Microbial regulation of intestinal stem cell function: implications for alleviating intestinal injury of weaned piglets

1. Yu, Q. et al. Gasdermin-D-mediated epithelial-immune circuit synchronizes nutrient absorption and host defense in the small intestine. Immunity. 58, 2226–2240.e2227 (2025).

   Google Scholar 

2. Jiang, D. et al. Lmo3-expressing peri-isthmus progenitor cells sustain renewal and repair of the mammalian intestinal telocyte niche. Dev. Cell. 61, 178–192.e175 (2026).

   Google Scholar 

3. Chi, F. T. et al. Dietary cysteine enhances intestinal stemness via CD8⁺ T cell-derived IL-22. Nature. 647, 706–715 (2025).

4. Jiao, S., Zheng, Z. H., Zhuang, Y. M., Tang, C. L. & Zhang, N. F. Dietary medium-chain fatty acid and Bacillus in combination alleviate weaning stress of piglets by regulating intestinal microbiota and barrier function. J. Anim. Sci. 101, skac414 (2023).

   Google Scholar 

5. Pluske, J. R., Hampson, D. J. & Williams, I. H. Factors influencing the structure and function of the small intestine in the weaned pig: a review. Livest. Prod. Sci. 51, 215–236 (1997).

   Google Scholar 

6. Qin, Y.-C. et al. Early weaning inhibits intestinal stem cell expansion to disrupt the intestinal integrity of Duroc piglets via regulating the Keap1/Nrf2 signaling. Antioxidants. 13, 1188 (2024).

   Google Scholar 

7. Zheng, X. et al. Integrated metagenomic and metabolomics profiling reveals key gut microbiota and metabolites associated with weaning stress in piglets. Genes. 15, 970 (2024).

   Google Scholar 

8. Goyal, S. et al. Bacterial ADP-heptose triggers stem cell regeneration in the intestinal epithelium following injury. Cell Stem Cell. 32, 1235–1250.e1236 (2025).

   Google Scholar 

9. Zhao, X. et al. Inflammatory microenvironment-responsive microsphere vehicles modulating gut microbiota and intestinal inflammation for intestinal stem cell niche remodeling in inflammatory bowel disease. ACS Nano 19, 12063–12079 (2025).

   Google Scholar 

10. Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007 (2007).

    Google Scholar 

11. Gehart, H. & Clevers, H. Tales from the crypt: new insights into intestinal stem cells. Nat. Rev. Gastroenterol. Hepatol. 16, 19–34 (2019).

    Google Scholar 

12. Sophien, A. N. A. et al. Intestinal stem cells and gut microbiota therapeutics: hype or hope?. Front. Med. 10, 1195374 (2023).

    Google Scholar 

13. Beaumont, M. et al. Intestinal organoids in farm animals. Vet. Res. 52, 33 (2021).

    Google Scholar 

14. Chen, S.-M. et al. Pathways regulating intestinal stem cells and potential therapeutic targets for radiation enteropathy. Mol. Biomed. 5, 46 (2024).

    Google Scholar 

15. Arenas-Gómez, C. M., Garcia-Gutierrez, E., Escobar, J. S. & Cotter, P. D. Human gut homeostasis and regeneration: the role of the gut microbiota and its metabolites. Crit. Rev. Microbiol. 49, 764–785 (2022).

    Google Scholar 

16. Wallaeys, C., Garcia-Gonzalez, N. & Libert, C. Paneth cells as the cornerstones of intestinal and organismal health: a primer. EMBO Mol. Med. 15, e16427 (2022).

    Google Scholar 

17. Nath, A., Chakrabarti, P., Sen, S. & Barui, A. Reactive oxygen species in modulating intestinal stem cell dynamics and function. Stem Cell Rev. Rep. 18, 2328–2350 (2022).

    Google Scholar 

18. He, L. et al. Gut microbiota modulating intestinal stem cell differentiation. World J. Stem Cells 16, 619–622 (2024).

    Google Scholar 

19. Markandey, M. et al. Gut microbiota: sculptors of the intestinal stem cell niche in health and inflammatory bowel disease. Gut Microbes. 13, 1990827 (2021).

    Google Scholar 

20. Cui, C. et al. Nur77 as a novel regulator of Paneth cell differentiation and function. Mucosal Immunol. 17, 752–767 (2024).

    Google Scholar 

21. Qin, Y. -c et al. L-glutamate requires β-catenin signalling through Frizzled7 to stimulate porcine intestinal stem cell expansion. Cell. Mol. Life Sci. 79, 523 (2022).

    Google Scholar 

22. Wu, H. et al. Breed-driven microbiome heterogeneity regulates intestinal stem cell proliferation via lactobacillus-lactate-GPR81 signaling. Adv. Sci. 11, e2400058 (2024).

    Google Scholar 

23. Bajic, D. et al. Gut microbiota-derived propionate regulates the expression of Reg3 mucosal lectins and ameliorates experimental colitis in mice. J. Crohn’s. Colitis. 14, 1462–1472 (2020).

    Google Scholar 

24. Deng, F. et al. Gut microbial metabolite pravastatin attenuates intestinal ischemia/reperfusion injury through promoting IL-13 release from Type II Innate lymphoid cells via IL−33/ST2 signaling. Front. Immunol. 12, 704836 (2021).

    Google Scholar 

25. Kim, J.-E. et al. Gut microbiota promotes stem cell differentiation through macrophage and mesenchymal niches in early postnatal development. Immunity 55, 2300–2317.e2306 (2022).

    Google Scholar 

26. Feng, X. H. & Derynck, R. Specificity and versatility in TGF-β signaling through Smads. Annu. Rev. Cell Dev. Biol. 21, 659–693 (2005).

    Google Scholar 

27. Jacob, J.-M. et al. PDGFRα-induced stromal maturation is required to restrain postnatal intestinal epithelial stemness and promote defense mechanisms. Cell Stem Cell 29, 856–868.e855 (2022).

    Google Scholar 

28. McCarthy, N. et al. Smooth muscle contributes to the development and function of a layered intestinal stem cell niche. Dev. Cell 58, 550–564.e556 (2023).

    Google Scholar 

29. Wu, H. et al. Host-microbiota interaction in intestinal stem cell homeostasis. Gut Microbes. 16, 2353399 (2024).

    Google Scholar 

30. Dou, C. -x et al. L-Glutamate enables the EGFR-MEK-ERK-mTFB2 axis to enhance mitochondrial biogenesis in intestinal stem cells. Stem Cell Res. Ther. 16, 599 (2025).

    Google Scholar 

31. Corrêa, R. O. et al. Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium. Microbiome 11, 90 (2023).

    Google Scholar 

32. Yin, J.-T. et al. Astragalus membranaceus polysaccharide regulates small intestinal microbes and activates IL-22 signal pathway to promote intestinal stem cell regeneration in aging mice. Am. J. Chin. Med. 52, 513–539 (2024).

    Google Scholar 

33. Hou, Q. et al. Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22. Cell Death Differ. 25, 1657–1670 (2018).

    Google Scholar 

34. Wang, Y. et al. Interaction between intestinal mycobiota and microbiota shapes lung inflammation. iMeta 3, e241 (2024).

    Google Scholar 

35. Zhu, P. et al. Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons. Cell Res. 32, 555–569 (2022).

    Google Scholar 

36. Ma, N., Chen, X., Johnston, L. J. & Ma, X. Gut microbiota-stem cell niche crosstalk: a new territory for maintaining intestinal homeostasis. iMeta 1, e54 (2022).

37. Kaiko, G. E. et al. The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 165, 1708–1720 (2016).

    Google Scholar 

38. Ma, X. et al. Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway. eLife 12, RP92906 (2025).

    Google Scholar 

39. Kim, S. et al. Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development. Gut Microbes 13, 1–20 (2021).

    Google Scholar 

40. Seo, D. W., Hong, K. T., Lee, J. H., Lee, J. S. & Jeong, Y. T. Dual independent mechanisms underlying gut epithelial remodeling upon sugar substitute consumption. FASEB J. 39, e70374 (2025).

    Google Scholar 

41. Duan, C. et al. Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism. Gut Microbes 15, 2233149 (2023).

    Google Scholar 

42. Ahmed, I. et al. Dietary interventions ameliorate infectious colitis by restoring the microbiome and promoting stem cell proliferation in mice. Int. J. Mol. Sci. 23, 339 (2021).

    Google Scholar 

43. Farhadipour, M. et al. SCFAs switch stem cell fate through HDAC inhibition to improve barrier integrity in 3D intestinal organoids from patients with obesity. iScience 26, 108517 (2023).

    Google Scholar 

44. Cui, X. J. et al. A new capacity of gut microbiota: fermentation of engineered inorganic carbon nanomaterials into endogenous organic metabolites. Proc. Natl. Acad. Sci. USA 120, e2218739120 (2023).

    Google Scholar 

45. Eshleman, E. M. et al. Microbiota-derived butyrate restricts tuft cell differentiation via histone deacetylase 3 to modulate intestinal type 2 immunity. Immunity 57, 319–332.e316 (2024).

    Google Scholar 

46. Xie, J. et al. Short-chain fatty acids produced by Ruminococcaceae mediate α-linolenic acid promote intestinal stem cells proliferation. Mol. Nutr. Food Res. 66, e2100408 (2021).

    Google Scholar 

47. Yan, Z. et al. Revitalizing gut health: Liangxue Guyuan Yishen Decoction promotes Akkermansia muciniphila-induced intestinal stem cell recovery post-radiation in mice. Phytomedicine 132, 155888 (2024).

    Google Scholar 

48. MacDonald, B. T., Tamai, K. & He, X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev. Cell 17, 9–26 (2009).

    Google Scholar 

49. Li, Q. et al. Time-restricted feeding promotes glucagon-like peptide-1 secretion and regulates appetite via tryptophan metabolism of gut Lactobacillus in pigs. Gut Microbes 17, 2467185 (2025).

    Google Scholar 

50. Xie, L.-W. et al. Microbiota-derived I3A protects the intestine against radiation injury by activating AhR/IL-10/Wnt signaling and enhancing the abundance of probiotics. Gut Microbes 16, 2347722 (2024).

    Google Scholar 

51. Zhang, J. et al. The gut microbial metabolite indole-3-aldehyde alleviates impaired intestinal development by promoting intestinal stem cell expansion in weaned piglets. J. Anim. Sci. Biotechnol. 15, 150 (2024).

    Google Scholar 

52. Wei, W. et al. Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment. Cell Metab. 36, 466–483.e467 (2024).

    Google Scholar 

53. Zhu, S. & Pan, W. Microbial metabolite steers intestinal stem cell fate under stress. Cell Stem Cell 31, 591–592 (2024).

    Google Scholar 

54. Zhang, S. et al. Intestinal crypt microbiota modulates intestinal stem cell turnover and tumorigenesis via indole acetic acid. Nat. Microbiol. 10, 765–783 (2025).

    Google Scholar 

55. Sun, Z. et al. Qingchang Wenzhong Decoction accelerates intestinal mucosal healing through modulation of dysregulated gut microbiome, intestinal barrier and immune responses in mice. Front. Pharmacol. 12, 738152 (2021).

    Google Scholar 

56. Zhang, D. et al. Polysaccharide from aloe vera gel improves intestinal stem cells dysfunction to alleviate intestinal barrier damage via 5-HT. Food Res. Int. 214, 116675 (2025).

    Google Scholar 

57. Dong, X. C. et al. The dichotomous roles of microbial- modified bile acids 7-oxo-DCA and isoDCA in intestinal tumorigenesis. Proc. Natl. Acad. Sci. USA 121, e2317596121 (2024).

    Google Scholar 

58. Fu, T. et al. Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression. Cell Rep. 42, 112997 (2023).

    Google Scholar 

59. Li, T. et al. A gut microbiota-bile acid axis promotes intestinal homeostasis upon aspirin-mediated damage. Cell Host Microbe 32, 191–208.e199 (2024).

    Google Scholar 

60. Li, Y. et al. Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration. Protein Cell 15, 818–839 (2024).

    Google Scholar 

61. Hou, Y. et al. A diet-microbial metabolism feedforward loop modulates intestinal stem cell renewal in the stressed gut. Nat. Commun. 12, 271 (2021).

    Google Scholar 

62. Lee, H. et al. Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice. Gut Microbes 14, 2121580 (2022).

    Google Scholar 

63. Wang, J. H. et al. AhR ligands from metabolites promote piglet intestinal ILC3 activation and IL-22 secretion to inhibit PEDV infection. J. Virol. 98, e0103924 (2024).

    Google Scholar 

64. Wang, Y. et al. Akkermansia muciniphila exacerbates acute radiation–induced intestinal injury by depleting mucin and enhancing inflammation. ISME J. 19, wraf084 (2025).

    Google Scholar 

65. Beaumont, M. et al. Disruption of the primocolonizing microbiota alters epithelial homeostasis and imprints stem cells in the colon of neonatal piglets. FASEB J. 37, e23149 (2023).

    Google Scholar 

66. Abo, H. et al. Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration. Nat. Commun. 11, 513 (2020).

    Google Scholar 

67. Dang, H. et al. Maternal gut microbiota influence stem cell function in offspring. Cell Stem Cell 32, 246–262.e248 (2025).

    Google Scholar 

68. Gao, J., Tian, Q., Li, S., Zheng, L. & Zhou, Y. The impact of maternal high-fat diet on stem cell programming and disease susceptibility in offspring. Mol. Nutr. Food Res. 69, e70303 (2025).

    Google Scholar 

69. He, Y. et al. Prenatal supplementation with the gut-derived tryptophan metabolite indole-3-propionic acid alleviates colitis susceptibility in maternal immune-activated offspring mice. J. Adv. Res. 81, 211–222 (2026).

    Google Scholar 

70. Lim, A. I. et al. Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring. Science 373, eabf3002 (2021).

    Google Scholar 

71. Campbell, J. M., Crenshaw, J. D. & Polo, J. The biological stress of early weaned piglets. J. Anim. Sci. Biotechnol. 4, 19 (2013).

    Google Scholar 

72. Tang, X., Xiong, K., Fang, R. & Li, M. Weaning stress and intestinal health of piglets: a review. Front. Immunol. 13, 1042778 (2022).

    Google Scholar 

73. Han, X., Hu, X., Jin, W. & Liu, G. Dietary nutrition, intestinal microbiota dysbiosis and post-weaning diarrhea in piglets. Anim. Nutr. 17, 188–207 (2024).

    Google Scholar 

74. Li, Y. et al. Weaning stress perturbs gut microbiome and its metabolic profile in piglets. Sci. Rep. 8, 18068 (2018).

    Google Scholar 

75. Adhikari, B., Kim, S. W. & Kwon, Y. M. Characterization of microbiota associated with digesta and mucosa in different regions of gastrointestinal tract of nursery pigs. Int. J. Mol. Sci. 20, 1630 (2019).

    Google Scholar 

76. Arfken, A. M., Frey, J. F. & Summers, K. L. Temporal dynamics of the gut bacteriome and mycobiome in the weanling pig. Microorganisms 8, 868 (2020).

    Google Scholar 

77. Chen, L. et al. The maturing development of gut microbiota in commercial piglets during the weaning transition. Front. Microbiol. 8, 1688 (2017).

    Google Scholar 

78. Massacci, F. R. et al. Late weaning is associated with increased microbial diversity and Faecalibacterium prausnitzii abundance in the fecal microbiota of piglets. Anim. Microbiome 2, 2 (2020).

    Google Scholar 

79. Saladrigas-García, M. et al. Understanding host-microbiota interactions in the commercial piglet around weaning. Sci. Rep. 11, 23488 (2021).

    Google Scholar 

80. Tang, W. et al. Impairment of intestinal barrier function induced by early weaning via autophagy and apoptosis associated with gut microbiome and metabolites. Front. Immunol. 12, 804870 (2021).

    Google Scholar 

81. Gresse, R., Chaucheyras Durand, F., Dunière, L., Blanquet-Diot, S. & Forano, E. Microbiota composition and functional profiling throughout the gastrointestinal tract of commercial weaning piglets. Microorganisms 7, 343 (2019).

    Google Scholar 

82. Meng, Q. et al. Weaning alters intestinal gene expression involved in nutrient metabolism by shaping gut microbiota in pigs. Front. Microbiol. 11, 694 (2020).

    Google Scholar 

83. Guevarra, R. B. et al. The dynamics of the piglet gut microbiome during the weaning transition in association with health and nutrition. J. Anim. Sci. Biotechnol. 9, 54 (2018).

    Google Scholar 

84. Derrien, M., Vaughan, E. E., Plugge, C. M. & de Vos, W. M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54, 1469–1476 (2004).

    Google Scholar 

85. Lan, C. et al. Next-generation probiotic candidates targeting intestinal health in weaned piglets: both live and heat-killed Akkermansia muciniphila prevent pathological changes induced by enterotoxigenic Escherichia coli in the gut. Anim. Nutr. 17, 110–122 (2024).

    Google Scholar 

86. Verdile, N., Mirmahmoudi, R., Brevini, T. A. L. & Gandolfi, F. Evolution of pig intestinal stem cells from birth to weaning. Animal 13, 2830–2839 (2019).

    Google Scholar 

87. Tian, J. et al. Early weaning causes small intestinal atrophy by inhibiting the activity of intestinal stem cells: involvement of Wnt/β-catenin signaling. Stem Cell Res. Ther. 14, 65 (2023).

    Google Scholar 

88. Curry, S. M., Schwartz, K. J., Yoon, K. J., Gabler, N. K. & Burrough, E. R. Effects of porcine epidemic diarrhea virus infection on nursery pig intestinal function and barrier integrity. Vet. Microbiol. 211, 58–66 (2017).

    Google Scholar 

89. Costa, A. V. D. et al. Breastfeeding lifespan control of growth, maintenance, and metabolism of small intestinal epithelium. J. Cell. Physiol. 238, 2304–2315 (2023).

    Google Scholar 

90. Wang, X. et al. Impact of different feed intake levels on intestinal morphology and epithelial cell differentiation in piglets. J. Anim. Sci. 103, skae262 (2025).

    Google Scholar 

91. Tian, J. et al. Glutamine boosts intestinal stem cell-mediated small intestinal epithelial development during early weaning: Involvement of WNT signaling. Stem Cell Rep. 18, 1451–1467 (2023).

    Google Scholar 

92. Moore, S. R. et al. Glutamine and alanyl-glutamine promote crypt expansion and mTOR signaling in murine enteroids. Am. J. Physiol. Gastrointest. Liver Physiol. 308, G831–G839 (2015).

    Google Scholar 

93. Fu, Y. et al. Paneth cells protect against acute pancreatitis via modulating gut microbiota dysbiosis. mSystems 7, e0150721 (2022).

    Google Scholar 

94. Feng, C. et al. Vitamin B12 ameliorates gut epithelial injury via modulating the HIF-1 pathway and gut microbiota. Cell. Mol. Life Sci. 81, 397 (2024).

    Google Scholar 

95. Gresse, R. et al. Gut microbiota dysbiosis in postweaning piglets: understanding the keys to health. Trends Microbiol. 25, 851–873 (2017).

    Google Scholar 

96. Yan, H. et al. Mulberry leaf benefits the intestinal epithelial barrier via direct anti-oxidation and indirect modulation of microbiota in pigs. Phytomedicine 135, 156217 (2024).

    Google Scholar 

97. Qin, W. et al. Dietary berberine and ellagic acid supplementation improve growth performance and intestinal damage by regulating the structural function of gut microbiota and SCFAs in weaned piglets. Microorganisms 11, 1254 (2023).

    Google Scholar 

98. Qin, W. et al. Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets. Anim. Nutr. 11, 322–333 (2022).

    Google Scholar 

99. Han, M. et al. Dietary grape seed proanthocyanidins (GSPs) improve weaned intestinal microbiota and mucosal barrier using a piglet model. Oncotarget 7, 80313–80326 (2016).

    Google Scholar 

100. Chen, J. et al. Metasilicate-based alkaline mineral water improves the growth performance of weaned piglets by maintaining gut-liver axis homeostasis through microbiota-mediated secondary bile acid pathway. Anim. Nutr. 20, 95–109 (2025).

     Google Scholar 

101. Chen, J. et al. Metasilicate-based alkaline mineral water confers diarrhea resistance in maternally separated piglets via the microbiota-gut interaction. Pharmacol. Res. 187, 106580 (2023).

     Google Scholar 

102. Chen, J. et al. Drinking alkaline mineral water confers diarrhea resistance in maternally separated piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis. J. Adv. Res. 52, 29–43 (2023).

     Google Scholar 

103. Liu, X. Y. et al. Garlic-derived exosome-like nanoparticles enhance gut homeostasis in stressed piglets: involvement of Lactobacillus reuteri modulation and indole-3-propionic acid induction. J. Agric. Food Chem. 73, 7228–7243 (2025).

     Google Scholar 

104. Luo, Y. et al. Gut-derived indole propionic acid alleviates liver fibrosis by targeting profibrogenic macrophages via the gut‒liver axis. Cell. Mol. Immunol. 22, 1414–1426 (2025).

     Google Scholar 

105. Choudhury, R., Gu, Y., Bolhuis, J. E. & Kleerebezem, M. Early feeding leads to molecular maturation of the gut mucosal immune system in suckling piglets. Front. Immunol. 14, 1208891 (2023).

     Google Scholar 

106. Boston, T. E. et al. Prebiotic galactooligosaccharide improves piglet growth performance and intestinal health associated with alterations of the hindgut microbiota during the peri-weaning period. J. Anim. Sci. Biotechnol. 15, 88 (2024).

     Google Scholar 

107. Choudhury, R. et al. Early life feeding accelerates gut microbiome maturation and suppresses acute post-weaning stress in piglets. Environ. Microbiol. 23, 7201–7213 (2021).

     Google Scholar 

108. Tian, S. Y., Wang, J., Wang, J. & Zhu, W. Y. Differential effects of early-life and postweaning galacto-oligosaccharide intervention on colonic bacterial composition and function in weaning piglets. Appl. Environ. Microbiol. 88, e0131821 (2022).

     Google Scholar 

109. Hayakawa, T., Masuda, T., Kurosawa, D. & Tsukahara, T. Dietary administration of probiotics to sows and/or their neonates improves the reproductive performance, incidence of post-weaning diarrhea and histopathological parameters in the intestine of weaned piglets. Anim. Sci. J. 87, 1501–1510 (2016).

     Google Scholar 

110. Hu, T. et al. Maternal probiotic mixture supplementation optimizes the gut microbiota structure of offspring piglets through the gut–breast axis. Anim. Nutr. 19, 386–400 (2024).

     Google Scholar 

111. Lu, D. et al. Maternal dietary inulin intake during late gestation and lactation ameliorates intestinal oxidative stress in piglets with the involvements of gut microbiota and bile acids metabolism. Anim. Nutr. 20, 318–331 (2025).

     Google Scholar 

112. Meurens, F., Summerfield, A., Nauwynck, H., Saif, L. & Gerdts, V. The pig: a model for human infectious diseases. Trends Microbiol. 20, 50–57 (2012).

     Google Scholar 

113. Xiao, L. et al. A reference gene catalogue of the pig gut microbiome. Nat. Microbiol. 1, 16161 (2016).

     Google Scholar 

114. Bozzetti, V. & Senger, S. Organoid technologies for the study of intestinal microbiota–host interactions. Trends Mol. Med. 28, 290–303 (2022).

     Google Scholar 

115. O’Toole, P. W., Marchesi, J. R. & Hill, C. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat. Microbiol. 2, 17057 (2017).

     Google Scholar 

116. Bindels, L. B., Delzenne, N. M., Cani, P. D. & Walter, J. Towards a more comprehensive concept for prebiotics. Nat. Rev. Gastroenterol. Hepatol. 12, 303–310 (2015).

     Google Scholar 

117. Rychen, G. et al. Guidance on the characterisation of microorganisms used as feed additives or as production organisms. EFSA J. 16, e05206 (2018).

     Google Scholar 

118. Salminen, S. et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat. Rev. Gastroenterol. Hepatol. 18, 649–667 (2021).

     Google Scholar 

119. Swanson, K. S. et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat. Rev. Gastroenterol. Hepatol. 17, 687–701 (2020).

     Google Scholar 

120. Pariza, M. W., Gillies, K. O., Kraak-Ripple, S. F., Leyer, G. & Smith, A. B. Determining the safety of microbial cultures for consumption by humans and animals. Regul. Toxicol. Pharmacol. 73, 164–171 (2015).

     Google Scholar 

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