1. Introduction

Irritable bowel syndrome (IBS) is a gastrointenstinal (GI) disorder characterized by altered bowel habits in association with abdominal discomfort or pain in the absence of detectable structural and biochemical abnormalities. [1] Irritable bowel syndrome (IBS) is a common, often debilitating, gastrointenstinal disorder with a worldwide prevalence rate of 10%-20%. [2] The diagnosis of IBS is based on the symptom-based classification system known as the Rome criteria. [3] The diagnostic criteria the changes have included the Rome I criteria, which were revised to the Rome II guidelines. [5] and now to the most recent Rome III criteria to allow for ease of diagnosis. The Rome III diagnostic criteria simply state that a patient must have recurrent abdominal pain or discomfort at least 3d/month in the last 3 months and there is improvement with defecation, associated with a change in stool frequency or onset associated with a change in stool consistency. [4] According to Rome IV diagnostic criteria there should be Recurrent abdominal pain on average at least 1 day/week in the last 3 months, associated with two or more of the criteria related to defecation, associated with a change in the frequency of stool and change in the appearance of the stool. [5] According to WHO DMS-IV code classification for IBS and its subcategories, IBS can be classified as either diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), or with alternating stool pattern (IBS-A) or pain-predominant. In some individuals, IBS may have an acute onset and develop after an infectious illness characterized by two or more of the following: fever, vomiting, diarrhea, or positive stool culture. This post-infective syndrome has consequently been termed “postinfectious IBS” (IBS-PI) [5] IBS is a remarkably common condition according to population-based studies. [6,7,8] IBS has been conceptualized as condition of visceral hypersensitivity(leading to abdominal discomfort or pain) and gastrointenstinal motor disturbances(leading to diarrhea or constipation) [9,7] There is increasing evidence regarding the role of immune activation in the etiology of IBS, which has mainly been shown in studies investigating mechanisms of IBS [10] Exposure to intenstinal infection induces persistent low grade systemic and mucosal inflammation, which is characterized by an altered population of circulating cells, mucosal infiltration of immune cells and increased production of various cytokines in IBS patients. Recent studies have also indicated an increased innate immune response in these patients by evaluating expression and activation of Toll-like receptors. [11] Additional studies are necessary to understand the precise mechanism of immune activation and its relationship to the development of IBS. [12] Small intenstinal bacterial overgrowth (SIBO) is prevalent in IBS, it remains unclear whether SIBO causes IBS. [13] Serotonin (5-HT) acting particularly through the 5-HT3 and 5-HT4 receptors, plays a significant role in control of gastrointenstinal motility, sensation and secretion. [14,15,16] Bristol Stool Form Scale (BSFS) described seven types of stool: Type 1 to Type 7. Stool Type 1 and 2 is being associated with constipation, while stool types 6 and 7 were associated with diarrhea. The BSFS is a convenient way for patients to describe their bowel habits. In addition, at the two extremes (Bristol stool type 1 and 2 or types 6 and 7) the stool form serves as a rough surrogate marker of colon transit. [17] Toll-like receptors (TLR) are membrane-bound receptors that recognize and bind microbial components in the GI mucosa, leading to an inflammatory response. [18] Expression levels of TLR-4 and TRL-5 genes in biopsy samples from the sigmoid colon of patients with IBS were 1-8 fold higher in comparable to healthy individuals. As well TLR-4 and TLR-5 protein levels in colonic crypts and the luminal surface were 4-6 fold greater, in patients with IBS-D compared with healthy individuals and TLR-4 gene expression levels correlated with stool frequency in patients with IBS. [19] Gastrointenstinal immune activation may be linked to visceral hypersensitivity and activated Immune cells localized near enteric nerves. [20] Visceral hypersensitivity (i.e altered pain perception to normal physiologic stimulation) is increased in patients with IBS compared with healthy individuals, and approximately half of patients with IBS exhibit hypersensitivity to rectal distension. [21,22,23] Alteration in the gut microbiota are thought to be involved in the pathophysiology of IBS. Indeed the gut microbiota is altered in patients with IBS in compared to healthy individuals. [24] There is no biological marker to explain the different symptoms of IBS. The majority of patients with IBS also have significant bloating and gas as part of their presentation, in addition to a degree of constipation, diarrhea and pain. [25] Rifaximin is a rifamycin antimicrobial agent, a rifampin structural analog. [26] Rifaximin inhibits RNA synthesis by binding to the β subunit of bacterial DNA-dependent RNA polymerase. [27] The addition of a pyridoimidazole ring to the rifampin molecule makes rifaximin a largely water-insoluble, poorly absorbable antibiotic, hence associated with few systemic adverse events. [28,29] Although its poor GI absorbability leads to low systemic blood levels, fecal concentration remains elevated with unchanged drug. [24] The increased solubility of rifaximin in bile leads to higher luminal concentrations and enhanced antimicrobial effects. [30] ACG guidelines currently recommended against the use of the antidiarrheal agent loperamide for use of the antidiarrheal agent loperamide for overall symptom improvement in patients with IBS. [31] For diarrhea-predominant IBS, 2 to 4 mg of loperamide up to four times a day can be effective. [32] Loperamide slows intenstinal transit, increases intenstinal water absorption, and increases intenstinal Water absorption. Loperamide is preferred to other opioid agents because it does not cross the blood brain barrier. Hence in this study the treatment outcome is compared between antibiotic (Rifaximin) and antidiarrheal (Loperamide) in patients diagnosed as IBS-D according to Rome IV diagnostic criteria.

2. Materials & Methods

The study was conducted in Apollo Hospital Bhubaneswar in the department of Gastroenterology between the period of April 2021 to June 2021. Total 100 patients were included in the study. All the patients were diagnosed as IBS-D according to Rome IV criteria.50 patients were in Group A and 50 patients were in Group B. Group A patients were given Rifaximin 1200 per day and Group B patients were given 2 mg Loperamide thrice daily for 14 days. All patients were assessed after one month and three months of drug administration. Patients were assessed by parameters like Pain Abdomen, Stool frequency, Abdominal Bloating and Sense of urgency of Stool.

Inclusion criterias:

1. Patient Diagnosed with IBS with Diarrhoea (IBS-D) according to Rome IV criteria between the age 18 to 50 (Both male and female)

2. Patient with History of wt loss

3. Pain associated with loose or more frequent stool

Exclusion criterias:

1. Lactose malabsorption

2. Women with pregnancy and breast feeding

3. Patients below 18yrs or above 60yrs of age

4. Irritable Bowel Disease (Chron’s disease & UC)

5. Diarrhea caused by antibiotic medication

6. Diarrhea caused by severe bacterial infection

Study Design:

This study is a Prospective Clinical study. It was conducted for a period of 3 months. Total 100 patients were included in the study and divided in to two groups containg 50 patients each. The patients were diagnosed as IBS according to Rome IV diagnostic criteria. Patients with Group A & B were treated with Rifaximin and Loperamide for 14 days respectively. All patients were assessed basing upon the different diagnostic parameters. Patients were assessed at 0, 1 and 3 months intervals.

Statistical Analysis:

All datas were analysed using Chi-square Test. p<0.05 considered as statistically significant and p<0.001 as highly significant.

3. Results

Result of both Group A and Group B were compared basing upon the diagnostic criterias like Pain abdomen, stool frequency/day, abdominal bloating and sense of Urgency of stool.

Table 1. Group: A (50 patients) Patients treated with Rifaximin 1200mg/day for 2 weeks and were assessed at the starting of treatment, after 1 month and 3 months of Rifaximin treatment (Represented in no of Patients)

Table 2. Group: B (50 patients) Patients treated with Loperamide 2mg TDS for 2 weeks and were assessed at the starting of treatment, after 1 month and 3 months of Loperamide treatment (Represented in no of Patients)

Graph 1. Comparision of Different diagnostic parameters after 1&3 months of the study in Group: A (Represented in no)

Graph 2. Comparision of Different diagnostic Parameters after 1&3 months of the study in Group: B (Represented in no)

Table 3. Assessment of Bristol Stool Scale Score and Abdominal Pain between Group A and Group B after one month (Represented in no of Patients)

Table 4. Assessment of Bristol Stool Scale Score and Abdominal Pain between Group A and Group B after 3 month (Represented in no of Patients)

Graph 3. Comparision of Frequency of Pain Abdomen and Bristol Stool Scale Score after one month between Group A and Group B

Graph 4. Comparision of Frequency of Pain Abdomen and Bristol Stool Scale Score after 3 months between Group A and Group B (Represented in no)

It is observed from the table 1 that pain abdomen, stool, frequency, abdominal bloating and sense of urgency is significantly reduced after 3 months of Rifaximin treatment. It is also observed from the table 2 that there is also improvement of diagnostic parameter with Loperamide treatment after 1 & 3 months but it was less in comparision to Group A. From Graph 1 & 2 it observed that there is more improvement in different diagnostic parameters after 1 and 3 months in Group A as compared to Group B. Table 4 shows that out of 50 patients in group B 35 patients were found with Bristol Stool Scale Score <5 and 47 patients were found with Bristol Stool Scale Score < 5 in Group A after 3 months. Again in table 3 & 4 it is seen that no of patients showing improvement in BSSS<5 is less in no in Group B as Compared to Group A. The findings of table 3 & 4 are graphically well represented in Graph 3 & 4. Also graph 3 & 4 shows there is improvement in pain frequency in patients with Group A after 1 & 3 months.

4. Discussion

The pathophysiology of IBS is multifactorial in nature, with interplay among several factors. SIBO is more prevelant in patients with IBS versus healthy individuals and was associated with specific demographic and disease characteristics (e.g female sex, IBS-D). IBS management has been primarily focused on symptomatic treatment until data revealed that patient suffering from IBS might have alterations in the gastrointenstinal flora, manifested by excessive bacteria in the small bowel, known as bacterial over growth. [33] Rifaximin improved GI mucosal inflammation i.e decreased levels of IL-6, IL-17 and TNF-α genes and normalized visceral hypersensitivity following a decrease in concentration of ileal bacteria.

[34] Loperamide is effective for the treatment of acute diarrhea but not for abdominal pain and bloating which is often considered to be most bothersome IBS symptoms. [35] Rifaximin shows a lower degree of resistance compared to rifampin possibly because of high gut concentrations and extremely low systemic absorption. [36]

5. Conclusions

Keeping in view of increasing the prevalence of IBS in general population this study is conducted in a tertiary care hospital. The findings of the study suggests that all the diagnostic parameters are improved in treatment with Rifaximin in comparision to Loperamide both after 1 month and 3 months of observation. The no of patients showing improvement in Bristol Stool Scale Score is more Rifaximin treated patients. It can be concluded from this study that treatment with antibiotic Rifaximin shows significant improvement in symptoms of Irritable Bowel Syndrome with diarrhea in comparision to antidiarrheal Loperamide. Hence Rifaximin a broad spectrum poorly absorbed oral antibiotic having more efficacy than Loperamide in treatment of IBS-D with added up advantages like excellent safety profile and limited cross-resistance with other antimicrobials.