Dietary fiber; Gut microbiota; Immune pectin; Tryptophan metabolites; Biotechnology; Food Science; Biochemistry; Animal Science and Zoology
Abstract :
[en] [en] BACKGROUND: Pectin is a heteropolysaccharide that acts as an intestinal immunomodulator, promoting intestinal development and regulating intestinal flora in the gut. However, the relevant mechanisms remain obscure. In this study, pigs were fed a corn-soybean meal-based diet supplemented with either 5% microcrystalline cellulose (MCC) or 5% pectin for 3 weeks, to investigate the metabolites and anti-inflammatory properties of the jejunum.
RESULT: The results showed that dietary pectin supplementation improved intestinal integrity (Claudin-1, Occludin) and inflammatory response [interleukin (IL)-10], and the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) was down-regulated in the jejunum. Moreover, pectin supplementation altered the jejunal microbiome and tryptophan-related metabolites in piglets. Pectin specifically increased the abundance of Lactococcus, Enterococcus, and the microbiota-derived metabolites (skatole (ST), 3-indoleacetic acid (IAA), 3-indolepropionic acid (IPA), 5-hydroxyindole-3-acetic acid (HIAA), and tryptamine (Tpm)), which activated the aryl hydrocarbon receptor (AhR) pathway. AhR activation modulates IL-22 and its downstream pathways. Correlation analysis revealed the potential relationship between metabolites and intestinal morphology, intestinal gene expression, and cytokine levels.
CONCLUSION: In conclusion, these results indicated that pectin inhibits the inflammatory response by enhancing the AhR-IL22-signal transducer and activator of transcription 3 signaling pathway, which is activated through tryptophan metabolites.
Disciplines :
Agriculture & agronomy
Author, co-author :
Dang, Guoqi ; Université de Liège - ULiège > TERRA Research Centre ; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Wen, Xiaobin; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Zhong, Ruqing; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Wu, Weida; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Tang, Shanlong; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Li, Chong ; Université de Liège - ULiège > TERRA Research Centre ; The Key Laboratory of Feed Biotechnology of Ministry of Agriculture, National Engineering Research Center of Biological Feed, Feed Research Institute, Chinese Academy of Agricultural Sciences, No.12 Zhongguancun South Street, Haidian District, Beijing, 100081, China
Yi, Bao; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Chen, Liang; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. chenliang01@caas.cn
Zhang, Hongfu; State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. zhanghongfu@caas.cn
Schroyen, Martine ; Université de Liège - ULiège > Département GxABT > Animal Sciences (AS)
Language :
English
Title :
Pectin modulates intestinal immunity in a pig model via regulating the gut microbiota-derived tryptophan metabolite-AhR-IL22 pathway.
NSCF - National Natural Science Foundation of China
Funding text :
This work was supported by National Natural Science Foundation of China (NSFC) (31802072), China Scholarship Council (CSC NO. 202103250006), the Central Public-interest Scientific Institution Basal Research Fund (No. Y2022GH02 & PJ01618301), and State Key Laboratory of Animal Nutrition (2004DA125184G2102).
Wu H, Wang Y, Li H, Meng L, Zheng N, Wang J. Effect of food endotoxin on infant health. Toxins (Basel). 2021;13(5):298. 10.3390/toxins13050298.
Tang S, Chen Y, Deng F, Yan X, Zhong R, Meng Q, et al. Xylooligosaccharide-mediated gut microbiota enhances gut barrier and modulates gut immunity associated with alterations of biological processes in a pig model. Carbohydr Polym. 2022;294:119776. 10.1016/j.carbpol.2022.119776. DOI: 10.1016/j.carbpol.2022.119776
Bang SJ, Kim G, Lim MY, Song EJ, Jung DH, Kum JS, et al. The influence of in vitro pectin fermentation on the human fecal microbiome. AMB Express. 2018;8(1):98. 10.1186/s13568-018-0629-9. DOI: 10.1186/s13568-018-0629-9
Elshahed MS, Miron A, Aprotosoaie AC, Farag MA. Pectin in diet: interactions with the human microbiome, role in gut homeostasis, and nutrient-drug interactions. Carbohydr Polym. 2021;255:117388. 10.1016/j.carbpol.2020.117388. DOI: 10.1016/j.carbpol.2020.117388
Chung WS, Walker AW, Louis P, Parkhill J, Vermeiren J, Bosscher D, et al. Modulation of the human gut microbiota by dietary fibres occurs at the species level. BMC Biol. 2016;14:3. 10.1186/s12915-015-0224-3. DOI: 10.1186/s12915-015-0224-3
Maria-Ferreira D, Nascimento AM, Cipriani TR, Santana-Filho AP, Watanabe PDS, Sant Ana DMG, et al. Rhamnogalacturonan, a chemically-defined polysaccharide, improves intestinal barrier function in DSS-induced colitis in mice and human Caco-2 cells. Sci Rep. 2018;8(1):12261. 10.1038/s41598-018-30526-2. DOI: 10.1038/s41598-018-30526-2
Beukema M, Faas MM, de Vos P. The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier: impact via gut microbiota and direct effects on immune cells. Exp Mol Med. 2020;52(9):1364–76. 10.1038/s12276-020-0449-2. DOI: 10.1038/s12276-020-0449-2
Wilms E, Jonkers D, Savelkoul HFJ, Elizalde M, Tischmann L, de Vos P, et al. The impact of pectin supplementation on intestinal barrier function in healthy young adults and healthy elderly. Nutrients. 2019;11(7):1554. https://doi.org/10.3390/nu11071554.
Jiang T, Gao X, Wu C, Tian F, Lei Q, Bi J, et al. Apple-derived pectin modulates gut microbiota, improves gut barrier function, and attenuates metabolic endotoxemia in rats with diet-induced obesity. Nutrients. 2016;8(3):126. 10.3390/nu8030126. DOI: 10.3390/nu8030126
Sasaki H, Lyu Y, Nakayama Y, Nakamura F, Watanabe A, Miyakawa H, et al. Combinatorial effects of soluble, insoluble, and organic extracts from Jerusalem artichokes on gut microbiota in mice. Microorganisms. 2020;8(6):954. 10.3390/microorganisms8060954.
Zhang Q, Hu J, Feng JW, Hu XT, Wang T, Gong WX, et al. Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection. Genome Biol. 2020;21(1):99. 10.1186/s13059-020-02007-1. DOI: 10.1186/s13059-020-02007-1
Ichikawa-Seki M, Motooka D, Kinami A, Murakoshi F, Takahashi Y, Aita J, et al. Specific increase of Fusobacterium in the faecal microbiota of neonatal calves infected with Cryptosporidium parvum. Sci Rep. 2019;9(1):12517. 10.1038/s41598-019-48969-6. DOI: 10.1038/s41598-019-48969-6
Pilla R, Gaschen FP, Barr JW, Olson E, Honneffer J, Guard BC, et al. Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs. J Vet Intern Med. 2020;34(5):1853–66. 10.1111/jvim.15871. DOI: 10.1111/jvim.15871
Mills S, Stanton C, Lane JA, Smith GJ, Ross RP. Precision nutrition and the microbiome, part I: current state of the science. Nutrients. 2019;11(4):923. 10.3390/nu11040923.
Beukema M, Jermendi E, van den Berg MA, Faas MM, Schols HA, de Vos P. The impact of the level and distribution of methyl-esters of pectins on TLR2-1 dependent anti-inflammatory responses. Carbohydr Polym. 2021;251:117093. 10.1016/j.carbpol.2020.117093. DOI: 10.1016/j.carbpol.2020.117093
Krishnan R, Ko D, Foster CE 3rd, Liu W, Smink AM, de Haan B, et al. Immunological challenges facing translation of alginate encapsulated porcine islet xenotransplantation to human clinical trials. Methods Mol Biol. 2017;1479:305–33. 10.1007/978-1-4939-6364-5_24. DOI: 10.1007/978-1-4939-6364-5_24
Zhang LS, Davies SS. Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions. Genome Med. 2016;8(1):46. 10.1186/s13073-016-0296-x. DOI: 10.1186/s13073-016-0296-x
Scott SA, Fu J, Chang PV. Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor. P Natl Acad Sci USA. 2020. 10.1073/pnas.2000047117.
Mawe GM, Hoffman JM. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013;10(8):473–86. 10.1038/nrgastro.2013.105. DOI: 10.1038/nrgastro.2013.105
Wrzosek L, Ciocan D, Hugot C, Spatz M, Dupeux M, Houron C, et al. Microbiota tryptophan metabolism induces aryl hydrocarbon receptor activation and improves alcohol-induced liver injury. Gut. 2021;70(7):1299–308. 10.1136/gutjnl-2020-321565. DOI: 10.1136/gutjnl-2020-321565
Wu W, Zhang L, Xia B, Tang S, Xie J, Zhang H. Modulation of pectin on mucosal innate immune function in pigs mediated by gut microbiota. Microorganisms. 2020;8(4):535. 10.3390/microorganisms8040535.
National Research Council (NRC). Nutrient requirements of swine: Eleventh Revised Edition. Washington: the National Academy Press; 2012. 10.17226/13298.
Xia B, Wu W, Fang W, Wen X, Xie J, Zhang H. Heat stress-induced mucosal barrier dysfunction is potentially associated with gut microbiota dysbiosis in pigs. Anim Nutr. 2022;8(1):289–99. 10.1016/j.aninu.2021.05.012. DOI: 10.1016/j.aninu.2021.05.012
Wen X, Zhong R, Dang G, Xia B, Wu W, Tang S, et al. Pectin supplementation ameliorates intestinal epithelial barrier function damage by modulating intestinal microbiota in lipopolysaccharide-challenged piglets. J Nutr Biochem. 2022;10:9107. https://doi.org/10.1016/j.jnutbio.2022.109107.
Shrestha S, Noh JM, Kim SY, Ham HY, Kim YJ, Yun YJ, et al. Angiotensin converting enzyme inhibitors and angiotensin ii receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype. Oncoimmunology. 2016;5(1):e1067744. 10.1080/2162402X.2015.1067744. DOI: 10.1080/2162402X.2015.1067744
Wang T, Yao W, Li J, Shao Y, He Q, Xia J, et al. Dietary garcinol supplementation improves diarrhea and intestinal barrier function associated with its modulation of gut microbiota in weaned piglets. J Anim Sci Biotechnol. 2020;11:12. 10.1186/s40104-020-0426-6. DOI: 10.1186/s40104-020-0426-6
Yu C, Wu D, Zhu K, Hou L, Hang X, Ding T, et al. Challenges of pectic polysaccharides as a prebiotic from the perspective of fermentation characteristics and anti-colitis activity. Carbohydr Polym. 2021;270:118377. 10.1016/j.carbpol.2021.118377. DOI: 10.1016/j.carbpol.2021.118377
Xie J, Yu R, Qi J, Zhang G, Peng X, Luo J. Pectin and inulin stimulated the mucus formation at a similar level: an omics-based comparative analysis. J Food Sci. 2020;85(6):1939–47. 10.1111/1750-3841.15163. DOI: 10.1111/1750-3841.15163
Schanz O, Chijiiwa R, Cengiz SC, Majlesain Y, Weighardt H, Takeyama H, et al. Dietary AhR ligands regulate AhRR expression in intestinal immune cells and intestinal microbiota composition. Int J Mol Sci. 2020;21(9):3189. 10.3390/ijms21093189.
Abdollahi A, Karimi A, Sadeghi AA, Bedford MR, Ashengroph M. The effects of the fiber source and xylanase supplementation on production, egg quality, digestibility, and intestinal morphology in the aged laying hen. Poultry Sci. 2021;100(3):100936. 10.1016/j.psj.2020.12.033. DOI: 10.1016/j.psj.2020.12.033
Tejeda OJ, Kim WK. Effects of fiber type, particle size, and inclusion level on the growth performance, digestive organ growth, intestinal morphology, intestinal viscosity, and gene expression of broilers. Poultry Sci. 2021;100(10):101397. 10.1016/j.psj.2021.101397. DOI: 10.1016/j.psj.2021.101397
Wang Y, Lu WQ, Li DF, Liu XT, Wang HL, Niu S, et al. Energy and ileal digestible amino acid concentrations for growing pigs and performance of weanling pigs fed fermented or conventional soybean meal. Asian-Australas J Anim Sci. 2014;27(5):706–16. 10.5713/ajas.2013.13612. DOI: 10.5713/ajas.2013.13612
Stan TL, Soylu-Kucharz R, Burleigh S, Prykhodko O, Cao L, Franke N, et al. Increased intestinal permeability and gut dysbiosis in the r6/2 mouse model of Huntington’s disease. Sci Rep. 2020;10(1):18270. 10.1038/s41598-020-75229-9. DOI: 10.1038/s41598-020-75229-9
He J, Xie H, Chen D, Yu B, Huang Z, Mao X, et al. Synergetic responses of intestinal microbiota and epithelium to dietary inulin supplementation in pigs. Eur J Nutr. 2021;60(2):715–27. 10.1007/s00394-020-02284-3. DOI: 10.1007/s00394-020-02284-3
Sun Y, He Y, Wang F, Zhang H, de Vos P, Sun J. Low-methoxyl lemon pectin attenuates inflammatory responses and improves intestinal barrier integrity in caerulein-induced experimental acute pancreatitis. Mol Nutr Food Res. 2017;61(4):1600885. 10.1002/mnfr.201600885.
Sahasrabudhe NM, Beukema M, Tian L, Troost B, Scholte J, Bruininx E, et al. Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis. Front Immunol. 2018;9:383. 10.3389/fimmu.2018.00383. DOI: 10.3389/fimmu.2018.00383
Jermendi E, Beukema M, van den Berg MA, de Vos P, Schols HA. Revealing methyl-esterification patterns of pectins by enzymatic fingerprinting: beyond the degree of blockiness. Carbohydr Polym. 2022;277:118813. 10.1016/j.carbpol.2021.118813. DOI: 10.1016/j.carbpol.2021.118813
Patel P, Malipatlolla DK, Devarakonda S, Bull C, Rascon A, Nyman M, et al. Dietary oat bran reduces systemic inflammation in mice subjected to pelvic irradiation. Nutrients. 2020;12(8):2172. 10.3390/nu12082172.
Stankovic N, Surbatovic M, Stanojevic I, Simic R, Djuricic S, Milickovic M, et al. Possible cytokine biomarkers in pediatric acute appendicitis. Ital J Pediatr. 2019;45(1):125. 10.1186/s13052-019-0726-7. DOI: 10.1186/s13052-019-0726-7
Shi Y, Liu Z, Cui X, Zhao Q, Liu T. Intestinal vitamin D receptor knockout protects from oxazolone-induced colitis. Cell Death Dis. 2020;11(6):461. 10.1038/s41419-020-2653-3. DOI: 10.1038/s41419-020-2653-3
Fischer F, Romero R, Hellhund A, Linne U, Bertrams W, Pinkenburg O, et al. Dietary cellulose induces anti-inflammatory immunity and transcriptional programs via maturation of the intestinal microbiota. Gut Microbes. 2020;12(1):1–17. 10.1080/19490976.2020.1829962. DOI: 10.1080/19490976.2020.1829962
Chen Y, Xie Y, Zhong R, Liu L, Lin C, Xiao L, et al. Effects of xylo-oligosaccharides on growth and gut microbiota as potential replacements for antibiotic in weaning piglets. Front Microbiol. 2021;12:641172. 10.3389/fmicb.2021.641172. DOI: 10.3389/fmicb.2021.641172
Wu W, Zhang L, Xia B, Tang S, Liu L, Xie J, et al. Bioregional alterations in gut microbiome contribute to the plasma metabolomic changes in pigs fed with inulin. Microorganisms. 2020;8(1):111. 10.3390/microorganisms8010111.
Tang X, Zhang L, Fan C, Wang L, Fu H, Ren S, et al. Dietary fiber influences bacterial community assembly processes in the gut microbiota of Durco× Bamei crossbred pig. Front Microbiol. 2021;12:688554. 10.3389/fmicb.2021.688554. DOI: 10.3389/fmicb.2021.688554
Pu G, Li P, Du T, Niu Q, Fan L, Wang H, et al. Adding appropriate fiber in diet increases diversity and metabolic capacity of distal gut microbiota without altering fiber digestibility and growth rate of finishing pig. Front Microbiol. 2020;11:533. 10.3389/fmicb.2020.00533. DOI: 10.3389/fmicb.2020.00533
Jin J, Zhang L, Jia J, Chen Q, Yuan Z, Zhang X, et al. Effects of maternal low-protein diet on microbiota structure and function in the Jejunum of Huzhu Bamei suckling piglets. Animals (Basel). 2019;9(10):713. 10.3390/ani9100713.
Li A, Yang Y, Qin S, Lv S, Jin T, Li K, et al. Microbiome analysis reveals gut microbiota alteration of early-weaned Yimeng black goats with the effect of milk replacer and age. Microb Cell Factories. 2021;20(1):78. 10.1186/s12934-021-01568-5. DOI: 10.1186/s12934-021-01568-5
Flemer B, Warren RD, Barrett MP, Cisek K, Das A, Jeffery IB, et al. The oral microbiota in colorectal cancer is distinctive and predictive. Gut. 2018;67(8):1454–63. 10.1136/gutjnl-2017-314814. DOI: 10.1136/gutjnl-2017-314814
Kasai C, Sugimoto K, Moritani I, Tanaka J, Oya Y, Inoue H, et al. Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: terminal restriction fragment length polymorphism and next-generation sequencing analyses. Oncol Rep. 2016;35(1):325–33. 10.3892/or.2015.4398. DOI: 10.3892/or.2015.4398
Li P, Niu Q, Wei Q, Zhang Y, Ma X, Kim SW, et al. Microbial shifts in the porcine distal gut in response to diets supplemented with Enterococcus faecalis as alternatives to antibiotics. Sci Rep. 2017;7:41395. 10.1038/srep41395. DOI: 10.1038/srep41395
Chen B, Gao LL, Pan Q. Woody forages effect the intestinal bacteria diversity of golden pompano Trachinotus ovatus. AMB Express. 2018;8(1):29. 10.1186/s13568-018-0550-2. DOI: 10.1186/s13568-018-0550-2
Polansky O, Sekelova Z, Faldynova M, Sebkova A, Sisak F, Rychlik I. Important metabolic pathways and biological processes expressed by chicken cecal microbiota. Appl Environ Microb. 2015;82(5):1569–76. 10.1128/AEM.03473-15. DOI: 10.1128/AEM.03473-15
Stinson LF, Gay MCL, Koleva PT, Eggesbo M, Johnson CC, Wegienka G, et al. Human milk from atopic mothers has lower levels of short chain fatty acids. Front Immunol. 2020;11:1427. 10.3389/fimmu.2020.01427. DOI: 10.3389/fimmu.2020.01427
Dai ZL, Wu GY, Zhu WY. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci. 2011;16(5):1768–86. 10.2741/3820. DOI: 10.2741/3820
Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY. Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids. 2012;42(5):1597–608. 10.1007/s00726-011-0846-x. DOI: 10.1007/s00726-011-0846-x
Zelante T, Iannitti RG, Fallarino F, Gargaro M, De Luca A, Moretti S, et al. Tryptophan feeding of the IDO1-AhR axis in host-microbial symbiosis. Front Immunol. 2014;5:640. 10.3389/fimmu.2014.00640. DOI: 10.3389/fimmu.2014.00640
Zhang B, Xu Y, Liu S, Lv H, Hu Y, Wang Y, et al. Dietary supplementation of foxtail millet ameliorates colitis-associated colorectal cancer in mice via activation of gut receptors and suppression of the STAT3 pathway. Nutrients. 2020;12(8):2367. 10.3390/nu12082367.
Keszthelyi D, Troost FJ, Masclee AA. Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function. Neurogastroenterol Motil. 2009;21(12):1239–49. 10.1111/j.1365-2982.2009.01370.x. DOI: 10.1111/j.1365-2982.2009.01370.x
Wlodarska M, Luo C, Kolde R, d'Hennezel E, Annand JW, Heim CE, et al. Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation. Cell Host Microbe. 2017;22(1):25–37. 10.1016/j.chom.2017.06.007. DOI: 10.1016/j.chom.2017.06.007
Zhu X, Fu B, Dong M, Guo Y, Cao Z, Wu J. Effects of long-term antibiotic treatment on mice urinary aromatic amino acid profiles. Biosci Rep. 2021;41(1):BSR20203498. https://doi.org/10.1042/BSR20203498.
Lamas B, Natividad JM, Sokol H. Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunol. 2018;11(4):1024–38. 10.1038/s41385-018-0019-2. DOI: 10.1038/s41385-018-0019-2
Kundi ZM, Lee JC, Pihlajamaki J, Chan CB, Leung KS, So SSY, et al. Dietary fiber from oat and rye brans ameliorate Western diet-induced body weight gain and hepatic inflammation by the modulation of short-chain fatty acids, bile acids, and tryptophan metabolism. Mol Nutr Food Res. 2021;65(1):e1900580. 10.1002/mnfr.201900580. DOI: 10.1002/mnfr.201900580
Qian M, Liu J, Zhao D, Cai P, Pan C, Jia W, et al. Aryl hydrocarbon receptor deficiency in intestinal epithelial cells aggravates alcohol-related liver disease. Cell Mol Gastroenterol Hepatol. 2022;13(1):233–56. 10.1016/j.jcmgh.2021.08.014. DOI: 10.1016/j.jcmgh.2021.08.014
Alexeev EE, Lanis JM, Kao DJ, Campbell EL, Kelly CJ, Battista KD, et al. Microbiota-derived indole metabolites promote human and murine intestinal homeostasis through regulation of interleukin-10 receptor. Am J Pathol. 2018;188(5):1183–94. 10.1016/j.ajpath.2018.01.011. DOI: 10.1016/j.ajpath.2018.01.011
Dong F, Hao F, Murray IA, Smith PB, Koo I, Tindall AM, et al. Intestinal microbiota-derived tryptophan metabolites are predictive of ah receptor activity. Gut Microbes. 2020;12(1):1–24. 10.1080/19490976.2020.1788899. DOI: 10.1080/19490976.2020.1788899
Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013;39(2):372–85. https://doi.org/10.1016/j.immuni.2013.08.003.
Wang J, Wang P, Tian H, Tian F, Zhang Y, Zhang L, et al. Aryl hydrocarbon receptor/il-22/stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice. Innate Immun. 2018;24(5):297–306. 10.1177/1753425918785016. DOI: 10.1177/1753425918785016
Elshaer D, Moniruzzaman M, Yi TO, Zhi Q, Schreiber V, Begun J, et al. Facile synthesis of dendrimer like mesoporous silica nanoparticles to enhance targeted delivery of interleukin-22. Biomater Sci-UK. 2021;9(22):7402–11. https://doi.org/10.1039/D1BM01352A.