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Iancu, M.A.; Profir, M.; Roşu, O.A.; Ionescu, R.F.; Cretoiu, S.M.; Gaspar, B.S. The Role of Intestinal Microbiome in Constipation. Encyclopedia. Available online: https://encyclopedia.pub/entry/49518 (accessed on 16 November 2024).
Iancu MA, Profir M, Roşu OA, Ionescu RF, Cretoiu SM, Gaspar BS. The Role of Intestinal Microbiome in Constipation. Encyclopedia. Available at: https://encyclopedia.pub/entry/49518. Accessed November 16, 2024.
Iancu, Mihaela Adela, Monica Profir, Oana Alexandra Roşu, Ruxandra Florentina Ionescu, Sanda Maria Cretoiu, Bogdan Severus Gaspar. "The Role of Intestinal Microbiome in Constipation" Encyclopedia, https://encyclopedia.pub/entry/49518 (accessed November 16, 2024).
Iancu, M.A., Profir, M., Roşu, O.A., Ionescu, R.F., Cretoiu, S.M., & Gaspar, B.S. (2023, September 22). The Role of Intestinal Microbiome in Constipation. In Encyclopedia. https://encyclopedia.pub/entry/49518
Iancu, Mihaela Adela, et al. "The Role of Intestinal Microbiome in Constipation." Encyclopedia. Web. 22 September, 2023.
The Role of Intestinal Microbiome in Constipation
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This entry is adapted from the peer-reviewed paper 10.3390/microorganisms11092177

The gut microbiota represents a community of microorganisms (bacteria, fungi, archaea, viruses, and protozoa) that colonize the gut and are responsible for gut mucosal structural integrity and immune and metabolic homeostasis. The relationship between the gut microbiome and human health has been intensively researched in the past years. The gut microbial population plays a key role in intestinal motility, and dysbiosis has been correlated with chronic constipation.

microbiota microbiome diarrhea constipation probiotic

1. Introduction

Gastrointestinal conditions like diarrhea and constipation represent common health problems around the world. Studies show that both diarrhea and constipation are associated with changes that appear in the gut microbial composition [1][2]. Two interchangeable terms are used in the literature: “microbiota” and “microbiome”. Between the two there are subtle differences, because “microbiota” refers to the entire collection of microbial communities found in a specific habitat (e.g., oral cavity, skin, and intestine), while “microbiome” refers to the entire habitat, including the microbial communities, their genomes, metabolites, and the habitat-specific environmental conditions [3][4][5]. The human gut microbiota is a large micro ecosystem containing millions of microorganisms, including bacteria, fungi, and viruses, in perfect equilibrium with the host [6]. Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobiota are the dominant phyla of the gut microbiota, and 90% of the gut microbial composition is represented by the Firmicutes and Bacteroidetes phyla [7]. In addition to these microbial communities, the intestinal microbiome also includes the totality of genes present in the environment, plus the pathogens [8][9]. The gut microbiota is subjected to diverse influences like host genetics, age, environment, diet and lifestyle, medication usage, etc. [10][11].
Human health is significantly affected by the “core microbiome” alteration [12]. This core microbiome containing specific taxa common to the majority, if not all humans, is very important for host biological functions such as the fermentation of food, resistance to colonization and protection against pathogens, the stimulation of immune response, and metabolite and vitamin production [13]. Microbial balance (eubyosis) is also of major significance in maintaining the integrity of the intestinal barrier [14].
Any disturbance in the composition of the gut microbiota is regarded as dysbiosis and is associated with increased chances of disease occurrence [15]. Dysbiosis can occur due to several exogenous and endogenous factors like excessive/restrictive diet, medication, and immune system and intestinal mucosa integrity [16][17]. Depending on the severity of the dysbiosis, patients can experience a diverse palette of symptoms, from mild effects like cramps, diarrhea, and constipation to more serious chronic conditions [18][19]. Other common symptoms include chronic fatigue; acid reflux and/or heartburn; food intolerance, gas, and bloating; acne, skin rashes, and even psoriasis; inflammation and aching joints; vaginal or rectal infections or itching; attention deficit hyperactivity disorder (ADHD) or issues with concentration; and anxiety or depression [20][21][22]. Dysbiosis has been correlated with a number of conditions like autism, allergic disorders, inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), acute and chronic pancreatitis, and even colorectal cancer [23][24]. Moreover, dysbiosis has been linked to cardiovascular diseases and metabolic disorders such as obesity and type 1 diabetes mellitus [23][25][26][27].

2. Constipation

Chronic constipation is one of the conditions most frequently encountered by gastroenterologists, and it is associated with a negative impact on quality of life [28]. Between 15% and 20% of adults are affected by chronic constipation, and up to 33% of adults over 60 years old experience it [29]. Functional constipation affects children and adults, with important pathophysiological differences between the two groups [30]. A normal whole-intestinal transit time is 30 to 40 h [31]. Chronic constipation is most frequently idiopathic, but there are cases where it can be secondary to ongoing medication or diseases [32]. Diet, intestinal motility and absorption, anorectal motor and sensory function, behavioral factors, and psychological issues are all part of the pathophysiology of functional constipation [32]. Functional constipation is categorized into constipation with normal transit, slow-transit constipation. and rectal evacuation disorders [30]. Treating chronic constipation can be challenging, and current treatment strategies include dietary changes, treatment of depression, and the ingestion of bulking agents such as psyllium or methylcellulose, stimulating laxative medication, lactulose, and sorbitol [33]. Treatment options for chronic constipation may follow the recent American Gastroenterological Association/ American College of Gastroenterology (AGA/ACG) clinical practice guideline [34].
The enteric nervous system (ENS), the central nervous system (CNS), the immune system, and the intestinal luminal environment are the inter-related factors that control gastrointestinal motility [35]. Constipation symptoms might appear if perturbations occur in any of these systems [35]. The existence of a bidirectional “microbiota-gut-brain axis” [36] and its important role in regulating intestinal motility is supported by growing evidence [35][37]. Some studies have demonstrated that probiotics can positively affect gut motility by modulating the ENS or the CNS [38][39]. Some studies indicate that probiotics can increase gut motility by modifying the microbiota composition and microbial fermentation, which triggers the release of metabolites such as short-chain fatty acids, peptides, and lactic acid that interact with the ENS [35][40][41].
The gut microbial population plays a key role in intestinal motility, and dysbiosis has been correlated with chronic constipation [1]. Studies that have analyzed the microbiota in constipation and constipation-predominant irritable bowel syndrome have shown that there is a decrease in Bacteroides, Bifidobacterium, and Lactobacillus spp. Compared to control groups and an increase in potentially pathogenic bacteria such as Pseudomonas aeruginosa and Campylobacter jejuni [35][42][43][44][45]. A cross-sectional pilot study using 16S rRNA gene pyrosequencing reported that the microbiota of constipated patients presents a decreased concentration of Prevotella and increased concentrations of the Firmicutes genera [46]. Parthasarathy et al. also demonstrated the correlation between a more rapid transit time and increased concentrations of Actinobacteria, Bacteroides, and Lactococcus [44].
According to Barbara et al., the intestinal microbiota influences gut motility by releasing bacterial fermentation end-products via intestinal neuroendocrine factors and through mediators released by the gut immune response [47]. SCFAs, products of bacterial anaerobic metabolism, have been demonstrated to stimulate ileal propulsive contractions and appear to be able to directly stimulate ileal and colonic smooth-muscle contractility [45]. Moreover, SCFAs, especially butyrate, exhibit pro-absorptive NaCl and anti-secretory effects toward Cl− secretion [48].

Microbiota-Based Therapy of Constipation

Dietary fiber has been intensively recommended for treating chronic constipation due to its multiple benefits to intestinal microbiome health. Dietary fibers are known to increase the volume of the stool and soften it, as well as decrease transit time [49]. Dietary fiber acts as a substrate for microbial intestinal fermentation, stimulates the growth of beneficial bacteria, and promotes the excretion of fermentation end-products such as SCFAs, which adversely affect human health when built up [50]. Moreover, it was shown that dietary fiber can stimulate the growth of beneficial bacteria while suppressing pathogenic bacteria [51].
The low-FODMAP diet shows good results in patients with constipation-predominant IBS (IBS-C). However, it also decreases fiber intake, thus leading to aggravating constipation in some cases of IBS-C [52]. Although there is still insufficient evidence to demonstrate the beneficial effect of nutritional approaches on gut microbiota manipulation for the overall improvement of different chronic digestive diseases, diet modifications seem helpful for symptom alleviation [53][54][55].
Prebiotics are non-digestible carbohydrates that promote the health of the host by stimulating the growth of some commensal gut bacteria, such as Lactobacilli and Bifidobacteria [56]. Prebiotics like inulin, fructo-oligosaccharides, and galacto-oligosaccharides are metabolized in the intestinal lumen and transformed into lactic acid and short-chain carboxylic acid [45]. Studies on mice have demonstrated that prebiotic oligosaccharides stimulate gut peristalsis, thus alleviating constipation symptoms [57]. In the clinical setting, lactulose relieves constipation and increases fecal Bifidobacteria counts [58]. In the clinical setting, no significant differences were observed in the relief of constipation when compared to placebo [58][59].
Probiotics are extensively used as alternative treatment options in patients suffering from constipation due to their beneficial effects [60]. Probiotics may benefit patients suffering from chronic constipation by modifying the intestinal luminal environment and changing the composition of altered gut microbiota [61][62]. The consumption of B. lactis containing fermented milk increased stool frequency and improved stool consistency and defecation conditions in a population of Chinese women suffering from constipation [63]. In addition, one systematic review demonstrated that B. lactis reduced whole-gut transit time, increased stool frequency, and improved stool consistency in patients with functional constipation [35]. One of the most recent trials evaluated the clinical efficacy of multiple strains of probiotics in treating chronic constipation in elderly patients using a multi-probiotic mixture containing Bifidobacterium animalis subsp. lactis BCL1, L. acidophilus LA3, and L. casei BGP93 [64]. After 71 days, the cumulative stool number was significantly higher in the probiotic group compared to placebo [64]. Recently, a meta-analysis by Zhang et al. identified 15 randomized controlled trials (RCTs) that investigated the efficacy of probiotic administration in constipation. Gut transit time (GTT), stool frequency, consistency, and bloating were analyzed. The meta-analysis demonstrated that probiotics such as Bifidobacterium, Lactobacillus, and Streptococcus ameliorate functional constipation by increasing stool frequency and decreasing gut transit time and stool consistency. However, symptoms of bloating were not significantly reduced [65]. Compared to single-species probiotics, multispecies probiotics were found to significantly improve symptoms of constipation [64]. The superior results obtained with multispecies probiotic administration may be explained by synergistic interactions between probiotic strains [64][66]. One systematic review of nine RCTs that investigated the clinical efficacy of probiotics in treating constipation in elderly people reported that probiotic therapy significantly improved constipation compared to placebo groups, with B. longum being the most frequently tested probiotic among the analyzed trials [67].
Synbiotics represent a mixture of probiotics and prebiotics. One randomized controlled study evaluated the efficacy of a synbiotic combination containing Bifidobacterium longum (B. longum) NCIMB 30182, Bifidobacterium breve (B. breve) NCIMB 30180, Lactobacillus casei (L. casei) NCIMB1 30185, Lactobacillus rhamnosus (L. rhamnosus) NCIMB 30188, L. acidophilus NCIMB 30184, Lactobacillus bulgaricus (L. bulgaricus) NCIMB 30186, Streptococcus thermophilus (S. thermophilus) NCIMB 30189, and fructo-oligosaccharides in ameliorating constipation in a population of 66 men with chronic idiopathic constipation [68]. A second RCT used a synbiotic combination of B. lactis HN019, Lactobacillus paracasei (L. paracasei) Lpc-37, L. rhamnosus HN001, and L. acidophilus (NCFM), fructo-oligosaccharides in a population of women suffering from chronic idiopathic constipation [69]. In addition, studies have demonstrated the efficiency of synbiotics in ameliorating constipation in children with chronic constipation [70][71].
The agents mentioned above are generally well tolerated, and their administration is considered safe. Probiotics, prebiotics, and synbiotics may represent an effective treatment option for patients suffering from chronic constipation. However, further studies are needed to evaluate specific species strains and the optimal treatment dosages and durations.
In patients with chronic constipation, Zhang et al. demonstrated that FMT in combination with soluble dietary fiber had both short-term and long-term efficacy in treating slow-transit constipation [72]. In an early study by Borody et al., FMT demonstrated significant improvement in defecation frequency and symptoms like abdominal pain, early satiety, and nausea [73]. A significant increase in defecation frequency and stool consistency was also demonstrated by Ge et al. in a case series that investigated FMT in six patients with slow-transit constipation [74]. In one RCT, 60 adult patients with slow-transit-time constipation were randomized to receive either FMT or conventional treatment. The FMT group had significantly improved constipation symptoms, demonstrating that FMT effectively treated constipation [75].
FMT was proven effective in treating both refractory diarrhea and refractory constipation. However, this procedure is associated with high risks, and the Food and Drug Administration has issued a warning following the death of one patient after FMT and after one patient developed an infection [76]. Moreover, immunocompromised patients are at risk of developing bloodstream infections if undergoing FMT [77]. Due to the dangers associated with FMT, the challenge in identifying donors, and the complexity of the procedure, only selected cases of patients who are refractory to conventional treatment options should undergo this procedure.

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Subjects: Integrative & Complementary Medicine
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Mihaela Adela Iancu
,
Monica Profir
,
Oana Alexandra Roşu
,
Ruxandra Florentina Ionescu
,
Sanda Maria Cretoiu
,
Bogdan Severus Gaspar
View Times: 392
Entry Collection: Gastrointestinal Disease
Revision: 1 time (View History)
Update Date: 22 Sep 2023
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