Irritable bowel syndrome in children: pathogenetic significance of disorders of intestinal microbiota
https://doi.org/10.46563/1560-9561-2024-27-1-49-54
EDN: xqpypx
Abstract
Irritable bowel syndrome (IBS) is the most common functional disorder of the intestine in children. In recent years, IBS has been defined as functional pathology of the intestine, manifested by visceral recurrent pain that occurs at least once per week, characterized by the following two or more signs: associated with defecation; with changes in the frequency and shape of stools. These symptoms had to be noted in the patient for the last 3 months, with a total duration of at least 6 months, without signs of organic damage to the gastrointestinal tract (GIT). The gut microbiota is of particular importance in the pathogenesis of IBS. In patients with IBS, an increase in Enterobacteriaceae, Ruminococcus, Clostridium, Dorea species and a decrease in the number of Lactobacillus, Bifidobacterium and Faecalibacterium species were found. At the same time, a similar microbial profile was found in patients with different subtypes of IBS. The established patterns of changes in the composition of the microbiota in IBS in children and adults indicate IBS and functional disorders of the GIT to have a pronounced microbial pathogenesis. In this regard, the personalized use of prebiotics, probiotics, synbiotics, and fecal microbiota transplantation can effectively affect the intestinal microbiome in IBS.
Conclusion. Correction of disorders of intestinal microbiota is the most important method of treating IBS in children. Determining the patterns of formation of changes in the intestinal microbiome in IBS children creates new opportunities for improving methods of their correction.
Contribution:
Smirnova G.I. — concept and design of the study;
Smirnova G.I., Labinov V.S. — collection and processing of the material; writing the text;
Korsunsky A.A. — editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.
Acknowledgment. The study had no sponsorship.
Conflict of interest. The authors declare no conflict of interest.
Received: January 15, 2023
Accepted: January 30, 2024
Published: February 28, 2024
About the Authors
Galina I. SmirnovaRussian Federation
MD, PhD, DSci., Prof., professor of the Department of pediatrics and pediatric infectious diseases of the Sechenov University, Moscow, 119991, Russian Federation
e-mail: @yandex.ru
Vladimir S. Labinov
Russian Federation
Anatoliy A. Korsunskiy
Russian Federation
References
1. Chey W.D., Kurlander J., Eswaran S. Irritable bowel syndrome: a clinical review. JAMA. 2015; 313(9): 949–58. https://doi.org/10.1001/jama.2015.0954
2. Canavan C., West J., Timothy Card T. The epidemiology of irritable bowel syndrome. Clin. Epidemiol. 2014: 6: 71–80. https://doi.org/10.2147/CLEP.S40245
3. Smirnova G.I., Korsunskiy A.A., Lyalikova V.B. Irritable bowel syndrome in children: new in diagnostics and treatment. Rossiyskiy pediatricheskiy zhurnal. 2016; 19(5): 309–18. https://doi.org/10.18821/1560-95612016-19(5)-309-318 https://elibrary.ru/wrlfxv (in Russian)
4. Adriani A., Ribaldone D.G., Astegiano M., Durazzo M., Saracco G.M., Pellicano R. Irritable bowel syndrome: the clinical approach. Panminerva Med. 2018; 60(4): 213–22. https://doi.org/10.23736/S0031-0808.18.03541-3
5. Sebastián Domingo J.J. Irritable bowel syndrome. Med. Clin. (Barc.). 2022; 158(2): 76–81. https://doi.org/10.1016/j.medcli.2021.04.029
6. Van den Houte K., Carbone F., Pannemans J., Corsetti M., Fischler B., Piessevaux H., et al. Prevalence and impact of self-reported irritable bowel symptoms in the general population. United European Gastroenterol. J. 2019; 7(2): 307–15. https://doi.org/10.1177/2050640618821804
7. Holtmann G.J., Ford A.C., Talley N.J. Pathophysiology of irritable bowel syndrome. Lancet Gastroenterol. Hepatol. 2016; 1(2): 133–46. https://doi.org/10.1016/S2468-1253(16)30023-1
8. Defrees D.N., Bailey J. Irritable bowel syndrome: epidemiology, pathophysiology, diagnosis, and treatment. Prim. Care. 2017; 44(4): 655–71. https://doi.org/10.1016/j.pop.2017.07.009
9. Xiao L., Liu Q., Luo M., Xiong L. Gut microbiota-derived metabolites in irritable bowel syndrome. Front. Cell. Infect. Microbiol. 2021; 11: 729346. https://doi.org/10.3389/fcimb.2021.729346
10. Devanarayana N.M., Rajindrajith S., Pathmeswaran A., Abegunasekara C., Gunawardena N.K., Benninga M.A. Epidemiology of irritable bowel syndrome in children and adolescents in Asia. J. Pediatr. Gastroenterol. Nutr. 2015; 60(6): 792–8. https://doi.org/10.1097/MPG.0000000000000714
11. Lacy B.E., Patel N.K. Rome criteria and a diagnostic approach to irritable bowel syndrome. J. Clin. Med. 2017; 6(11): 99. https://doi.org/10.3390/jcm6110099.3
12. Barbara G., Cremon C., Bellini M., Corsetti M., Di Nardo G., Falangone F., et al. Italian guidelines for the management of irritable bowel syndrome. Dig. Liver Dis. 2023; 55(2): 187–207. https://doi.org/10.1016/j.dld.2022.11.015
13. Yan M., Man S., Sun B., Ma L., Guo L., Huang L., et al. Gut liver brain axis in diseases: the implications for therapeutic interventions. Signal Transduct. Target. Ther. 2023; 8(1): 443. https://doi.org/10.1038/s41392-023-01673-4
14. Okawa Y. A discussion of whether various lifestyle changes can alleviate the symptoms of irritable bowel syndrome. Healthcare (Basel). 2022; 10(10): 2011. https://doi.org/10.3390/healthcare10102011.2-4
15. Alshammari S.A., Almutairi M.N., Alomar M.O., Alsherif Z.M., Alsubaie F.H., Almezaini A.I. Overlap between gastroesophageal reflux disease and irritable bowel syndrome and its impact on quality of life. Cureus. 2023; 15(12): e50840. https://doi.org/10.7759/cureus.50840
16. Lu M., Wang Z. Microbiota and aging. Adv. Exp. Med. Biol. 2018; 1086: 141–56. https://doi.org/10.1007/978-981-13-1117-8_9
17. Nurko S., Saps M., Kossowsky J., Zion S.R., Di Lorenzo C., Vaz K., et al. Effect of Open-label placebo on children and adolescents with functional abdominal pain or irritable bowel syndrome: A randomized clinical trial. JAMA Pediatr. 2022; 176(4): 349–56. https://doi.org/10.1001/jamapediatrics.2021.5750
18. Acharya K., Bhardwaj V., Chuahan I., Mushfiq S., Bhatt S., Lamba B.M. Comparison of fecal calprotectin with different endoscopic scores in the assessment of ulcerative colitis (UC) activity and its utility in differentiating IBS from IBD. Euroasian J. Hepatogastroenterol. 2023; 13(2): 120–3. https://doi.org/10.5005/jp-journals-10018-1411
19. Zeng Y., Liu H., Pei Z., Li R., Liu Z., Liao C. Evaluation of the causal effects of blood metabolites on irritable bowel syndrome: Mendelian randomization. BMC Gastroenterol. 2024; 24(1): 19. https://doi.org/10.1186/s12876-023-03111-9
20. Krishnamurthy H.K., Pereira M., Bosco J., George J., Jayaraman V., Krishna K., et al. Gut commensals and their metabolites in health and disease. Front. Microbiol. 2023; 14: 1244293. https://doi.org/10.3389/fmicb.2023.1244293
21. Mayer E.A., Ryu H.J., Bhatt R.R. The neurobiology of irritable bowel syndrome. Mol. Psychiatry. 2023; 28(4): 1451–65. https://doi.org/10.1038/s41380-023-01972-w
22. Theodorou V., Ait Belgnaoui A., Agostini S., Eutamene H. Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome. Gut Microbes. 2014; 5(3): 430–6. https://doi.org/10.4161/gmic.29796
23. Lin Z., Wang Y., Lin S., Liu D., Mo G., Zhang H., et al. Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach. Gastroenterol. 2021; 21(1): 48. https://doi.org/10.1186/s12876-021-01626-7
24. Chen Y., Le D., Xu J., Jin P., Zhang Y., Liao Z. Gut microbiota dysbiosis and inflammation dysfunction in late-life depression: An observational cross-sectional analysis. Neuropsychiatr. Dis. Treat. 2024; 20: 399–414. https://doi.org/10.2147/NDT.S449224
25. Napolitano M., Fasulo E., Ungaro F., Massimino L., Sinagra E., Danese S., et al. Gut dysbiosis in irritable bowel syndrome: A narrative review on correlation with disease subtypes and novel therapeutic implications. Microorganisms. 2023; 11(10): 2369. https://doi.org/10.3390/microorganisms11102369
26. Mishima Y., Ishihara S. Molecular mechanisms of microbiota-mediated pathology in irritable bowel syndrome. Int. J. Mol. Sci. 2020; 21(22): 8664. https://doi.org/10.3390/ijms21228664
27. Mishima Y., Ishihara S. Enteric microbiota-mediated serotonergic signaling in pathogenesis of irritable bowel syndrome. Int. J. Mol. Sci. 2021; 22(19): 10235. https://doi.org/10.3390/ijms221910235
28. Zhao Y., Zou D.W. Gut microbiota and irritable bowel syndr. J. Dig. Dis. 2023; 24(5): 312–20. https://doi.org/10.1111/1751-2980.13204
29. Moloney R.D., Johnson A.C., O’Mahony S.M., Dinan T.G., Greenwood-Van Meerveld B., Cryan J.F. Stress and the microbiota-gut-brain axis in visceral pain: relevance to irritable bowel syndrome. CNS Neurosci. Ther. 2016; 22(2): 102–17. https://doi.org/10.1111/cns.12490
30. Pak R., Cho M., Pride K., Abd-Elsayed A. The gut microbiota and chronic pain. Curr. Pain Headache Rep. 2024; 28(4): 259–69. https://doi.org/10.1007/s11916-024-01221-x
31. Hillestad E.M.R., van der Meeren A., Nagaraja B.H., Bjørsvik B.R., Haleem N., Benitez-Paez A., et al. Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome. World J. Gastroenterol. 2022; 28(4): 412–31. https://doi.org/10.3748/wjg.v28.i4.412
32. Aziz M.N.M., Kumar J., Nawawi M.K.N., Ali R.A., Mokhtar N.M. Irritable bowel syndrome, depression, and neurodegeneration: A bidirectional communication from gut to Brain. Nutrients. 2021; 13(9): 3061. https://doi.org/10.3390/nu13093061
33. Riehl L., Fürst J., Kress M., Rykalo N. The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders. Front. Neurosci. 2024; 17: 1302957. https://doi.org/10.3389/fnins.2023.1302957
34. Pellissier S., Bonaz B. The place of stress and emotions in the irritable bowel syndrome. Vitam. Horm. 2017; 103: 327–54. https://doi.org/10.1016/bs.vh.2016.09.005
35. Roberts C., Albusoda A., Farmer A.D., Aziz Q. Factors influencing rectal hypersensitivity in irritable bowel syndrome: A systematic review and meta-analysis. Neurogastroenterol. Motil. 2023; 35(4): e14515. https://doi.org/10.1111/nmo.14515
36. Han L., Zhao L., Zhou Y., Yang C., Xiong T., Lu L., et al. Altered metabolome and microbiome features provide clues in understanding irritable bowel syndrome and depression comorbidity. ISME J. 2022; 16(4): 983–96. https://doi.org/10.1038/s41396-021-01123-5
37. Jacobs J.P., Gupta A., Bhatt R.R., Brawer J., Gao K., Tillisch K., et al. Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome. 2021; 9(1): 236. https://doi.org/10.1186/s40168-021-01188-6
38. Wilmes L., Collins J.M., O’Riordan K.J., O’Mahony S.M., Cryan J.F., Clarke G. Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome. Neurogastroenterol. Motil. 2021; 33(3): e14095. https://doi.org/10.1111/nmo.14095
39. Brierley S.M., Greenwood-Van Meerveld B., Sarnelli G., Sharkey K.A., Storr M., Tack J. Targeting the endocannabinoid system for the treatment of abdominal pain in irritable bowel syndrome. Nat. Rev. Gastroenterol. Hepatol. 2023; 20(1): 5–25. https://doi.org/10.1038/s41575-022-00682-y
40. Bayrer J.R., Castro J., Venkataraman A., Touhara K.K., Rossen N.D., Morrie R.D., et al. Gut enterochromaffin cells drive visceral pain and anxiety. Nature. 2023; 616(7955): 137–42. https://doi.org/10.1038/s41586-023-05829-8
41. von dem Knesebeck O., Löwe B., Lüdecke D., Bobardt J.S., Barbek R. Public knowledge and beliefs about the irritable bowel syndrome – results from the SOMA.SOC study. BMC Public Health. 2024; 24(1): 219. https://doi.org/10.1186/s12889-024-17784-8
42. Mandal R.S., Saha S., Das S. Metagenomic surveys of gut microbiota. Genomics Proteomics Bioinformatics. 2015; 13(3): 148–58. https://doi.org/10.1016/j.gpb.2015.02.005
43. Smirnova G.I., Mankute G.R. Intestinal microbiota and atopic dermatitis in children. Rossiyskiy pediatricheskiy zhurnal. 2015; 18(6): 46–53. https://elibrary.ru/vkgooj (in Russian)
44. Dothel G., Barbaro M.R., Di Vito A., Ravegnini G., Gorini F., Monesmith S., et al. New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics. J. Gastroenterol. 2023; 58(7): 605–21. https://doi.org/10.1007/s00535-023-01997-6
45. Chen M., Ruan G., Chen L., Ying S., Li G., Xu F., et al. Neurotransmitter and intestinal interactions: focus on the microbiota-gut-brain axis in irritable bowel syndrome. Front. Endocrinol. (Lausanne). 2022; 13: 817100. https://doi.org/10.3389/fendo.2022.817100
46. Wei W., Wang H.F., Zhang Y., Zhang Y.L., Niu B.Y., Yao S.K. Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome. World J. Gastroenterol. 2020; 26(45): 7153–72. https://doi.org/10.3748/wjg.v26.i45.7153
47. Su Q., Tun H.M., Liu Q., Yeoh Y.K., Mak J.W.Y., Chan F.K., et al. Gut microbiome signatures reflect different subtypes of irritable bowel syndrome. Gut Microbes. 2023; 15(1): 2157697. https://doi.org/10.1080/19490976.2022.2157697
48. Rurgo S., Vaino V., Andreozzi M., Pagliaro M., Senneca P., Di Giorgio G., et al. Predictors of abdominal pain severity in patients with constipation prevalent irritable bowel syndrome. J. Basic Clin. Physiol. Pharmacol. 2022; 33(5): 665–71. https://doi.org/10.1515/jbcpp-2022-0081
49. Martín R., Rios-Covian D., Huillet E., Auger S., Khazaal S., Bermúdez-Humarán L.G., et al. Faecalibacterium: a bacterial genus with promising human health applications. FEMS Microbiol. Rev. 2023; 47(4): fuad039. https://doi.org/10.1093/femsre/fuad039
50. Lupu V.V., Ghiciuc C.M., Stefanescu G., Mihai C.M., Popp A., Sasaran M.O., et al. Emerging role of the gut microbiome in post-infectious irritable bowel syndrome: A literature review. World J. Gastroenterol. 2023; 29(21): 3241–56. https://doi.org/10.3748/wjg.v29.i21.3241
51. Aguilera-Lizarraga J., Hussein H., Boeckxstaens G.E. Immune activation in irritable bowel syndrome: what is the evidence? Nat. Rev. Immunol. 2022; 22(11): 674–86. https://doi.org/10.1038/s41577-022-00700-9
52. Fuentes I.M., Christianson J.A. Ion channels, ion channel receptors, and visceral hypersensitivity in irritable bowel syndrome. Neurogastroenterol. Motil. 2016; 28(11): 1613–8. https://doi.org/10.1111/nmo.12979
53. Carco C., Young W., Gearry R.B., Talley N.J., McNabb W.C., Roy N.C. Increasing evidence that irritable bowel syndrome and functional gastrointestinal disorders have a microbial pathogenesis. Front. Cell. Infect. Microbiol. 2020; 10: 468. https://doi.org/10.3389/fcimb.2020.00468
54. Zyoud S.H., Smale S., Waring W.S., Sweileh W., Al-Jabi S.W. Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study. World J. Gastroenterol. 2021; 27(13): 1341–53. https://doi.org/10.3748/wjg.v27.i13.1341
55. Smirnova G.I., Lyalikova V.B. Irritable Bowel Syndrome in Children. A Textbook for Doctors [Sindrom razdrazhennogo kishechnika u detey. Uchebnoe posobie dlya vrachey]. Moscow; 2016. (in Russian)
56. Lacy B.E., Pimentel M., Brenner D.M., Chey W.D., Keefer L.A., Long M.D., et al. ACG clinical guideline: Management of irritable bowel syndrome. Am. J. Gastroenterol. 2021; 116(1): 17–44. https://doi.org/10.14309/ajg.0000000000001036
57. Vedantam S., Graff E., Khakoo N.S., Khakoo N.S., Pearlman M. Food as medicine: How to influence the microbiome and improve symptoms in patients with irritable bowel syndrome. Curr. Gastroenterol. Rep. 2023; 25(3): 52–60. https://doi.org/10.1007/s11894-023-00861-0
58. Black C.J., Staudacher H.M., Ford A.C. Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. Gut. 2022; 71(6): 1117–26. https://doi.org/10.1136/gutjnl-2021-325214
59. Pasta A., Formisano E., Calabrese F., Plaz Torres M.C., Bodini G., Marabotto E., et al. Food intolerances, food allergies and IBS: Lights and Shadows. Nutrients. 2024; 16(2): 265. https://doi.org/10.3390/nu16020265
60. Khavkin A.I., Sitkin S.I. The effect of targeted probiotics on the microbiota – gut – immune system axis. Voprosy prakticheskoy pediatrii. 2023; 18(6): 107–18. https://doi.org/10.20953/1817-7646-2023-6-107-118 (in Russian)
61. Garzon Mora N., Jaramillo A.P. Effectiveness of probiotics in patients with constipation: a systematic review and meta-analysis. Cureus. 2024; 16(1): e52013. https://doi.org/10.7759/cureus.52013
62. Simon E., Călinoiu L.F., Mitrea L., Vodnar D.C. Probiotics, prebiotics, and synbiotics: implications and beneficial effects against irritable bowel syndrome. Nutrients. 2021; 13(6): 2112. https://doi.org/10.3390/nu13062112
63. Chlebicz-Wójcik A., Śliżewska K. Probiotics, prebiotics, and synbiotics in the irritable bowel syndrome treatment: A review. Biomolecules. 2021; 11(8): 1154. https://doi.org/10.3390/biom11081154
64. Shcherbakov P.L., Belova N.D., Generozov E.V., Zhgun E.S., Ivanova O.I., Ilyina E.N., et al. Faecal transplant in git treatment (pilot clinical experience). Doctor.Ru. 2019; (3): 40–6. https://doi.org/10.31550/1727-2378-2019-158-3-40-46 https://elibrary.ru/bsrtsj (in Russian)
65. Elhusein A.M., Fadlalmola H.A. Efficacy of fecal microbiota transplantation in irritable bowel syndrome patients: An updated systematic review and meta-analysis. Gastroenterol. Nurs. 2022; 45(1): 11–20. https://doi.org/10.1097/SGA.0000000000000652
66. El-Salhy M., Winkel R., Casen C., Hausken T., Gilja O.H., Hatlebakk J.G. Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome at 3 years after transplantation. Gastroenterology. 2022; 163(4): 982–94.e14. https://doi.org/10.1053/j.gastro.2022.06.020
67. Wang M., Xie X., Zhao S., Ma X., Wang Z., Zhang Y. Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Front. Immunol. 2023; 14: 1136343. https://doi.org/10.3389/fimmu.2023.1136343
68. Uwawah T.D., Nduma B.N., Nkeonye S., Kaur D., Ekhator C. A novel vibrating capsule treatment for constipation: A review of the literature. Cureus. 2024; 16(1): e52943. https://doi.org/10.7759/cureus.52943
Review
For citations:
Smirnova G.I., Labinov V.S., Korsunskiy A.A. Irritable bowel syndrome in children: pathogenetic significance of disorders of intestinal microbiota. Russian Pediatric Journal. 2024;27(1):49-54. (In Russ.) https://doi.org/10.46563/1560-9561-2024-27-1-49-54. EDN: xqpypx