Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, which affects 10 – 22% of the UK population and is responsible for 20 – 50% of the workload of gastroenterology departments . IBS is characterised by altered bowel habit, pain, and wind or bloating, which all severely affect quality of life and may last for decades. IBS can be classified into subgroups depending on the predominant bowel symptom, namely constipation-predominant (IBS-C), diarrhoea-predominant (IBS-D) or alternating between the two (IBS-A) [2, 3]. Post-infectious (PI) IBS may arise after an episode of acute gastroenteritis .
The causes of IBS remain poorly understood, and include altered gut motor function, visceral hypersensitivity, abnormal gas handling, alterations in the central nervous system, mild inflammation, disturbances in serotonin handling and genetic factors (reviewed in ). Evidence has been mounting in the past decade that alterations in the gastrointestinal microbiota may also play a role in IBS. An early study showed that patients with IBS-D excreted abnormally high levels of hydrogen compared to healthy individuals, suggesting that there was abnormal bacterial fermentation of ingested foods . An exclusion diet reduced this. More recently the gastrointestinal microbiota of IBS patients have been compared with those from healthy subjects by bacterial culture or molecular approaches [reviewed in [7, 8]. Many studies have found alterations in the numbers of bacterial species present, or in the abundance of particular bacterial species. The findings vary, but a common feature seems to be a reduction in the number of Bifidobacteria and increased numbers of Firmicutes and Enterobacteriaceae in samples from IBS patients compared to control samples.
IBS has also been linked to small intestinal bacterial overgrowth, [reviewed in [7, 9, 10], although this is currently somewhat controversial . In SIBO, bacterial numbers can rise from normal levels of 100-4 colony forming units (cfu) of bacteria/ml in the terminal jejunum, 100-5 cfu/ml in the proximal ileum and 105-8 cfu/ml in the terminal ileum [11, 12] to 1011 cfu/ml . SIBO is currently defined as the presence of ≥ 1 × 105 cfu/ml of colonic bacteria in the jejunum [13, 14]. In contrast to the normal situation in which digestion and absorption of food is complete before the bolus reaches bacteria in the colon, in patients with SIBO, ingested food comes into contact with bacteria in the jejunum and ileum, and is fermented to produce gas, which has been visualised in the small intestine by abdominal radiography . SIBO is typically diagnosed by giving patients a drink containing a poorly digestible sugar such as lactulose, and analysing their breath gases at intervals (reviewed in [16, 17]). Glucose can also be used. The main gases excreted are hydrogen, which is associated with IBS-D, and methane, which is associated with IBS-C [18–21]. In one study, 78% of IBS patients tested positive for SIBO using the lactulose hydrogen breath test (LHBT) .
There is currently some controversy surrounding the use of lactulose hydrogen breath tests to diagnose SIBO and, consequently, the role of SIBO in IBS. Early breath tests diagnosed SIBO if hydrogen was excreted in two bursts, corresponding to bacterial fermentation in the small intestine, and in the colon. Later, hydrogen excretion within 90 minutes of lactulose ingestion was taken as diagnostic of SIBO. However, a recent study has combined LHBTs with scintigraphy to follow the movement of a radiolabelled tracer through the gastrointestinal tract . Hydrogen excretion within 90 minutes of lactulose ingestion was found to correlate with fast oro-caecal transit rather than SIBO , and it has been suggested that glucose would be a better fermentation substrate since it is absorbed before it reaches the colon [17, 21, 24]. Using the ability to culture 1 × 105 colonic bacteria from duodenal or jejunal aspirates as the gold standard for SIBO diagnosis, SIBO was diagnosed in 4% of IBS patients and healthy control subjects in one study  and in 10.9% of IBS patients in another . Modestly raised bacterial counts (≥ 1 × 103 cfu/ml) were found in 43% of IBS patients compared to 12% of healthy controls in the first study  and 37% of IBS patients in the second , suggesting that perhaps a more modest overgrowth of bacteria than previously thought might contribute to IBS. Of note, lipopolysaccharide from Gram-negative bacteria speeds up gastrointestinal transit , raising the possibility that modest numbers of bacteria in the small intestine could speed up transit of lactulose (and chyme) to the colon, and result in a positive LHBT (and IBS) without fermenting the lactulose themselves.
One Gram-negative bacterium that has been implicated in IBS and SIBO is Escherichia coli. An early study found E. coli throughout the gastrointestinal tract of patients with SIBO . E. coli was present in jejunal and duodenal aspirates from patients with IBS and SIBO [14, 25], in addition to Klebsiella and Enterococcus species. E. coli was found to be more prevalent in the mucosal microbiota of IBS patients than those of healthy control subjects when biopsy specimens were labelled with fluorescent in situ hybridisation probes , and enteroaggregative strains of E. coli were present in higher numbers in faecal samples from IBS patients than those from healthy individuals .
There are currently various medicines available to treat IBS, including fiber, antispasmodic agents, and antidepressants to modulate pain perception . Tricyclic antidepressants block diarrhoea whereas serotonin reuptake inhibitors can benefit IBS-C patients by stimulating gastrointestinal motility . In agreement with the idea that alterations in the gastrointestinal microbiota are involved in IBS, there has been considerable success with treatments that reverse this. Clinical trials have shown that antibiotics can be effective in treating IBS [31, 32]. Successful eradication of SIBO, and reversal of the symptoms of IBS have been achieved by treating IBS patients with antibiotics such as metronidazole , neomycin , the non-absorbable antibiotic rifaximin (reviewed in ), a combination of rifaximin and ciprofloxacin , or a combination of rifaximin and neomycin for IBS-C patients who produce methane . Reduction of hydrogen or methane excretion was linked to improvement in gastrointestinal symptoms and rifaximin was particularly effective in treating wind and bloating. Currently, NICE guidelines do not mention the use of antibiotics for the treatment of IBS in the UK . SIBO can return after treatment, however  and there is concern that widespread and prolonged treatment with antibiotics could lead to the emergence of antibiotic resistant bacterial strains . Indeed rifaximin can be used to treat infections with Clostridium difficile, but rifaximin-resistant strains have been isolated , and the fact that some IBS patients are carriers of C. difficile raises the possibility that widespread treatment of IBS patients with rifaximin could lead to the production of more rifaximin-resistant strains of C. difficile.
In contrast, the use of probiotics aims to increase the number of beneficial bacteria. Probiotics are live microorganisms that, when administered in sufficient numbers, reduce visceral hypersensitivity, improve gastrointestinal dysmotility and epithelial integrity, improve immune function, and modulate the gut microbiota [7, 8]. Two recent systematic reviews showed that probiotics had a moderate therapeutic benefit in improving IBS symptoms [43, 44]. Probiotics reduced the pain of IBS and this was statistically significant; there was also a significant reduction in flatulence and a trend towards reduction in bloating . In particular, lactic acid bacteria were shown to be useful, although the therapeutic benefit stopped when administration of the probiotics was terminated . Related to this, prebiotics have also been shown to be of modest benefit in treating IBS – these are nondigestible dietary supplements that increase the growth of beneficial bacteria. One clinical trial showed that ingestion of galactooligosaccharide stimulated the growth of bifidobacteria and alleviated IBS symptoms . Finally, faecal transplantation has been successfully used to modulate the gastrointestinal microbiota in a small number of IBS patients (reviewed in ). This has the advantage that the entire community of colonic bacteria is transplanted, rather than the one or two bacterial species that might be present in a probiotic preparation.
An alternative approach to the treatment of IBS is the use of dietary modifications to reduce the amount of fermentable substrates available to the gastrointestinal microbiota. Early work pioneered the use of an exclusion diet consisting of one meat, one fruit and distilled or spring water for a week. If the patient’s IBS symptoms resolved, foods were reintroduced one at a time and any resulting IBS symptoms noted . Two thirds of the patients reported resolution of their symptoms on the exclusion diet, and wheat, corn, dairy products, coffee, tea and citrus fruits were found to provoke IBS symptoms, even in a double blind food challenge. A more relaxed exclusion diet consisting of fish and meat (apart from beef) and rice, and lacking dairy products, citrus fruits, yeast, tap water and caffeinated drinks, reduced hydrogen excretion by IBS patients in addition to resolving their symptoms . This exclusion diet has been described in more detail . These and other exclusion diets have been found to be useful under medical supervision by NICE , which also recommended that it may be helpful for IBS patients to limit both their fibre intake, and to eat no more than three portions of fruit per day. A recent approach to dietary manipulation has rationalised knowledge of the foods that commonly provoke IBS symptoms with an understanding of their chemical composition, namely the adoption of a diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) . This involves avoiding 1) fruits that are high in fructose, 2) dairy products apart from butter and hard cheese, because they contain lactose, 3) vegetables, legumes and cereals (including wheat) that contain the oligosaccharides fructans or galactans and 4) fruits, vegetables and artificial sweeteners that contain polyols . Restriction of fructose and fructans led to an improvement in gastrointestinal symptoms in three out of four IBS patients with fructose malabsorption . When other patients who had attained remission of their IBS symptoms for 3 – 36 months on a low FODMAPs diet were rechallenged with fructose or fructans in a placebo-controlled, double blind clinical trial, their symptoms returned, indicating that the fructose and fructans could provoke IBS symptoms . In another double blind trial by the same group (in Australia), IBS patients on a high FODMAPs diet excreted more hydrogen and experienced more gastrointestinal symptoms than patients on a low FODMAPs diet . More recently, a British group has compared the efficacy of a low FODMAPs diet in reducing IBS symptoms with the standard dietary guidelines recommended by NICE: more of the patients on the low FODMAPs diet reported an improvement in their symptoms than the patients following the NICE dietary guidelines , this was especially true for wind and bloating.
Herbal medicines are also used to treat IBS, both in mainstream medicine, and in complementary and alternative medicines from different traditions; these have been discussed in several excellent reviews [54–56]. Peppermint (Mentha piperita) oil has been recommended for the treatment of IBS by NICE guidelines  and is widely prescribed in the form of enteric-coated peppermint oil tablets; it has antispasmodic activity [57, 58]. Grigoleit and Grigoleit performed a meta-analysis of sixteen placebo-controlled clinical trials studying the use of enteric-coated peppermint oil capsules to treat IBS, and found that the overall success rate of peppermint oil capsules was 58% compared to 29% for placebo . They concluded that “peppermint oil…may the drug of first choice in IBS patients with non-serious constipation or diarrhoea to alleviate general symptoms and to improve quality of life e.g. pain or bloating”. A recent meta-analysis of four clinical trials confirmed this view . In fact peppermint oil, in the form of a preparation called Peppermint water BP1973, has long been used to treat dyspepsia, flatulence and stomach cramps, and has just been awarded a traditional herbal registration certificate . Another herbal preparation that has shown promise in the treatment of IBS is Iberogast® (also called STW-5), a liquid formulation of nine different herbs, namely bitter candytuft, or clown’s mustard plant (Iberis amara), German chamomile (Matricaria recutita) flowers, angelica (Angelica archangelica) root, caraway (Carum carvi) fruit, lemon balm (Melissa officinalis) leaves, greater celandine (Chelidonium majus) aerial parts, liquorice (Glycyrrhiza glabra) root, milk thistle (Silybum marianum L) and peppermint oil . In a randomised, double-blind, placebo-controlled trial, STW 5 (Iberogast®) reduced abdominal pain, problems with bowel habit and flatulence in IBS patients . Iberogast® is also effective against functional dyspepsia  and is widely prescribed in Germany with more than a million prescriptions being written for it in Germany in 2002 . Iberogast® has been shown to have antispasmodic, anti-inflammatory and antioxidant activity, and also acts as a secretagogue (reviewed in [55, 62]). A similar mixed herbal extract, called carmint, which consists of herbal extracts of lemon balm, spearmint (Mentha spicata) and coriander (Coriandrum sativum), reduced abdominal pain and bloating in IBS patients in a clinical trial . IBS-D patients were prescribed loperamide, and IBS-C patients were prescribed psyllium, plus either carmint or placebo; there was a significant reduction in symptoms in the IBS patients taking carmint compared to those taking the placebo after eight weeks.
Herbs have traditionally been used to treat bacterial infections , for instance lavender (Lavandula angustifolia) oil and tincture were used to treat wounds before the First World War. Many culinary herbs have been reported to possess antibacterial properties [67, 68], as have the essential oils of these herbs . Many herbs, for instance fennel (Foeniculum vulgare), lavender, peppermint, rosemary (Rosmarinus officinalis) and sage (Salvia officinalis), have been used traditionally as digestives, aiding digestion or reducing flatulence [67, 68, 70]. Our hypothesis is that the digestive properties of a particular herb may be linked, at least in part, to the herb’s antibacterial action. Essential oils and herbal extracts have an advantage over conventional antibiotics since they may contain several antibacterial compounds that act in different ways, so that it would be more difficult for bacteria to develop resistance. For instance lemon grass (Cymbopogon citratus) essential oil contains at least sixteen compounds  and successfully inhibited the growth of Helicobacter pylori over many bacterial generations, whereas antibiotic resistant H. pylori emerged after ten passages on plates containing only the antibiotic clarithromycin .
NICE guidelines recommend that further research should be conducted to study the possibility of using herbal medicines to treat IBS. With this in mind, in order to increase our understanding of the mechanism of action of herbal medicines that have been shown to be beneficial in treating IBS, and to identify other essential oils or extracts that would be useful candidates for clinical trials, we have conducted a preliminary study in vitro using a non-pathological strain of E. coli. We have compared the antibacterial activity of essential oils of a range of herbs that have been used traditionally as digestives, in three separate assays. We found that the essential oils with the most potent antibacterial activity in the three assays were those of coriander seed, lemon balm and peppermint. Interestingly, essential oils or extracts of coriander, lemon balm and peppermint are all present in herbal medicines that have been validated for use in the treatment of IBS by at least one clinical trial (without their mechanism of action being ascribed to an antibacterial effect). We identified the compounds present in the coriander seed, lemon balm and peppermint essential oils that we had used, by thermal desorption gas chromatography mass spectrometry. Finally we tested the antibacterial activity of extracts of coriander, lemon balm and spearmint leaves that had been made with various solvents to determine whether ethanolic tinctures of these herbs (which have been used instead of essential oils in some of the IBS medicines) would have antibacterial activity. This has allowed us to propose a new mechanism of action for these herbal medicines, and suggest some other herbs/essential oils that could be tested in further clinical trials.