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The Significance of the Gut Microbiome in Children with Functional Constipation

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The Significance of the Gut Microbiome in Children with Functional Constipation Reviews The significance of the gut microbiome in children with functional constipation Monika KwiatkowskaA–F, Aneta KrogulskaA–F Department of Pediatrics, Allergology and Gastroenterology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland A – research concept and design; B – collection and/or assembly of data; C – data analysis and interpretation; D – writing the article; E – critical revision of the article; F – final approval of the article Advances in Clinical and Experimental Medicine, ISSN 1899–5276 (print), ISSN 2451–2680 (online) Adv Clin Exp Med. 2021;30(4):471–480 Address for correspondence Abstract Monika Kwiatkowska E-mail: [email protected] Constipation is a widespread problem in pediatric practice, affecting almost 30% of pediatric population. As much as 90–95% of constipation cases have a functional basis, and although the pathogenesis of func- Funding sources None declared tional constipation remains unclear, its etiology is considered to be multifactorial. Its growing prevalence has been attributed to the occurrence of disorders in the homeostasis of gastrointestinal microbiota. In humans, Conflict of interest the best known microbiome is that of the intestines, which has been the subject of a number of studies None declared based on recognition of the 16S rRNA gene sequence. Microbiota are believed to influence the pathogenesis of functional constipation by affecting peristalsis, relationship with diet, and physical activity. The paper evaluates the role of intestinal microbiota in functional constipation and describes its contribution to the onset Received on July 28, 2020 of disease. Determining the importance of the microbiome in the pathogenesis of functional constipation Reviewed on October 12, 2020 Accepted on December 6, 2020 creates hope for the development of new prevention and treatment methods. Published online on April 28, 2021 Key words: microbiota, 16S rRNA, peristalsis, childhood Cite as Kwiatkowska M, Krogulska A. The significance of the gut microbiome in children with functional constipation. Adv Clin Exp Med. 2021;30(4):471–480. doi:10.17219/acem/131215 DOI 10.17219/acem/131215 Copyright © 2021 by Wroclaw Medical University This is an article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/) 472 M. Kwiatkowska, A. Krogulska. The gut microbiome and FC Introduction Table 2. Differential diagnosis of constipation according to age in children12 Children older Constipation is a troublesome condition characterized Cause of constipation Infants than 1 year by the production of hard, compact stool which requires rare (prevalence more than 95% of cases Functional constipation great effort to pass. Consequently, stool is passed less fre- 3–12.1%) (prevalence 0.5–32.2%) quently than would be typical for a given age. The norms Hirschsprung’s disease yes yes of defecation frequency depending on age are presented Congenital anorectal in Table 1.1 Constipation is one of the most common yes rarely malformations childhood complaints, being reported by up to 29.6% Neurological disorders yes rarely of the population of pediatric population.2–4 It is slightly more common in boys than in girls.5 The condition ac- Encephalopathy yes rarely counts for 3–5% of visits to pediatricians and 10–25% Spinal cord abnormalities: 3,6 myelo meningocele, spina yes rarely of visits to pediatric gastroenterologists. In addi- bifida, tethered cord tion to its widespread prevalence, constipation is also Cystic fibrosis yes yes becoming more common; this rise has been attrib- Metabolic causes: uted to a range of causes, such as poor diet, reduced hypothyroidism, hyper- yes yes physical activity, rapidly progressing socio-cultural calcemia, hypokalemia, changes, increasing stress levels, and inappropriate pa- diabetes insipidus rental attitude.7,8 In as many as a quarter of children, Heavy metal poisoning yes yes 9 the problem of constipation persists into adulthood. Medication side effects yes yes In addition, it is a clinical problem that generates high Gluten enteropathy no yes costs for healthcare: the number of children hospital- Spinal cord trauma no yes ized due to constipation in the USA increased by 112% Neurofibromatosis rarely yes in the period 1997–2009, and the costs associated with Developmental delay rarely yes hospitalization increased by 221.5%.7 The importance of constipation is demonstrated by its significant im- Sexual abuse rarely yes pact on the quality of life of both children and their families.3,7 prevalence reported in toddlers.11 The differential di- Table 1. Normal frequency of bowel movements in infants and children1 agnosis of constipation depending on age is presented 12 Mean number of bowel Mean number of bowel in Table 2. The bases for recognizing functional con- Age movements per week movements per day stipation according to the Rome IV criteria are presented 0–3 months in Table 3.13,14 5–40 2.9 (breastfed) 0–3 months 5–28 2.0 (formula-fed) Etiology of functional constipation 6–12 months 5–28 1.8 1–3 years 4–21 1.4 Although the etiology of functional constipation is be- Over 3 years 3–14 1.0 lieved to be multifactorial, it remains poorly under- stood.7,15–17 The basic causative factor is believed to be conscious stopping of defecation due to pain or fear, thus Constipation can cause a number of symptoms, such resulting in a “vicious circle”.15 Such withholding of stool as abdominal pain, bloating, painful bowel movements, is believed to be the cause of constipation in 50% of younger lack of appetite, fecal staining of underwear, vomiting, children.7 The prolonged stasis and accumulation of fecal and even intestinal obstruction and perforation.3,8 In ad- mass leads to an enlargement of the rectum and a decrease dition, children with constipation are more likely to suffer in anal muscle contraction efficiency, resulting in pelvic from urinary tract infections and bedwetting,10 and this floor muscle fatigue, weakness of anal sphincter function cohort demonstrates an increased risk of various emo- and fecal incontinence.7,16 Almost 30% of children with tional disorders, such as anxiety and irritability.8 When left functional constipation soil their underwear.17 untreated, or inadequately treated, long-term constipation Functional constipation is typically categorized into nor- can adversely affect child’s development. mal transit constipation (NTC), slow transit constipation It is believed that 5% of cases of constipation may be (STC), and defecatory or rectal evacuation disorders. Def- organic in origin, while the other 95% are functional. ecatory or rectal evacuation disorders are caused by pelvic Prevalence rates for functional constipation in children floor dyssynergia (PFD) as well as a reduction in intra- aged 0–18 years range from 0.5% to 32.2%.11 The preva- abdominal pressure, rectal sensory perception and rectal lence varies according to age groups, with the highest contraction.18 Adv Clin Exp Med. 2021;30(4):471–480 473 Table 3. Rome IV criteria for functional constipation13,14 Criteria Children <4 years * Children >4 years ** • 2 or fewer defecations per week • 2 or fewer defecations in the toilet per week • history of excessive stool retention • at least 1 episode of fecal incontinence per week • history of painful or hard bowel movements • history of retentive posturing or excessive volitional stool retention • history of large-diameter stools • history of painful or hard bowel movements Rome IV • presence of a large fecal mass in the rectum • presence of a large fecal mass in the rectum criteria In toilet-trained children, the following additional criteria may be • history of large-diameter stools that can obstruct the toilet used: • at least 1 episode/week of incontinence after the acquisition of toileting skills • history of large-diameter stools that may obstruct the toilet * Must fulfill ≥2 criteria at least once per week for a minimum of 1 month with insufficient criteria for a diagnosis of irritable bowel syndrome. ** Must fulfill ≥2 criteria at least once per week for a minimum of 1 month with insufficient criteria for a diagnosis of irritable bowel syndrome. After appropriate evaluation, the symptoms cannot be fully explained by another medical condition. Rao et al. showed that dyssynergic defecation was de- related to physical activity and diet, is commonly asso- tected in 27–59% of patients, slow colonic transit in 3–47%, ciated with a higher risk of constipation,27 although no and an overlap of dyssynergic defecation and slow colonic such relationship has been confirmed.28 Other lifestyle transit or constipation-predominant irritable bowel syn- factors that increase the risk of constipation include poor drome (IBS-C) was commonly present.19 Dyssynergic def- socioeconomic conditions and low maternal education.4 ecation is common and affects up to ½ of patients with Stress has also been found to be associated with constipa- chronic constipation.19 The PFD prevalence varies between tion in children,29 which can lead to permanent changes 11% and 74%; it is typically present in about 50% of patients. in gastrointestinal motility, visceral sensitivity and hypo- The exact prevalence of PFD in children is unknown. thalamic–pituitary–adrenal dysfunction.7,26 In addition, According to Whitehead et al., PFD is found in 25–50% constipation has been found to be more common in chil- of both children and adults.20 Another study showed slow dren who receive less attention from parents, and who may transit constipation in 60% of the children with constipa- get insufficient sleep.29 tion, and among them, 13% had pelvic floor dysfunction.21 In addition to environmental factors, genetic factors Zar-Kessler at al. completed a retrospective chart review may also be important in the development of constipa- over 15 months of patients aged 5–18 years with chronic tion, since it has been shown that a positive family history constipation.
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