Gut Microbiota and Chronic Constipation: A Review and Update

Toshifumi Ohkusa, Shigeo Koido, Yuriko Nishikawa, Nobuhiro Sato, Toshifumi Ohkusa, Shigeo Koido, Yuriko Nishikawa, Nobuhiro Sato

Abstract

Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: "IBS," "IBS-C," "irritable bowel syndrome," "irritable bowel syndrome with constipation," "functional constipation," "chronic constipation" in combination with "gut microbiota," "dysbiosis," "gut microflora" for microbiota in chronic constipation, and in combination with "probiotics," "prebiotics," "synbiotics," "antibiotics," and "fecal microbiota transplantation." Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.

Keywords: FMT; antibiotics; chronic constipation; functional constipation; gut microbiota; irritable bowel syndrome with constipation; probiotics; synbiotics.

Figures

Figure 1
Figure 1
Three broad categories of functional constipation.
Figure 2
Figure 2
Dysbiosis in IBS-C patient.

References

    1. Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. (2016) 375:2369–79. 10.1056/NEJMra1600266
    1. Yusof N, Hamid N, Ma ZF, Lawenko RM, Wan Mohammad WMZ, Collins DA, et al. . Exposure to environmental microbiota explains persistent abdominal pain and irritable bowel syndrome after a major flood. Gut Pathog. (2017) 9:75. 10.1186/s13099-017-0224-7
    1. Simrén M, Barbara G, Flint HJ, Spiegel BM, Spiller RC, Vanner S, et al. . Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut (2013) 62:159–76. 10.1136/gutjnl-2012-302167
    1. Zoppi G, Cinquetti M, Luciano A, Benini A, Muner A, Bertazzoni Minelli E. The intestinal ecosystem in chronic functional constipation. Acta Paediatr. (1998) 87:836–41. 10.1111/j.1651-2227.1998.tb01547.x
    1. Khalif IL, Quigley EM, Konovitch EA, Maximova ID. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Dig Liver Dis. (2005) 37:838–49. 10.1016/j.dld.2005.06.008
    1. Zhu L, Liu W, Alkhouri R, Baker RD, Bard JE, Quigley EM, et al. . Structural changes in the gut microbiome of constipated patients. Physiol Genomics (2014) 46:679–86. 10.1152/physiolgenomics.00082.2014
    1. Kim SE, Choi SC, Park KS, Park MI, Shin JE, Lee TH, et al. Change of fecal flora and effectiveness of the short-term VSL#3 Probiotic treatment in patients with functional constipation. J Neurogastroenterol Motil. (2015) 21:111–20. 10.5056/jnm14048
    1. Parthasarathy G, Chen J, Chen X, Chia N, O'Connor HM, Wolf PG, et al. . Relationship between microbiota of the Colonic Mucosa vs feces and symptoms, colonic transit, and methane production in female patients with chronic constipation. Gastroenterology (2016) 150:367–79. 10.1053/j.gastro.2015.10.005
    1. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. . Human gut microbiome viewed across age and geography. Nature (2012) 486:222–7. 10.1038/nature11053
    1. Malinen E, Rinttilä T, Kajander K, Mättö J, Kassinen A, Krogius L, et al. . Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am J Gastroenterol. (2005) 100:373–82. 10.1111/j.1572-0241.2005.40312.x
    1. Maukonen J, Satokari R, Mättö J, Söderlund H, Mattila-Sandholm T, Saarela M. Prevalence and temporal stability of selected clostridial groups in irritable bowel syndrome in relation to predominant faecal bacteria. J Med Microbiol. (2006) 55:625–33. 10.1099/jmm.0.46134-0
    1. Rajilić-Stojanović M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, et al. . Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology (2011) 141:1792–801. 10.1053/j.gastro.2011.07.043
    1. Chassard C, Dapoigny M, Scott KP, Crouzet L, Del'homme C, Marquet P, et al. . Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther. (2012) 35:828–38. 10.1111/j.1365-2036.2012.05007.x
    1. Durbán A, Abellán JJ, Jiménez-Hernández N, Salgado P, Ponce M, Ponce J, et al. . Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome. Environ Microbiol Rep. (2012) 4:242–7. 10.1111/j.1758-2229.2012.00327.x
    1. Parkes GC, Rayment NB, Hudspith BN, Petrovska L, Lomer MC, Brostoff J, et al. . Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome. Neurogastroenterol Motil. (2012) 24:31–9. 10.1111/j.1365-2982.2011.01803.x
    1. Bouhnik Y, Neut C, Raskine L, Michel C, Riottot M, Andrieux C, et al. . Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation. Aliment Pharmacol Ther. (2004) 19:889–99. 10.1111/j.1365-2036.2004.01918.x
    1. Linetzky Waitzberg D, Alves Pereira CC, Logullo L, Manzoni Jacintho T, Almeida D, Teixeira da Silva ML, et al. . Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women. Nutr Hosp. (2012) 27:123–9. 10.1590/S0212-16112012000100014
    1. Koebnick C, Wagner I, Leitzmann P, Stern U, Zunft HJ. Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation. Can J Gastroenterol. (2003) 17:655–9. 10.1155/2003/654907
    1. Yang YX, He M, Hu G, Wei J, Pages P, Yang XH, et al. . Effect of a fermented milk containing Bifidobacterium lactis DN-173010 on Chinese constipated women. World J Gastroenterol. (2008) 14:6237–43. 10.3748/wjg.14.6237
    1. Waller PA, Gopal PK, Leyer GJ, Ouwehand AC, Reifer C, Stewart ME, et al. . Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time and functional gastrointestinal symptoms in adults. Scand J Gastroenterol. (2011) 46:1057–64. 10.3109/00365521.2011.584895
    1. Ishizuka A, Tomizuka K, Aoki R, Nishijima T, Saito Y, Inoue R, et al. . Effects of administration of Bifidobacterium animalis subsp. lactis GCL2505 on defecation frequency and bifidobacterial microbiota composition in humans. J Biosci Bioeng. (2012) 113:587–91. 10.1016/j.jbiosc.2011.12.016
    1. Riezzo G, Orlando A, D'Attoma B, Guerra V, Valerio F, Lavermicocca P, et al. Randomised clinical trial: efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation–a double-blind, controlled, crossover study. Aliment Pharmacol Ther. (2012) 35:441–50. 10.1111/j.1365-2036.2011.04970.x
    1. Favretto DC, Pontin B, Moreira TR. Effect of the consumption of a cheese enriched with probiotic organisms (Bifidobacterium lactis bi-07) in improving symptoms of constipation. Arq Gastroenterol. (2013) 50:196–201. 10.1590/S0004-28032013000200035
    1. Mazlyn MM, Nagarajah LH, Fatimah A, Norimah AK, Goh KL. Effects of a probiotic fermented milk on functional constipation: a randomized, double-blind, placebo-controlled study. J Gastroenterol Hepatol. (2013) 28:1141–7. 10.1111/jgh.12168
    1. Mezzasalma V, Manfrini E, Ferri E, Sandionigi A, La Ferla B, Schiano I, et al. . A randomized, double-blind, placebo-controlled trial: the efficacy of multispecies probiotic supplementation in alleviating symptoms of irritable bowel syndrome associated with constipation. Biomed Res Int. (2016) 2016:4740907. 10.1155/2016/4740907
    1. Yoon JY, Cha JM, Oh JK, Tan PL, Kim SH, Kwak MS, et al. . Probiotics ameliorate stool consistency in patients with chronic constipation: a randomized, double-blind, placebo-controlled study. Dig Dis Sci. (2018) 63:2754–64. 10.1007/s10620-018-5139-8
    1. Bu LN, Chang MH, Ni YH, Chen HL, Cheng CC. Lactobacillus casei rhamnosus Lcr35 in children with chronic constipation. Pediatr Int. (2007) 49:485–90. 10.1111/j.1442-200X.2007.02397.x
    1. Coccorullo P, Strisciuglio C, Martinelli M, Miele E, Greco L, Staiano A. Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a double-blind, randomized, placebo-controlled study. J Pediatr. (2010) 157:598–602. 10.1016/j.jpeds.2010.04.066
    1. Guerra PV, Lima LN, Souza TC, Mazochi V, Penna FJ, Silva AM, et al. . Pediatric functional constipation treatment with Bifidobacterium-containing yogurt: a crossover, double-blind, controlled trial. World J Gastroenterol. (2011) 17:3916–21. 10.3748/wjg.v17.i34.3916
    1. Tabbers MM, Chmielewska A, Roseboom MG, Crastes N, Perrin C, Reitsma JB, et al. . Fermented milk containing Bifidobacterium lactis DN-173 010 in childhood constipation: a randomized, double-blind, controlled trial. Pediatrics (2011) 127:e1392–9. 10.1542/peds.2010-2590
    1. Wojtyniak K, Horvath A, Dziechciarz P, Szajewska H. Lactobacillus casei rhamnosus Lcr35 in the management of functional constipation in children: a randomized trial. J Pediatr. (2017) 184:101–5. 10.1016/j.jpeds.2017.01.068
    1. Banaszkiewicz A, Szajewska H. Ineffectiveness of Lactobacillus GG as an adjunct to lactulose for the treatment of constipation in children: a double-blind, placebo-controlled randomized trial. J Pediatr. (2005) 146:364–9. 10.1016/j.jpeds.2004.10.022
    1. Khodadad A, Sabbaghian M. Role of synbiotics in the treatment of childhood constipation: a double-blind randomized placebo controlled trial. Iran J Pediatr. (2010) 20:387–92.
    1. Saneian H, Tavakkol K, Adhamian P, Gholamrezaei A. Comparison of Lactobacillus sporogenes plus mineral oil and mineral oil alone in the treatment of childhood functional constipation. J Res Med Sci. (2013) 18:85–8.
    1. Sadeghzadeh M, Rabieefar A, Khoshnevisasl P, Mousavinasab N, Eftekhari K. The effect of probiotics on childhood constipation: a randomized controlled double-blind clinical trial. Int J Pediatr. (2014) 2014:937212. 10.1155/2014/937212
    1. Bazzocchi G, Giovannini T, Giussani C, Brigidi P, Turroni S. Effect of a new synbiotic supplement on symptoms, stool consistency, intestinal transit time and gut microbiota in patients with severe functional constipation: a pilot randomized double-blind, controlled trial. Tech Coloproctol. (2014) 18:945–53. 10.1007/s10151-014-1201-5
    1. Lim YJ, Jamaluddin R, Hazizi AS, Chieng JY. Effects of synbiotics among constipated adults in serdang, selangor, malaysia-a randomised, double-blind, placebo-controlled trial. Nutrients (2018) 10:824. 10.3390/nu10070824
    1. Sahakian AB, Jee SR, Pimentel M. Methane and the gastrointestinal tract. Dig Dis Sci. (2010) 55:2135–43. 10.1007/s10620-009-1012-0
    1. Lee KM, Paik CN, Chung WC, Yang JM, Choi MG. Breath methane positivity is more common and higher in patients with objectively proven delayed transit constipation. Eur J Gastroenterol Hepatol. (2013) 25:726–32. 10.1097/MEG.0b013e32835eb916
    1. Attaluri A, Jackson M, Valestin J, Rao SS. Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBS. Am J Gastroenterol. (2010) 105:1407–11. 10.1038/ajg.2009.655
    1. Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaximin and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test. J Clin Gastroenterol. (2010) 44:547–50. 10.1097/MCG.0b013e3181c64c90
    1. Borody TJ, George L, Andrews P, Brandl S, Noonan S, Cole P, et al. . Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Med J Aust. (1989) 150:604.
    1. Andrews PJ, Barnes P, Borody TJ Chronic constipation reversed by restoration of bowel flora. A case and a hypothesis. Eur J Gastroenterol Hepatol. (1992) 4:245–7.
    1. Ge X, Zhao W, Ding C, Tian H, Xu L, Wang H, et al. . Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility. Sci Rep. (2017) 7:441. 10.1038/s41598-017-00612-y
    1. Tian H, Ge X, Nie Y, Yang L, Ding C, McFarland LV, et al. . Fecal microbiota transplantation in patients with slow-transit constipation: a randomized, clinical trial. PLoS ONE (2017) 12:e0171308. 10.1371/journal.pone.0171308
    1. Ding C, Fan W, Gu L, Tian H, Ge X, Gong J, et al. . Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up. Gastroenterol Rep. (2018) 6:101–7. 10.1093/gastro/gox036
    1. Zhang X, Tian H, Gu L, Nie Y, Ding C, Ge X, et al. . Long-term follow-up of the effects of fecal microbiota transplantation in combination with soluble dietary fiber as a therapeutic regimen in slow transit constipation. Sci China Life Sci. (2018) 61:779–86. 10.1007/s11427-017-9229-1

Source: PubMed

3
Prenumerera