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Gastroenterology & Hepatology
Irritable bowel syndrome (IBS) is a relatively common digestive disorder. It is estimated that IBS has a prevalence of 10–15% in the general population in industrialized countries and is a factor with a significant impact on both the individual and society in terms of quality of life and health care costs. Depending on symptomatology, comorbidities, quality of life and healthcare needs, IBS can have a mild, moderate, or severe clinical course. Some studies have shown that the severe form occurs in 15–40% of patients with IBS.
- irritable bowel syndrome
- gut–brain axis
- gut microbiota
- inflammation
1. Role of Probiotics in IBS Pathogenesis and Management
Experimental and clinical studies carried out in the last decades have suggested several mechanisms by which probiotics favourably modulate the pathophysiological mechanisms involved in IBS. Table 1 presents the bacterial strains commonly used in probiotics.
Table 1. The most important organisms used as probiotics in clinical practice.
| Genus | Lactobacillus | Bifidobacterium | Other |
|---|---|---|---|
| Species | Lactobacillus acidophilus | Bifidobacterium animalis spp. Lactis | Bacillus coagulans |
| Lactobacillus casei | Bifidobacterium breve | Enterococcus faecalis | |
| Lactobacillus helveticus | Bifidobacterium infantis spp. Lactis | Saccharomyces boulardii | |
| Lactobacillus johnsonii | Bifidobacterium longum | Streptococcus thermophilus | |
| Lactobacillus paracasei | |||
| Lactobacillus plantarum | |||
| Lactobacillus reuteri | |||
| Lactobacillus rhamnosus |
Probiotics serve a key role in improving IBS symptoms, including flatulence, abdominal pain, and bloating [82]. Probiotics mainly influence the composition of the microbiota, improving intestinal motility, VH, immune function, and metabolic processes, with a beneficial effect on dysfunctions of the microbiota-GBA and psychiatric conditions. The main benefits discussed in the literature are presented in Table 2.
Table 2. Benefits observed with the use of probiotics in irritable bowel syndrome.
| Benefit | Probiotics | References |
|---|---|---|
| Pathogenic microbiota development inhibition | Bifidobacterium spp., Lactobacillus spp. | [83,84] |
| Intestinal motility improvement | Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium longum, Bacillus subtilis, Streptococcus faecium, Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus | [85,86,87,88,89] |
| Antinociception | Bifidobacterium lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, Lactococcus lactis | [90,91] |
| Decrease in inflammatory and immune response | Bifidobacterium infantis, Lactobacillus lactis, Lactobacillus acidophilus, E. coli Nissle | [92,93] |
| Stress response improvement | Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Streptococcus casei, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus bulgaricus | [94,95] |
1.1. Role of Probiotics in the Restoration of Microbiota Composition
By increasing in Lactobacilli and Bifidobacteria, probiotics participate in restoring and stabilizing an unfavourable intestinal ecosystem for pathogenic bacteria, both by metabolites (lactic acid, short-chain fatty acids, hydrogen peroxide) and by bacteriocins (lactocin, acidophilin, bifidin, bifidocin) [83].
The competition for nutrients inhibits the development of pathogen microbes, particularly certain species of Clostridium, Escherichia coli, Salmonella, Shigella, and Pseudomonas. There are studies that have shown that probiotics stimulate the local production of mucins, thus decreasing adhesion of pathogenic bacteria [84].
A relationship between probiotic administration and the production of short chain fatty acids has been reported in animal models in a study published by Nagpal et al. [96] in 2018. The results show that probiotics administration led to an increase in short chain fatty acids production, improving the intestinal microbiota function.
1.2. Role of Probiotics in Improving Intestinal Motility
Numerous studies have demonstrated improved transit in patients with constipation. Administration of Bifidobacterium lactis HN019 and Bifidobacterium lactis DN-173 010 decreased transit time in adult subjects with chronic constipation [85]. Both in vitro and in human studies, B. lactis HN019™ reduced intestinal transit time in functional constipation by modulating the gut–brain–microbiota axis, mainly by the serotonin signalling pathway, via short-chain fatty acids produced by bacterial fermentation. B. lactis HN019™ is thus a probiotic that can improve the intestinal dysmotility-related disorders [85,86].
Fermented dairy products containing Bifidobacterium lactis DN-173 010 both decreased abdominal distension and transit time in a cohort of IBS-C patients [87].
Daily administration of Bifidobacterium lactis decreased the incidence of functional disorders in patients with abnormal transit and flatulence.
The combination of Bacillus subtilis and Streptococcus faecium probiotics improved the symptoms of patients with IBS without diarrhoea [88]. A combination of probiotics containing Lactobacillus acidophilus, L. plantarum, L. rhamnosus, Bifidobacterium breve, B. lactis, B. longum, and Streptococcus thermophilus improved symptoms in patients with IBS-D, with superior results and no notable adverse reactions [89].
A meta-analysis investigating randomized controlled trials concluded that administration of Bifidobacterium lactis decreased transit time in patients with chronic constipation [83,97,98,99,100].
A meta-analysis published in 2022 by Zhang et al. [101] suggests that B. coagulans is highly effective as a therapeutical agent for IBS-D patients, improving symptoms and quality of life. In this study, B. coagulans ranked as the most effective probiotic in improving abdominal pain and straining scores. Moreover, it retained its substantial efficacy even compared to multiple types of probiotics combinations. The authors emphasize the need of future research regarding this species, suggesting that obtaining specimens with higher biological function by means of genetic engineering and development of probiotic combinations containing B. coagulans may represent future research targets [101].
1.3. Role of Probiotics in Visceral Hypersensitivity
Several studies on animal models have shown that probiotics exert a direct antinociceptive effect on gut sensitive nerve endings, through bacterial metabolites acting as neurotransmitters [102,103].
Other experiments support the hypothesis that probiotics also act by modulating the balance between nociceptive and antinociceptive stimuli at CNS level.
Administration of dairy products containing Bifidobacterium animalis subsp. Lactis, Lactobacillus bulgaricus, Lactococcus lactis, and Streptococcus thermophiles in healthy individuals, was correlated with significant changes in affective, viscerosensitive and somatosensitive cortical processes, on MRI studies. Therefore, a link between probiotics and the activity of the emotional processing centre was suggested [90,91].
1.4. Probiotics and the Modulation of Inflammatory and Immune Processes
The connection between IBS and the inflammatory and immune response of the intestinal mucosa is indirectly suggested by the appearance of IBS symptoms after a bacterial or viral intestinal infection.
A series of studies have shown that IBS is accompanied by an alteration of the non-specific and specific immune response both local and systemic [104,105]. Increased permeability of the intestinal mucosa is considered a marker of local inflammation [33].
Non-specific immune local reaction is highlighted by the subepithelial accumulation of mast cells, macrophages, and dendritic cells (acting as antigen-presenting cells).
Non-specific systemic immune response translates into increased levels of certain cytokines: IL-1b, IL-6, IL-8, IL-12, and TNFα [106,107].
A decrease of anti-inflammatory cytokine IL-10, a regulatory cytokine that inhibits both the release of pro-inflammatory cytokines and antigen presentation, was also observed; thus IL-10 is proposed as a strong anti-inflammatory biological therapy for IBS [108].
Numerous laboratory findings and clinical study findings demonstrate that probiotics reduce the inflammatory and immunological response in IBS through a number of different pathways. The normal permeability of the epithelial barrier is maintained by probiotics, which also correct the imbalance between pro-inflammatory and anti-inflammatory cytokines (measured by the IL-10/IL-12 ratio) and reduce the local and systemic levels of several pro-inflammatory cytokines (TNF-a, IFN-g) [92,93].
1.5. Role of Probiotics in Stress Response
Numerous experimental and clinical data show that there are bidirectional influences between the microbiota and the CNS. Dysbiosis can induce alteration of the microbiota-GBA, while probiotics can contribute to the normalisation of this interaction [109].
Several studies have highlighted the protective effect of probiotics against anxiety-depression status induced by mental stress. Some probiotics (Lactobacillus rhamnosus and Lactobacillus helveticus strains) normalised the exaggerated response of the HPA in IBS [110].
Lactobacillus rhamnosus decreased the stress-induced corticosterone release by modulating GABA receptors involved in anxiety, decreasing the incidence and severity of abdominal pain episodes in patients with IBS [111,112,113,114].
A strain of Bifidobacterium longum had positive effects in a recent study conducted by Sabate et al. [93], who concluded that thirty days of B. longum 35624 treatments reduced the severity of the disease and improved the quality of life of patients with IBS, especially those with severe forms. Stress-reduction induced by Bifidobacterium is most-likely related to tryptophan metabolism, as increased levels of tryptophan were observed after probiotic administration [115].
A mixture of strains from eight probiotic species (Bifidobacterium longum, B. breve, B. infantis, Lactobacillus casei, L. acidophilus, L. plantarum, L. delbrueckii subsp. Bulgaricus and Streptococcus salivarius) led to an increase in brain-derived neurotrophic factor (BDNF) level [94]. Dysfunctions in the epigenetic control, transport or signalling cascades of BDNF have been discussed regarding various neurological and psychiatric diseases [116]. There is also growing evidence of an important role played by BDNF in visceral pain and VH [117,118,119].
2. Role of Prebiotics in IBS Pathogenesis and Management
Prebiotics are “substrates that are selectively used by host microorganisms that confer a health benefit on the host”. Prebiotics are usually dietary carbohydrates. Inulin fructans (ITFs) (fructose polymers) and galactooligosaccharides (GOS) (galactose polymers) are the most widely studied [120]. Extensive studies have demonstrated that prebiotics have the ability to specifically increase Bifidobacteria in healthy subjects [121]. In addition, prebiotics increase faecal short-chain fatty acids and decrease inflammatory markers [122], thus providing their role in symptom management in IBS.
One of the most exhaustive meta-analyses on the role of prebiotics in IBS therapy, published in 2019 by Bridgette Wilson et al. [123], concluded that prebiotics did not improve gastrointestinal symptoms, outcome, or quality of life in patients with IBS, but increased faecal Bifidobacteria. However, the administration of a galactooligosaccharide prebiotic for four weeks in patients with IBS and anxiety led to a decrease in symptoms and an improvement in quality of life [124]. Also, the dose and duration of administration did not improve the general symptoms, with individual differences between type and dose being observed. Non-ITF prebiotics improved flatulence while ITF prebiotics worsened flatulence; doses ≤ 6 g/day reduced flatulence, whereas higher doses had no effect [123].
Short-chain fructooligosaccharides (scFOS) were also studied by Azpiroz et al. [125], who described the influence of prebiotics on anxiety in IBS individuals.
Niv et al. [126] proved the efficacy of partially hydrolysed guar gum (PHGG) for patients with IBS accusing mainly bloating, without any side effects. However, it showed no effect on the rest of the possible IBS symptoms.
However, prebiotic therapy must be further investigated, as the results of the studies carried out so far are unconcluded [127].
This entry is adapted from the peer-reviewed paper 10.3390/gidisord5040043
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