Constipation is a common condition that may result from altered gastrointestinal motility. Several factors appear relevant to gut motility: the gut luminal environment (including the gastrointestinal microbiota and fermentation), as well as factors related to the immune system, the enteric nervous system, and the central nervous system.

Previous research has found associations between colonic transit time and aspects of patients’ gut microbiota in terms of composition, diversity, and also metabolic products. For instance, a longer colonic transit time was recently correlated with high microbial richness and with higher urinary levels of potentially harmful metabolites. In this line, a recent study, led by Dr. Jean-François Brugère from the Université d’Auvergne in France, explored the extent to which transit time could affect gut microbiota composition and metabolism, using a multi-compartmental in vitro continuous culture system simulating the physiological conditions of the proximal, transversal, and distal parts of the colon. The researchers found that an increase in transit time (96-hour transit time versus a normal 48 to 72-hour transit time) led to a decrease of both biomass and gut microbiota diversity in the transversal and distal compartments of the system.

Specifically, increased transit time led to the decrease of sulfate-reducing bacteria, major competitors of methanogenic archaea. The subsequent increased levels of methane could mediate slower transit time, as a previous study showed that methane slows intestinal transit and augments small intestinal contractile activity. Besides this, increased transit time resulted in increased carbohydrate fermentation in the proximal compartments, whereas there was an increase of putrefaction activity in the compartments simulating the transversal and distal colon. As this in vitro system allowed to study of the effect of transit time as a single variable, it can be concluded that colonic transit time, independently of other factors, may affect both the composition and metabolic activity of the gut microbiota.

There has been increasing evidence (here; here; here and here) investigating the role of gut microbiota and possible microbiota-based therapies on gut motility and constipation. According to a recent review, the most explored microbiota-based therapies for constipation include dietary fibres, prebiotics, probiotics and faecal microbiota transplantation:

  • Dietary fibres: fibres from plant foods (mainly vegetables, legumes, and fruits) can promote the excretion of bacterial fermentation products that can increase stool bulk and have pro-motility effects. Beyond a low-fibre diet, other factors may explain dysbiosis in chronic constipation. A recent observational study of 79 children aged 6 to 36 months (39 constipated children and 40 non-constipated children) found that constipated children had a smaller concentration of Lactobacilli in their stool than non-constipated children. Besides this, constipated children consumed more dairy products, were more frequently delivered via caesarean section, were weaned earlier and had a family history of constipation.
  • Prebiotics: randomized controlled trials assessing the effect of prebiotics for the management of chronic constipation in both animals and humans have reported contradictory results and, thus, the effectiveness of prebiotics in managing constipation in clinical practice remains unclear.
  • Probiotics: a recent systematic review and meta-analysis of 14 randomized controlled trials (n = 1182 participants) showed that administration of 108 to 3 x 1010 colony forming units (CFU)/day for 2 to 8 weeks of specific probiotic species and strains decreased gut transit time by 12 hours, increased stool frequency by 1.5 stools/week, and improved some constipation-related symptoms in adults with functional constipation. The probiotics were provided in yogurt, fermented milks, beverages, sachets, capsules, or probiotic-fortified foods. The effects of probiotics were species- and strain-specific, with different Bifidobacterium lactis strains improving gut transit time, stool frequency and consistency, and flatulence, whereas the strain Lactobacillus casei Shirota did not confer any beneficial results.

Chronic constipation is a common problem among elderly people and a recent systematic review of 4 randomised and placebo-controlled trials suggests that administration of probiotics could be an alternative to traditional drug  treatments in older individuals, as they significantly improved constipation by 10-40% compared to placebo controls without a probiotic. Studied probiotics included Bifidobacterium longum, B. lactis, and a mixture of Lactobacillus, Bifidobacterium and Streptococcus strains with doses from 109 to 4.5 x 1011 CFU/day for 6 to 25 weeks.

When considering constipation in adults with chronic disease, a recent randomized, double-blind, placebo-controlled trial found that the consumption of a fermented milk containing multiple probiotic strains and prebiotic fibre is superior to placebo in improving constipation in patients with Parkinson’s disease.

Among the mechanisms involved in the effect of probiotics on gut motility and constipation, a recent review has proposed: (1) modification of the altered intestinal microbiota in patients with constipation (“microbiota-dependent” effect); (2) modulation of gut sensation and motility function through probiotic metabolites; (3) modification of the intraluminal environment through increasing the end products of bacterial fermentation (e.g. saccharolytic bacteria, such as Bifidobacterium and Lactobacillus ferment fibres into short-chain fatty acids, which reduce intestinal pH and consequently increase intestinal motility), and (4) modulation of the mucosal immune barrier and/or systemic immune barrier and gut mucosal inflammation and altered sensory and motor functions. However, the contribution of each mechanism of probiotics on gut transit time and constipation is not fully understood and deserves further research.

  • Faecal microbiota transplantation (FMT): there are few published studies assessing the efficacy of FMT on constipation but it is too early to make clear conclusions for its clinical use in constipation.

On the whole, the altered gut microbiota may play a role in the pathogenesis of chronic constipation. Although the exact mechanisms are poorly understood, microbiota-based therapies –specifically probiotics– are emerging as a promising tool for the management of chronic constipation.


References:

Barichella M, Pacchetti C, Bolliri C, et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: an RCT. Neurology. 2016; 87(12):1274-80. doi: 10.1212/WNL.0000000000003127.

De Moraes JG, Motta ME, Beltrão MF, Salviano TL, da Silva GA. Fecal microbiota and diet of children with chronic constipation. Int J Pediatr. 2016:6787269. doi: 10.1155/2016/6787269.

Dimidi E, Christodoulides S, Scott SM, Whelan K. Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation. Adv Nutr. 2017; 8(3):484-94. doi: 10.3945/an.116.014407.

Dimidi E, Christodoulides S, Fragkos KC, Scott SM, Whelan K. The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014; 100(4):1075-84. doi: 10.3945/ajcn.114.089151.

Martínez-Martínez MI, Calabuig-Tolsá R, Cauli O. The effect of probiotics as a treatment for contipation in elderly people: a systematic review. Arch Gerontol Geriatr. 2017; 71:142-9. doi: 10.1016/j.archger.2017.04.004.

Tottey W, Feria-Gervasio D, Gaci N, et al. Colonic transit time is a driven force of the gut microbiota composition and metabolism: in vitro evidence. J Neurogastroenterol Motil. 2017; 23(1):124-34. doi: 10.5056/jnm16042.

Zhao Y, Yu YB. Intestinal microbiota and chronic constipation. Springerplus. 2016; 5(1):1130. doi: 10.1186/s40064-016-2821-1.