Probiotics, Prebiotics, and Synbiotics in the Irritable Bowel Syndrome Treatment: A Review

Irritable bowel syndrome is not a life-threatening disease, yet it significantly affects the quality of life and contributes to economic loss. It is estimated that even up to 45% of the world’s population can suffer from the disease. The first attempts to diagnose irritable bowel syndrome were made at the end of the 19th century; however, establishing appropriate diagnostic criteria and treatment methods is still ongoing. To date, little is known about the etiology of irritable bowel syndrome; however, growing attention is drawn to the intestinal microbiota as a factor in the disease development. For this reason, researchers have conducted many studies on therapies that modulate the microbiota, among which probiotics, prebiotics, and synbiotics are widely studied. To date, most studies have examined probiotics; however, there are also several studies demonstrating the efficacy of prebiotics and synbiotics. The aim of this review was to summarize findings on the usefulness of probiotics, prebiotics, and synbiotics in the treatment of irritable bowel syndrome.


Introduction
Irritable bowel syndrome (IBS) is an intestinal functional disorder that is classified as a non-life-threatening disease. It causes a decline in life quality and abates an ability to function in society, as well as attributes to economic losses [1,2]. The cost of IBS is estimated to be up to EUR 8 billion in Europe, nearly USD 2 billion in China, and up to USD 10 billion in the United States of America [1]. It is predicted that up to 10% of the worldwide population suffers from this disease. Some sources estimate an even higher prevalence reaching 45% [1,3]. Women are 1.5-3 times more likely to develop IBS than men, with a two times higher possibility of constipation-associated symptoms, whereas men exhibit a diarrheal form of the condition [4].
Based on the manifestation of the disease, IBS is divided into four subtypes, namely, forms with predominant diarrhea (IBS-D), with prevailing constipation (IBS-C subtype), or mixed defecation types (IBS-M), as well as IBS that cannot be subdivided [5,6]. Besides altered bowel habits, IBS patients may also suffer from abdominal pain or discomfort, flatulence, nausea, dyspepsia, or reflux [7].
The etiology of IBS is still unknown. However, many factors could be responsible for the development of the disease. Besides psychological disturbances, the altered intestinal motility, food hypersensitivity, genetics, abnormalities of the intestinal microbiota, and impairment of the bidirectional communication pathways between the gut, its microbiota, and the central nervous system, called the gut-brain axis (GBA), could trigger the disease [8,9]. Moreover, bacterial overgrowth or post-infectious (PI) changes in the gastrointestinal tract (GIT) and inflammation are acknowledged as IBS initiators [10]. Physical or sexual abuse in childhood, a short period of breastfeeding, food allergies, obesity, or surgical interventions might also lead to the evolvement of the disease [6]. IBS patients are more prone to exhibit psychological disorders, such as anxiety or depression. This makes them less receptive

Method
The literature search was conducted until June 2021 in the PubMed Central database. Terms: "IBS", "Irritable Bowel Syndrome", "Irritable Bowel", "IBS AND Microbiota", "Irritable Bowel AND Microbiota", "IBS AND Probiotics", "Irritable Bowel AND Probiotics", "IBS AND Prebiotics", "Irritable Bowel AND Prebiotics", "IBS AND Synbiotics", "Irritable Bowel AND Synbiotics" were used in the field of article's title, abstract, as well as keywords. We included studies of all types and did not restrict the search by publication date or IBS diagnosis criteria.

History of the Illness Recognition
The history of the IBS diagnosis began in 1871 when da Costa described a condition called membranous enteritis in which patients suffered from intestinal pain accompanied by excretion of mucus [20,21]. Doctor Hale-White, who studied patients with various conditions of organic origin (e.g., colon cancer, ulcerative colitis, or appendiceal abscess), mentioned the disease at the beginning of the 20th century [22]. On the other hand, when doctor Herbert P. Hawkins (1906) analyzed reasons for the misdiagnosis of appendicitis, he concluded that there are several symptoms associated with intestines functionality, which do not have an origin in any pathological changes. The scientist speculated that constipation, diarrhea, intestinal spasms, and abdominal pain can have a nervous etiology [23]. Doctor John R. Ryle investigated a similar problem, which he termed spastic colon, as he also observed a number of unnecessary abdominal surgeries that failed to provide relief to patients suffering from chronic abdominal pain. He emphasized the vital importance of a detailed diagnosis, focusing on continuous pain, not typical for acute enteritis or bowel obstruction, as well as unusual palpability of patients' colon caused by muscle spasm [24]. In 1937, doctor Earle P. Scarlett agreed that Ryle's term "spastic colon" was more appropriate, rather than "colitis", which should be used only in cases of clearly demonstrated inflammation of the colon. Additionally, the "irritable colon" appellation, first introduced by doctor Sippy, was mentioned as the equally appropriate term for this spectrum of symptoms. Although, doctor Scarlett pointed out that the disturbance of functionality might not only affect the colon but the whole intestines [25]. In the following years, IBS was found to be related to the overstimulated autonomic nervous system and patients' personality, which, together with X-ray examinations and observations of symptomatology, led to correct diagnostics [26]. Furthermore, Misiewicz, Wallet, and Eissner (1966) observed the impact of elevated levels of 5-hydroxytryptamine (5-HT, serotonin), an amine produced in the alimentary tract, on intestinal motility resulting in diarrhea. It marked the beginning of extensive studies on the role of serotonin in the etiology of IBS [27]. Moreover, the role of the gut microbiota in IBS etiology has been extensively analyzed since the 1980s [28]. It was not until the late 1990s that gastroenteritis was found to be a contributing factor to the development of IBS [29,30]. However, the differences between the fecal microbiota of healthy individuals and IBS patients were not described until the early 2000s [31,32].
In 1962, Chaudhary and Truelove, who studied IBS as a spectrum including both mucus colitis and spastic colon, divided 130 patients into those with painless diarrhea and ones with abdominal pain, among whom Ritchie and Tuckey (1969) observed similarities in colon motor activity, although bowel function ranged from normal to diarrhea or constipation [21,22]. Meanwhile, Connell (1968) described diagnostic criteria based on the combination of symptoms such as abdominal pain and bowel function abnormalities without pathological changes [33]. Ritchie (1970) added the sensitivity of the colon while being pressured, as well as the profuse excretion and transition of the mucus to the list of typical symptoms [21]. Both researchers stressed the significance of excluding other gastroenterological diseases that might present with similar manifestations [21,33]. Moreover, Manousos et al. (1967) analyzed intestinal content transition time in 75 individuals with irritable colon syndrome, 43 patients with diverticulosis, and 88 subjects who had no abnormalities in bowel functions. The results showed that people suffering from both irritable colon and diverticulosis had a shortened transition time of food through the digestive tract. The researchers believed it might be related to a disturbance in colonic muscle function [34]. However, Cann et al. (1983) noted changed food transition time not only in the colon but also in the small intestine. It proved that IBS should be considered a disease affecting the whole intestine. The researchers also described that individuals with constipation had a prolonged transition time of intestinal content, whereas diarrheic ones shortened [35].
Since 1978, researchers and physicians have referred to the criteria described by Manning et al. (1978). They included flatulence, pain relief after intestinal movement, frequent and looser stools, the presence of mucus, or the impression of incomplete defecation as a highly possible differentiation of IBS from organic diseases [36]. A few years later, Kruis drew attention to the duration of symptoms as an essential diagnostic criteria, which was not universally accepted [37]. Subsequently, the Rome criteria for IBS were first presented at the 13th Rome Congress in 1988 and published as a result of Thomson, Drossman, Heaton, Dotteval, and Kruis collaboration [38]. The Rome Committee continued its work on the proper definition and diagnosis of IBS, which was amended in 1992, 1999, and 2006. The latest version was presented in 2016 as the Rome IV criteria. It states that IBS must manifest with abdominal pain relapsing at least one day per week for the past three months, began at least six months before diagnosis, and correlate with no less than two of the following criteria: being linked to defecation, be associated with shifts in stool regularity and/or its form [37]. Besides the typical symptoms of IBS, nausea, vomiting, heartburn, or even anxiety, insomnia, or depression have been observed in some patients suffering from the disease [39].
As more became known about IBS, more attention was paid to the treatment methods. In 1966, doctor MacDougall recommended a psychological and physical approach to managing the disease. This included reducing bowel stimulation through a diet adapted to the observed symptoms, the use of pharmaceuticals (e.g., codeine phosphate, diphenoxylate, propantheline), and reducing stress [40]. Later, in 1977, Diamant published a review on irritable colon syndrome in which he analyzed the latest reports on the treatments of the disease. The researcher drew attention to the importance of psychological factors since almost 50% of patients responded positively to placebo in various trials. However, Dotevall and Groll (1974), in their studies on mepiprazole, a type of tranquilizer, found that the placebo was ineffective after some time compared to the analyzed substance. In addition to tranquilizers, antispasmodic drugs such as anticholinergics or mebeverine, as well as agents to increase stool mass, were also prescribed by physicians for patients with IBS, either individually or as a combination of treatments [41]. Diamant (1977) also suggested that a low-fiber diet may be responsible for the development of the syndrome. The researcher proposed the adjustment of the dosage of dietary fibers to the observed symptoms of patients as an approach to treat the disease [42]. Nowadays, the European Food Safety Authority (EFSA) defines dietary fibers as non-digestible carbohydrates, such as pectins, cellulose, resistant starch, and non-starch polysaccharides, or fructooligosaccharides, as well as lignin [43]. At the end of the 20th century, psychological treatments (e.g., psychotherapy, behavioral or group therapy, and hypnotherapy) and the exclusion of certain foods, were also acknowledged as an additional or alternative approach to the medical treatment of IBS [44]. Simultaneously, preliminary studies of agents modifying 5-HT receptors' functionality had begun [45]. To date, the greatest interest in the pharmacological management of IBS patients is focused on receptor subtypes 5-HT 3 and 5-HT 4 due to their impact on the functionality of GIT [46]. In the early 2000s, it was hypothesized that 5-HT 3 receptor antagonists such as ondansetron and granisetron might be effective in IBS treatment, while cilansetron was already approved for use [47]. Moreover, studies have been conducted on 5-HT 4 receptor agonists, namely, tegaserod or prucalopride [48]. Currently, new 5-HT 3 receptor antagonists and 5-HT 4 receptor agonists are still being sought [49,50].
Since the late 1970s, researchers have searched for natural ways of symptomatic treatments of IBS because of the side effects associated with prolonged pharmaceutical treatment. One of the alternatives was peppermint oil, whose antispasmodic properties were observed both in vitro and in vivo by Rees et al. (1979) [51]. However, it was not until the turn of the 20th to the 21st century that probiotics began to be investigated as a means of treating IBS [28]. Furthermore, Hunter et al. (1999) initiated studies on prebiotics as management of IBS [52]. Nowadays, synbiotics are also a subject of interest in IBS management analysis. However, even after 2010, there was not much data available on synbiotics' impact on gastrointestinal disorders [53,54]. To date, research groups have focused on probiotics, prebiotics, and synbiotics as means to help IBS patients.

Intestinal Microbiota in Patients with Irritable Bowel Syndrome
Human GIT is colonized by up to 10 14 organisms belonging to about 1000 species, among which prokaryotes (bacteria and unicellular microbes) dominate. However, fungi, archaea, parasites, and viruses are also inhabitants of the gut [55,56]. Bacteria residing in the GIT are mostly classified into four phyla, namely, Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria [57]. Differences in the GIT microbiota of individuals can be attributed to the type of delivery and feeding of the infant, age, sex, diet, sanitary and living conditions, health issues, and administrated pharmaceuticals, as well as geographical regions [58]. Nevertheless, dysbiosis of the GIT microbiota can trigger immune system responses that result in inflammation in the gut and disruption of the GBA [59]. The imbalance of the gut microbiota, which may be associated with overgrowth or lack of certain microorganisms, or genetic abnormalities, can lead to a variety of cardiovascular, neurological, or intestinal diseases, one of which is IBS [19,57]. Pittayanon et al. (2019) conducted a systematic review of 24 studies on the microbiota of IBS patients and observed significant differences in the results. These researchers found that in some studies, the number of potentially harmful bacteria from Enterobacteriaceae family and Bacteroides genus was increased. Simultaneously, a decrease in the prevalence of representatives of the beneficial microbiota, namely, genus Bifidobacterium and Faecalibacterium, was observed in individuals with IBS compared to the healthy ones [60]. Chong et al. (2019) made analog observations in their review. Additionally, the article mentioned the increased number of bacteria belonging to Firmicutes phyla, including Lactobacillus and Ruminococcus genus, as well as a decreased abundance of Erysipelotrichaceae and methanogens in IBS patients [61]. Mei et al. (2021), who analyzed only IBS-D patients in China, also observed elevated abundance of bacteria belonging to Enterobacteriaceae family, as well as Proteobacteria phyla, and decreased prevalence of Firmicutes, Fusobacteria phyla, and Alloprevotella, Fusobacterium genus in contrast to the healthy population [62]. Tap et al. (2017) observed the correlation between the severity of IBS and the number of Methanobacteriales capable of producing methane, which is linked to the occurrence of constipation [63]. In addition, the research group noted the reduced number of bacteria from Prevotella genus in IBS patients compared to healthy subjects. However, Su et al. (2018) and Barandouzi et al. (2021) found increased abundance of this genus in IBS individuals [63][64][65]. What is more, Shukla et al. (2015) found a lower abundance of Bifidobacterium and Lactobacillus genus and increased prevalence of Veillonella genus, Clostridium coccoides, Bacteroides thetaiotamicron, Ruminococcus productus, and P. aeruginosa [66]. Although several studies have described an increased ratio of Firmicutes to Bacteroidetes in patients with IBS compared to healthy individuals, Barandouzi et al. (2021) observed a similar abundance of bacteria belonging to these two phyla, that constitute about 90% of the total microbiota of GIT [65,67]. This research group observed, among IBS patients, a higher prevalence of bacteria belonging to Verrucomicrobia phyla, as well as from Blautia genus, which is acknowledged as a marker of microbiota imbalance [65]. Similarly, Lee et al. (2021) found no significant differences in phyla levels in fecal samples of IBS patients and healthy population. However, these researchers observed an increase in pathogenic bacteria from Desulfovibrionaceae family, and a simultaneous decrease in the beneficial Lachnospiraceae family [68]. On the contrary, Ahluwalia et al. (2021) did not notice any differences between the fecal microbiota of IBS and healthy individuals. They concluded the variations were likely related to microbiota functionality rather than composition [69]. Moreover, Dlugosz et al. (2015) reported no significant differences in the small intestine microbiota of IBS and healthy subjects [70].
Despite the efforts of researchers to find the dysbiosis patterns in the microbiota of people suffering from IBS, there are still many inconsistencies in the obtained results. It could be due to different GIT parts from which samples were gathered, different analytical methods, or even population disparity [71].

Probiotics, Prebiotics, and Synbiotics in IBS Treatment
Growing evidence of GIT microbial population disturbances and gastroenteritis being factors of IBS development resulted in the search for therapies based on microbiota manipulations. For this purpose, probiotics, prebiotics, and synbiotics could be used [72,73]. To date, researchers have carried out multiple studies on the impact of various probiotic strains, prebiotics, and their mixtures on people suffering from IBS. A few studies were conducted on animal models which can be applied if the etiology of the induced disease is as similar as possible as it is in humans. These models play an important role in pre-clinical research on the treatment or mechanisms of functional gastrointestinal disorders, including IBS [74]. Since psychological pressure might cause the development of IBS or provoke its symptoms in humans, stress is an inducing factor for most animal models. Nevertheless, IBS might emerge in individuals after infections; therefore, the post-infectious animal models are also used, which are caused by pathogenic bacteria or parasites. Chemical or mechanical stimulation might also trigger IBS symptoms in rodents [75].

Probiotics
The probiotic effect is attributed to the strain and even two different strains of the same species might impact the patient to various extension [76,77]. Therefore, the influence of one probiotic cannot be extrapolated to another one from the same species or even to a different strain [78]. Moreover, probiotics can act differently in various populations, as well as stages and types of diseases [77,78].
In 2002, Sen et al. published a study on the influence of Lactobacillus plantarum 299V on IBS patients. The strain did not exhibit any beneficial effect on the disease symptoms [79]. On the contrary, Ducrotté et al. (2012) described the potentially beneficial impact of the strain on the IBS symptoms of studied subjects [80]. Nevertheless, the research conducted by Sen et al. (2002) was not the only one leading to the conclusion that tested probiotic might not be effective in IBS treatment [79]. Pedersen [95]. What is more, Lb. gasseri BNR17 has been described by Kim et al. (2018) as suitable for use as IBS treatment since it improved its symptom [96]. Shin et al. (2018) analyzed the same strain and noted its impact on intestinal microbiota, as well as bowel habits of trial participants [97]. Lb. casei is yet another species from Lactobacillus genus, which researchers studied as probiotics in IBS treatment [98,99]. Compare et al. (2017), who performed ex vivo analysis on ileal and colonic mucosa culture tissue model harvested from PI-IBS-D patients, established that Lb. casei DG is able to diminish mucosal inflammation [98]. On the other hand, Seong et al. (2021) conducted a study on a rat IBS model induced with chronic restrain stress. Those researchers also observed the capability of Lb. casei DKGF7 to decrease inflammatory cytokines in colonic tissue, as well as serum corticosterone levels, along with amelioration of IBS symptoms and increased expression of tight junction proteins [99]. conducted human studies and noted that Lactolevure ® probiotic, including S. boulardii, B. lactis BB-12, Lb. acidophilus LA-5, and Lb. plantarum, can be effective in attenuation of bloating and abdominal pain severity, especially in patients with IBS combined with small intestinal bacterial overgrowth (SIBO) [112]. Reduction of SIBO was also observed by Barret et al. (2008), who studied Yakult ® dairy product containing Lactobacillus casei Shirota. This probiotic also decreased the early rise in breath hydrogen after lactulose (ERBHAL), and, simultaneously, abdominal pain [113]. Lee et al. (2018) described the comparable observation concerning the influence of probiotic on SIBO. Their trial involved only IBS-D patients treated with a multi-strain probiotic (Ther-Biotic ® Complete) containing S. thermophilus, along with strains belonging to Lactobacillus spp. (7) and Bifidobacterium spp. (4) [114].

Prebiotics
At present, only a few pieces of research on the impact of prebiotics on the health improvement of people suffering from IBS have been conducted. Therefore, this area of study is still in need of investigation.
The first study on the influence of prebiotics on IBS management was published in 1999 by Hunter et al., who analyzed the oligofructose, the effect of which was marginal and only in patients with IBS-C [52]. Similarly, Olesen et al. (2000), who studied fructooligosaccharides (FOS), did not conclude whether use of prebiotic helped to improve the condition of IBS patients or not [128]. Short-chain FOS (scFOS) was also studied by Azpiroz et al. (2016), who described the influence of the prebiotic on the anxiety level of IBS individuals and Bifidobacterium spp. count in their stool [129]. Silk et al. (2009) tested the effectiveness of another prebiotic, namely, the trans-galactooligosaccharide (GOS) mixture produced by Bifidobacterium bifidum NCIMB 41171 from lactose. They observed that it not only relieved symptoms such as flatulence, abdominal pain, and discomfort, as well as stool patterns but also increased the number of Bifidobacterium spp. in fecal samples [130]. Both GOS and FOS, along with inulin and anthocyanins, were included in the preparation used in the trial conducted by Chen et al. (2017) in the IBS mice model. The product exhibited the ability to diminish inflammation and improve the intestinal barrier. Additionally, if used prior to infection, it could help to establish PI microbial homeostasis in the GIT. Nonetheless, the blend of prebiotics needs to be further investigated in humans [131]. Niv et al. (2016) proved the effectiveness of partially hydrolyzed guar gum (PHGG) for IBS patients suffering mostly from gasses and bloating. The use of this compound did not cause any side effects. However, it did not exhibit any influence on the rest of the possible IBS symptoms [132].
All of the cited research was placebo-controlled [52,[128][129][130]132], except from animal studies described by Chen et al. (2017) [131]. Among mentioned human trials, only ones conducted by Olesen et al. (2000) [128], and Silk et al. (2009) [130], were not carried out in a double-blind system. However, the study design by Silk et al. (2009) was the only one including the influence of a dose on prebiotic effectiveness in IBS therapy [130]. Research carried out by Hunter et al. (1999) and Olesen et al. (2000) did not differentiate IBS subtypes [52,128] [129,130,132]. Details of the above-mentioned research are presented in Table 2.

Synbiotics
Despite the concept of synbiotics being introduced in 1995, and the first attempts to recognize IBS were made at the end of the 19th century, the idea of using these preparations to treat the disease appeared in the last decade [133].
In 2013, Cappello et al. performed the first analysis of Probinul ® and its impact on IBS individuals. The synbiotic included inulin, tapioca-resistant starch, and Lactobacillus spp. (6) and Bifidobacterium spp. (2) strains, as well as Streptococcus thermophilus. Probinul ® did not diminish flatulence and bloating to the satisfying level according to participants of the trial [134]. Shavakhi et al. (2014), who studied the impact of Balance ® , which included FOS, and probiotic strains from Lactobacillus (4) and Bifidobacterium (3) genus, as well as S. thermophilus, did not observe any influence of the preparation on IBS patients [135]. Similar results were obtained by Bogovič Matijašic et al. (2016), who studied synbiotic fermented milk product containing Lb. acidophilus La-5, B. lactis BB-12, and 2% dietary fiber (Beneo Orafti Synergy1; 90% inulin, 10% oligofructose) [136]. On the contrary, Bucci et al. (2014) noted the attenuation of flatulence in IBS subjects after 4 weeks of the disease treatment with Probinul ® , which was sustained during a 6 months period of therapy [137]. Another synbiotic, namely, Lactol ® , including B. coagulans and FOS, was tested by Rogha et al. (2014). The research team noted relief of abdominal pain, discomfort, and diarrhea in IBS individuals; however, no improvement in constipation-related symptoms was observed. Nonetheless, the study revealed some side effects of the preparation; therefore, its safety has to be further evaluated [54]. Although, Asgarshirazi et al. (2015), who analyzed the effectiveness of Lactol ® in treating functional abdominal pain in children, did not notice any side effects of the preparation [138]. Moser et al. (2019) conducted a study on the impact of yet another synbiotic preparation named OMNi-BiOTiC ® Stress Repair on IBS-D patients. The preparation comprised prebiotics, namely, corn starch, maltodextrin, inulin, and FOS, along with Lactococcus lactis W19, Lactobacillus spp. (5), and Bifidobacterium spp.
(3) strains. Results showed a positive influence of the mixture on mucosal microbiota diversity and concentrations of acetate and butyrate in fecal samples [139]. Lee et al. (2019) studied the impact of another synbiotic preparation, containing inulin, FOS, and probiotic strains from Lactobacillus (6) and Bifidobacterium (2) genus on IBS patients. The research team observed improvement in bloating, fatigue, and abdominal discomfort in trial participants [140]. On the other hand, Min et al. (2012) and Bahrudin et al. (2020) analyzed the influence of synbiotic dairy products, such as yogurt with the addition of Bifidobacterium animalis subsp. lactis Bb-12 and acacia dietary fiber, and drink containing Lb. helveticus and polydextrose as a prebiotic, respectively, on IBS subjects [141,142]. Min et al. (2012) described that the studied product could attenuate symptoms of the disease in both IBS-C and IBS-D patients [141]. Bahrudin et al. (2020) observed the beneficial effect of synbiotic only in studied IBS-C individuals. Nevertheless, the researchers concluded that probiotic strain alone is the active agent [142]. The effective mixture of pro-and prebiotics for IBS-D patients, which reduce the feeling of incomplete intestinal movements, release abdominal pain, and help to regulate stool patterns, have been described by Skrzydło-Radomańska et al. (2021). The synbiotic comprised probiotics, namely, Lb. rhamnosus FloraActive-19070-2, Lb. acidophilus DSMZ 32418, B. lactis DSMZ 32269, B. longum DSMZ 32946, B. bifidum DSMZ 32403 strains, and scFOS as a prebiotic compound [143]. Last but not least, in 2020, Seong et al. described a synbiotic, containing Lb. paracasei DKGF and Opuntia humifusa extract as a prebiotic, effective in IBS murine model. Nevertheless, its functionality must be further assessed in humans [144].

Summary
In conclusion, the use of probiotics, prebiotics, and synbiotics in IBS treatment is still in need of investigation and standardization. Researchers focused mostly on probiotics, especially multi-strain ones, creating a demand for new research on prebiotics, and synbiotics in the management of IBS.
The vast majority of trials are double-blind and placebo-controlled; however, there are still studies conducted in an open-label system, as well as with no control or placebo group, which could bring unreliable results. Additionally, analyzed preparations differ in probiotic strains, their number, and density, as well as amount and type of prebiotic or their combination, in the case of synbiotics. Moreover, the dosage of studied preparations varied among research, and its impact is rarely analyzed. Most of the trial designs would benefit from a longer treatment period and additional follow-up phase since this aspect is mostly described by researchers as a study limitation. Another obstruction of research might be the number of participants that rarely exceeded 100. However, this obstacle is hard to avoid because individuals are entering the trials voluntarily. Lastly, not every probiotic, prebiotic, and their combination would be an appropriate mode of treatment for each IBS subtype, which also needs to be studied in more detail.
Nevertheless, the last two decades of research on probiotics, prebiotics, and synbiotics bring satisfying results and they are acknowledged as effective and safe in IBS therapy. These preparations can be introduced as an alternative to drugs that might carry a risk of side effects, especially in long-term use. Among the field of microbiota-manipulation-based therapies, probiotics, prebiotics, and synbiotics are a promising direction of alleviation of symptoms for people suffering from IBS.