism, and alanine, aspartate, and glutamate metabolism, were found to be involved in the production of thermostable enzymes by psychrotrophic bacteria. These enzymes greatly impact the taste and nutrient content of UHT milk. This finding provides a theoretical basis for further investigation into the mechanism of spoilage.

Comparative proteomics reveals the antibiotic resistance and virulence of Cronobacter isolated from powdered infant formula and its processing environment.

Cronobacter species are opportunistic foodborne pathogens that can cause neonatal meningitis, sepsis, and necrotizing enterocolitis. In this genus, certain level strains have high mortality to infant (Cronobacter sakazakii and Cronobacter malonaticus) and antibiotic tolerance. Cronobacter has strong environmental tolerance (acid resistance, high temperature resistance, UV resistance, antibiotic resistance, etc.) and can survive in a variety of environments. It has been isolated in various production environments and products in several countries. However, the relationships between Cronobacter antibiotic tolerance and virulence remain unclear, especially at the molecular level. In this study, 96 strains of Cronobacter were isolated from powdered infant formula and its processing environment and screened for antibiotic tolerance, and proteomic maps of the representative strains of Cronobacter with antibiotic tolerance were generated by analyzing proteomics data using multiple techniques to identify protein that are implicated in Cronobacter virulence and antibiotic resistance. The increase in antibiotic tolerance of Cronobacter had a certain increase in the production of enterotoxin and hemolysin. Only triple tolerated Cronobacter sakazakii decreased the utilization of sialic acid. A total of 16,131 intracellular proteins were detected in eight representative strains, and different proteomes were present in strains with different antibiotic tolerance, including 56 virulence-related proteins. Multiple virulence proteins regulated by unknown genes were also found in the eight isolated representative strains.

A Method to Directly Identify Cronobacter sakazakii in Liquid Medium by MALDI-TOF MS.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry has been widely used as an emerging technology for the rapid identification of microorganisms. Cronobacter sakazakii (C. sakazakii) is a food-borne pathogen of particular importance to the powdered infant formula (PIF) processing environment due to its high lethality in infants. However, the traditional solid spotting detection method of pretreating samples for MALDI-TOF MS leads only to qualitative detection of C. sakazakii. We developed a new, low-cost, robust liquid spotting pretreatment method and used a response surface methodology to optimize its parameters. The applicability, accuracy, and quantitative potential were measured for different types of samples. The optimal parameters of this method were as follows: a volume of 70% formic acid of 25 µL, treatment with ultrasound at 350 W for 3 min, and a volume of acetonitrile added of 75 µL. These conditions led to the highest identification score for C. sakazakii (1926.42 ± 48.497). This method was found to detect bacteria accurately and reproducibly. When 70 strains of C. sakazakii isolates were analyzed with this method, the identification accuracy was 100%. The detection limit of C. sakazakii in environmental and PIF samples was 4.1 × 101 cfu/mL and 2.72 × 103 cfu/mL, respectively.

Depletion of reactive oxygen species induced by beetroot (Beta vulgaris) extract leads to apoptosis-like death in Cronobacter sakazakii.

This research aimed to disclose the antibacterial activity of beetroot extract (Beta vulgaris) against Cronobacter sakazakii and its possible mechanisms. We evaluated its antibacterial activity by measuring the minimum inhibitory concentration (MIC) and time-kill kinetics. We also evaluated the intracellular ATP levels, bacterial apoptosis-like death (ALD), and reactive oxygen species (ROS) levels to reveal the possible antibacterial mechanisms. Our results showed that the MIC of beetroot extract against C. sakazakii was 25 mg/mL and C. sakazakii (approximately 8 log cfu/mL) was completely inhibited after treatment with 2 MIC of beetroot extract for 3 h. Beetroot extract reduced intracellular ATP levels and facilitated characteristics of ALD in C. sakazakii, such as membrane depolarization, increased intracellular Ca2+ levels, phosphatidylserine externalization, caspase-like protein activation, and DNA fragmentation. Additionally, and different from most bacterial ALD caused by the accumulation of ROS, beetroot extract reduced the intracellular ROS levels in C. sakazakii. Our experimental data provide a rationale for further research of bacterial ALD and demonstrate that beetroot extract can inhibit C. sakazakii in food processing environments.

Identification, Typing and Drug Resistance of Cronobacter spp. in Powdered Infant Formula and Processing Environment.

Cronobacter spp. is a food-borne pathogenic microorganism that can cause serious diseases such as meningitis, sepsis, and necrotizing colitis in infants and young children. Powdered infant formula (PIF) is one of the main contamination routes, in which the processing environment is an important source of pollution. In this investigation, 35 Cronobacter strains isolated from PIF and its processing environment were identified and typed by 16S rRNA sequencing and multilocus sequence typing (MLST) technology. A total of 35 sequence types were obtained, and three new sequence types were isolated for the first time. The antibiotic resistance was analyzed, showing that all isolates were resistant to erythromycin but sensitive to ciprofloxacin. Multi-drug resistant strains accounted for 68.57% of the total, among which Cronobacter strains with the strongest drug resistance reached 13 multiple drug resistance. Combined with transcriptomics, 77 differentially expressed genes related to drug resistance were identified. The metabolic pathways were deeply excavated, and under the stimulation of antibiotic conditions, Cronobacter strains can activate the multidrug efflux system by regulating the expression of chemotaxis-related genes, thus, secreting more drug efflux proteins to enhance drug resistance. The study of drug resistance of Cronobacter and its mechanism has important public health significance for the rational selection of existing antibacterial drugs, the development of new antibacterial drugs to reduce the occurrence of bacterial resistance, and the control and treatment of infections caused by Cronobacter.

The Probiotic Combination of Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 Alleviates Gastrointestinal Motility Disorder via Improving Gut Microbiota.

Probiotics have received wide attention as a potential way to alleviate gastrointestinal (GI) motility disorders. Herein, we investigated the effects of Lacticaseibacillus paracasei JY062, Lactobacillus gasseri JM1, and the probiotic combination at 5 × 109 CFU/mL on mice induced by loperamide and explored the possible underlying mechanisms in GI motility disorder. After two weeks of probiotic intervention, the results indicated that the probiotic combination alleviated GI motility disorder better. It increased the secretion of excitatory GI regulators motilin, gastrin, and 5-hydroxytryptamine (5-HT) and decreased the secretion of the inhibitory GI regulators peptide YY and nitric oxide (NO), except vasoactive intestinal peptide. 5-HT and NO were related to the mRNA expression of 5-HT4 receptor and nitric oxide synthase, respectively. The intervention of probiotic combination also increased the number of interstitial cells of Cajal and the expression of SCF/c-kit protein. In addition, it also increased the abundance of beneficial bacteria (Lactobacillus, Rikenellaceae, and Clostridiaceae_Clostridium) and improved the contents of short-chain fatty acids in cecum contents of mice. In conclusion, the probiotic combination of L. paracasei JY062 and L. gasseri JM1 has the potential to alleviate GI motility disorders by balancing intestinal homeostasis.