Factors associated with irritable bowel syndrome and Helicobacter pylori infection: public knowledge and awareness of signs and symptoms

Abstract

Objective

To investigate factors related to the risk of developing irritable bowel syndrome (IBS) or Helicobacter pylori infection.

Methods

This cross-sectional, questionnaire-based study analysed the responses from participants that completed an online questionnaire, which asked about their knowledge of the causes and risk factors associated with IBS and H. pylori infection.

Results

The study analysed responses from 230 participants: 181 females (of 227 participants; 79.7%) and 190 aged 18–40 years (of 228; 83.3%). Of the 230 participants, 40 (17.4%) had been diagnosed by a physician with IBS and 57 (24.8%) had been diagnosed with H. pylori infection. Of 226 participants, 93 (41.2%) had self-medicated with antibiotics in the past 6 months for various reasons. The overall mean ± SD knowledge score about IBS and H. pylori infection for the study cohort (n = 230) was 35.8 ± 19.2%. Wald χ²-test analysis demonstrated that chronic diseases, antibiotic use and having an endoscopy were significantly associated with developing IBS. Male sex and chronic diseases were significantly associated with H. pylori infection. Logistic regression analysis showed no relationship between IBS and H. Pylori infection.

Conclusion

Chronic diseases was the only risk factor common for IBS and H. pylori infection.

Introduction

Functional gastrointestinal disorders are a group of chronic disorders of multifactorial aetiologies attributed to abnormalities in the stomach–gut–brain interaction and defined by symptom-based criteria. ¹ These conditions are very common, such as irritable bowel syndrome (IBS), and they can considerably reduce individual quality of life and work productivity. For example, in Palestine, IBS affects 30% of the population and it is the most frequent reason why patients visit gastroenterology clinics; ² and it is considered a significant socioeconomic burden to society. ³ Despite the global prevalence of IBS, its pathophysiology remains unclear. However, disturbances in gut microbiota and persistent, subclinical systemic and mucosal inflammation in individuals with IBS has been reported. ⁴ One study found significant overlaps between patients with IBS and those with dyspepsia. ⁵

Helicobacter pylori is a microaerophilic Gram-negative spiral bacterium that is helix shaped and motile even in highly viscous mucus layers, which are properties that might allow this organism to evade both gastric motility and peristalsis, and to some extent gastric acidity. In addition to weakening the gastric mucosal barrier, which permits back-diffusion of hydrogen ions, resulting in further tissue injury, there are also local immune responses to the organism. ⁶ H. pylori might adhere to the gastric mucosa through specific adhesion mechanisms, which might lead to chronic severe gastrointestinal tract (GIT) diseases. ⁷ H. pylori has been shown to be an important player in IBS and other gastrointestinal conditions. What determines the severity of the condition is a combination of genetic predisposition of the host, virulence factors of certain species of the H. pylori (e.g. cytotoxin-associated gene [Cag] A and CagB proteins), mechanical damage to the mucosa and alterations of gastric and duodenal secretions. ⁸ Strains of H. pylori that produce CagA protein cause chronic inflammation in the stomach and duodenum, and microbial dysbiosis. ⁹ A study has linked H. pylori infection, especially CagA strains, to dyspepsia, hyperemesis gravidarum, ¹⁰ active gastritis and even mucosal cell membrane damage.

Helicobacter pylori infection can cause systemic inflammation and altered microbiome diversity. This in turn perpetuates a cycle of chronic, low-grade, subclinical inflammation. Apart from mucosal inflammation, neuro-inflammation, via the gut–brain axis, is probably involved in the pathophysiology of IBS. This might result in altered neuroendocrine pathways and glucocorticoid receptor genes (hypothalamic–pituitary–adrenal axis and serotonergic [5-hydroxytryptamine] functioning), which could in part, account for the symptoms of IBS. ¹¹ Some studies have highlighted increased rates of H. pylori infection in patients with IBS and other studies have disputed this observation.^12–14

Other factors that have been studied that might have a significant impact on IBS are smoking, source of water, sex, hormonal changes, use of oral contraceptive pills or gonadotropin releasing hormone agonists, sleep duration, lifestyle, antibiotic use, chronic diseases and diet.^15–31

In theory, chronic H. pylori infection could be involved in the pathogenesis of IBS by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material. Similar mechanisms may also be responsible for the co-existence of IBS with other extraintestinal manifestations other than H. pylori such as amoeboid and giardiasis.

This current study investigated a range of factors including lifestyle, eating habits, signs and symptoms of concern for both IBS and H. pylori infection in a Palestinian community in order to determine if there were common backgrounds for both conditions.

Patients and methods

Study design and patient population

This cross-sectional, questionnaire-based study used a previously standardized questionnaires,^32,33 which was slightly modified and adapted to suit Palestinian cases of IBS and H. pylori infection. The questionnaire was posted online at the university website, Hebron pharmacy group, every city web page (Nablus, Bethlehem, Hebron, Ramallah city, Tulkarm, Jericho, Qalqilia, Jenin and Gaza) and on the Facebook pages of the coauthor graduate students in addition to their friends’ and relatives’ networks by the Department of Clinical Pharmacy and Practice, Faculty of Pharmacy and Medical Sciences, Hebron University, Hebron, West Bank, Palestine between February 2022 and March 2022. Inclusion criteria were as follows: (i) aged ≥18 years; (ii) first 300 responses to the questionnaire; (iii) diagnosed with or had some GIT symptoms (e.g. constant burping [gas], crackling sounds in the intestines, vomiting and nausea, constant constipation and/or diarrhoea, being affected by specific types of food (chili, spices), sudden abdominal pain when exposed to a stressful situation). Exclusion criteria were as follows: (i) colorectal carcinoma; (ii) stomach resection or bypass surgery or gastric cancer; (iii) Crohn’s disease or any other genetic or familial GIT conditions.

Study participants had to agree online to the conditions and terms of the study. They provided digital consent before they logged onto the form and they were enrolled consecutively to the study. The study guaranteed their rights as volunteers participating in this study and they retained the right to withdraw at any stage of the study. All participant details were de-identified to ensure confidentiality of all participants at all times. The study was approved by the Internal Review Board of Hebron University, Hebron, West Bank, Palestine. This study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. ³⁴

Questionnaire

The questionnaire contained 60 questions in total and had sections that covered the following factors: (i) sociodemographic characteristics; (ii) family history of GIT problems; (iii) health status (hypertension, diabetes mellitus and hyperlipidaemia); (iv) medical history (previous gastroscopy); (v) medications taken in the past 6 months (particularly the use of proton pump inhibitors and antibiotics). Participants were also asked about their lifestyle including living conditions, smoking, diet, exercise, sleep and other personal habits. A special section included questions about their knowledge of H. pylori and IBS symptoms; 25 questions covered their likelihood of having IBS and 19 questions related to the possibility of H. pylori infection and transmission. The last section contained six questions about the effect of hormones or oral contraceptive use on IBS development in married women.

Statistical analyses

All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA). Data are presented as n of patients (%). Logistic regression models were used to analyse data. Wald χ²-test was used. A P-value <0.05 was considered statistically significant.

Results

This cross-sectional, questionnaire-based study analysed the data from 230 participants that completed the online questionnaire. Table 1 presents the details of the sociodemographic characteristics and clinical data of the participants. There were 181 females (of 227 participants; 79.7%). The majority of the participants were aged 18–40 years (190 of 228; 83.3%). Of the 230 participants, 40 (17.4%) had been diagnosed by a physician with IBS and 57 (24.8%) had been diagnosed with H. pylori infection. Of 226 participants, 93 (41.2%) had self-medicated with antibiotics in the past 6 months for various reasons.

Table 1.

Sociodemographic and clinical characteristics of study participants (n = 230) that completed an online questionnaire about irritable bowel syndrome and Helicobacter pylori infection.

Characteristic	Categories	n a	%
Age categories, years	18–40	190	83.3
	41–60	36	15.8
	>60	2	0.9
Sex	Female	181	79.7
	Male	46	20.3
Education level	Primary school	38	16.7
	Diploma	24	10.6
	Bachelor’s degree level	151	66.5
	Postgraduate	14	6.2
Family history	Yes	26	24.3
	No	39	36.4
	Not known	42	39.3
Job	Student	78	34.2
	Employee	52	22.8
	Do not work	60	26.3
	Other	17	7.5
	Work in medical field	21	9.2
Chronic diseases	No	176	77.5
	Yes	51	22.5
Weight loss	No	125	54.8
	Yes	103	45.2
Residencial area	City	108	47.6
	Village	79	34.8
	Camp	11	4.8
	Town	29	12.8
Self-use of antibiotics	No	133	58.8
	Yes	93	41.2
Endoscopy	No	198	87.6
	Yes	28	12.4
Sleep duration, h	<6	38	16.7
	6–8	172	75.4
	>8	18	7.9
H. pylori diagnosis	Yes	57	24.8
	No	173	75.2
Irritable bowel syndrome diagnosis	Yes	40	17.4
	No	190	82.6

^aThe total number of respondents varied for the different characteristics according to the number that answered the question.

The questionnaire assessed the knowledge of the study participants about key aspects of IBS and H. pylori as related to IBS (Table 2). The overall mean ± SD knowledge score about IBS and H. pylori infection for the study cohort (n = 230) was low at 35.8 ± 19.2% (data not shown). The Wald χ²-test was used to determine which factor(s) were most likely to affect the probability of getting IBS (Table 3). The results of this analysis demonstrated that chronic diseases, antibiotic use and having an endoscopy were significantly associated with the probability of getting IBS (P = 0.018, P = 0.033 and P = 0.032, respectively). The Wald χ²-test was also used to determine which factor(s) were most likely to affect the probability of getting H. pylori infection (Table 4). The results of this analysis demonstrated that male sex and chronic diseases were significantly related to H. pylori infection (P = 0.043 and P = 0.014, respectively).

Table 2.

Knowledge about lifestyle practices, foods, medications and other risk factors for irritable bowel syndrome (IBS) of study participants (n = 230) that completed an online questionnaire about IBS and Helicobacter pylori infection.

Question	Possible answer	Correct (✓)/incorrect (×)	n	%a
Do you think that milk and dairy products increase the severity of infection for people with H. pylori (one answer)	Yes	✓	97	42.2
	No	×	43	18.7
	May be	×	90	39.1
According to your beliefs, which of the following sentences is correct about IBS (multiple answers)	Drinking stimulants (tea and coffee) or energy drinks frequently reduces risk of IBS	×	191	83.0
	No difference in the severity of these symptoms between a male or female	×	120	52.2
	Irritable bowel syndrome is a chronic and incurable disease	✓	131	57.0
	Endoscopy helps in the correct diagnosis of irritable bowel syndrome	×	99	43.0
	Excessive use of antibiotics does not affect the risk of developing IBS	×	196	85.2
	Males are more likely to have irritable bowel syndrome than females	×	175	76.1
What do you expect the reason for the appearance of symptoms you have? (multiple answers)	Following weight loss diet	✓	135	58.7
	The current psychological status	✓	192	83.5
	Bad eating habits	✓	152	66.1
	Run in the family due to genetics	✓	90	39.1
	Previous gastrointestinal disease	✓	47	20.4
	Excessive intake of antibiotics	✓	51	22.2
	Excessive use of laxatives	✓	46	20.0
	Excessive intake of NSAIDs	✓	25	10.9
The triple treatment of H. pylori is one of the best treatments available. Currently, in your opinion, what is the sufficient treatment period to get rid of this infection? (one answer)	14 days	✓	86	37.4
	1 month	×	48	20.9
	2 months	×	34	14.8
	1 year	×	62	27.0

^aThe percentage values were calculated out of the total number of study participants (n = 230).NSAIDs, nonsteroidal anti-inflammatory drugs.

Table 3.

Analysis of the association between demographic and clinical characteristics and irritable bowel syndrome (IBS) of study participants (n = 230) that completed an online questionnaire about IBS and Helicobacter pylori infection.

Characteristic	B	SE	Wald	Df	P-valuea	Odds ratio	95% CI
							Lower	Upper
Male	−0.87	0.475	3.354	1	NS	0.419	0.165	1.063
Chronic diseases	1.605	0.678	5.611	1	P = 0.018	4.979	1.319	18.793
Weight loss	−0.329	0.425	0.599	1	NS	0.72	0.313	1.655
Antibiotic use	0.959	0.45	4.549	1	P = 0.033	2.61	1.081	6.301
Family history	−0.379	0.443	0.731	1	NS	0.685	0.287	1.632
Sleeping duration, h			1.167	2	NS
<6	−0.219	1.049	0.044	1	NS	0.803	0.103	6.278
6–8	0.452	0.85	0.282	1	NS	1.571	0.297	8.313
Endoscopy	−2.745	1.278	4.613	1	P = 0.032	0.064
Constant	−0.87	0.475	3.354	1	NS	0.419	0.165	1.063

^aWald χ²-test; NS, no significant association between characteristic and IBS (P ≥ 0.05).B, B coefficient; SE, standard error; Wald, Wald χ²-test; Df, degrees of freedom; CI, confidence interval.

Table 4.

Analysis of the association between demographic and clinical characteristics and Helicobacter pylori infection of study participants (n = 230) that completed an online questionnaire about irritable bowel syndrome and H. pylori infection.

Characteristic	B	SE	Wald	Df	P-valuea	Odds ratio	95% CI
							Lower	Upper
Male	−0.985	0.487	4.098	1	P = 0.043	0.373	0.144	0.969
Chronic diseases	1.992	0.811	6.032	1	P = 0.014	7.331	1.495	35.943
Weight loss	−0.294	0.434	0.459	1	NS	0.745	0.318	1.744
Antibiotic use	0.892	0.455	3.835	1	NS	2.439	0.999	5.954
Family history	−0.349	0.448	0.608	1	NS	0.705	0.293	1.697
Sleeping duration, h			0.997	2	NS
<6	−0.212	1.056	0.04	1	NS	0.809	0.102	6.415
6–8	0.418	0.851	0.241	1	NS	1.519	0.287	8.048
Endoscopy	0.202	0.737	0.075	1	NS	1.224	0.289	5.186
Constant	−0.985	0.487	4.098	1	P = 0.043	0.373	0.144	0.969

^aWald χ²-test; NS, no significant association between characteristic and IBS (P ≥ 0.05).B, B coefficient; SE, standard error; Wald, Wald χ²-test; Df, degrees of freedom; CI, confidence interval.

A logistic regression model for the two conditions showed no strong correlation between IBS and H. Pylori infection among the study participants (r = 0.707, P = 0.400; data not shown).

Discussion

This current cross-sectional observational study investigated factors that have an impact on the development of IBS and H. pylori infection with the aim to determine if a causative relationship exists between these two conditions. However, this current study found that there was no causative or chronological relationship between IBS and H. pylori infection. The current study did, however, find that these two conditions had a common risk factor for all patients, which was the presence of chronic diseases.

In this current study, 51 of 227 (22.5%) participants had other concomitant chronic diseases such as diabetes mellitus, hypertension, heart problems or a combination of these conditions for which they were taking regular medications. The relationships between IBS and diabetes mellitus, hypertension or heart problems are well established in literature. The underlying pathophysiology for these relationships has been extensively studied. For example, one of the suggested mechanisms in diabetes mellitus is a reduction in insulin-growth factor I, which may result in smooth muscle atrophy and impaired GIT function. ³⁵ Impaired synthesis of neuronal nitric oxide has been suggested as another mechanism for diabetic enteropathy. ³⁶ Enhanced oxidative stress, autoimmune diathesis and an imbalance between inhibitory and excitatory enteric neuropeptide ratios were also found in patients with diabetes mellitus. ³⁷ A disturbed intestinal microcirculation and cytokine production have been linked to heart failure. ³⁸ Research has linked obesity and metabolic syndrome, well-known risk factors for hypertension or heart diseases, to disturbances of the intestinal microbiota. ³⁹ In addition, significantly lower resting baroreceptor sensitivity among IBS patients and higher blood pressure, compared with healthy control subjects, were attributed to IBS. ⁴⁰ Another study suggested that the decrease in baroreceptor sensitivity determined the severity of IBS through increasing diastolic blood pressure level. ⁴¹

With regard to metabolic syndrome, studies have suggested that IBS might affect the digestion and absorption of fats in the GIT leading to elevated triglycerides, in addition to impaired absorption of mannitol and sorbitol.^42–46 The treatment of IBS and restoring gut microbiota are important measures in preventing metabolic syndrome, which supports the potential link between IBS and metabolic syndrome.^42–46 One common underlying mechanism among all previously mentioned factors is a perturbation of the gut microbiota.

The level of control of chronic diseases in Palestine, especially diabetes mellitus and hypertension, is very poor and that might have had a considerable impact on the prevalence of IBS in the study population. The current study demonstrated that the presence of concomitant chronic diseases was a significant risk factor for both IBS and H. pylori infection. A total of 51 of 227 (22.5%) participants also had chronic diseases in this current study, which supports the idea that chronic diseases are strongly related to IBS and/or H. pylori infection. It should be noted that 93 of 226 (41.2%) study participants used antibiotics and 28 of 226 (12.4%) had undergone endoscopy, both factors that have a considerable negative impact on the gut microbiota. Subtotal gastrectomy (i.e. partial removal of the stomach), anaesthesia and endoscope disinfectant use have been implicated in changes to the gut microbiota composition and H. pylori outbreaks.^47–51

Research has demonstrated that antibiotic use has a negative impact on gut microbiota and leads to loss of colonization resistance against gastrointestinal pathogens such as Clostridium difficile.^52,53 In order to restore gut microbiota, C. difficile infections should be treated using first-line antibiotics such as metronidazole or vancomycin, which further perturb the microbiota. ⁵⁴ It will end up with a vicious cycle of perturbation and restoration of the gut microbiota. Interestingly, the current study observed that 144 of 230 (62.6%) study participants believed they should use triple therapy (amoxicillin, clarithromycin and a proton pump inhibitor [PPI]) for H. pylori infection for periods of 1 month or longer, which is much longer than the recommended course of 14 days. Some practicing physicians prescribe PPIs for 3 months after triple therapy. Some patients continue on a PPI for 1 year or more. All of these practices will either disturb the gut microbiota or lead to a sharp reduction of gut pH. Changes in gut pH lead to H. pylori relapse and further perturbations of the gut microbiota.

Proton pump inhibitors have been associated with IBS by causing small intestinal bacterial overgrowth, which increases with prolonged PPI use and enhances colonic proliferation of C. difficile through microbiota perturbations.^55,56 Although this current study did not have laboratory test results (stool or blood) to prove C. difficile infection in the study participants, their extensive use of antibiotics and the prevalence of concomitant chronic diseases, along with the use of PPI as part of the triple therapy, strongly suggest microbiota perturbation and C. difficile infection among the participants.

This current study also asked study participants about diet and lifestyle in relation to either IBS, H. pylori infection or both. Stress, bad eating habits and following weight loss diets were the top three reasons that participants gave as the causes for their underlying symptoms. Using weight loss diets might be expected in this study cohort because there were high proportions (79.7%) of females and young adults (83.3% were 18–40 years old). Indeed, 135 of 230 (58.7%) study participants thought that dieting might have been the main reason for their symptoms. A total of 192 of 230 (83.5%) study participants reported stress (psychological status in general) as the main reason for their symptoms. A total of 152 of 230 (66.1%) study participants considered bad eating habits as the main reason for their symptoms. When assessing their knowledge about whether frequently drinking stimulants (tea and coffee) or energy drinks reduces the risk of IBS, 191 of 230 (83.0%) answered ‘yes’. In the same context, 133 of 230 (57.8%) study participants answered with ‘may be’ or ‘no’ to the question that asked ‘Do you think that milk and dairy products increase the severity of infection for people with H. pylori’, which it does. In addition, only 51 of 230 (22.2%) study participants thought that their excessive use of antibiotics was the reason for their symptoms. In this current study, 90 of 230 (39.1%) study participants thought that IBS has genetic background and that it runs in their family. Diets with a high fat content and spicy foods are thought to give rise to GIT symptoms. In contrast, diets with low amounts of fermentable oligo-, di- and monosaccharides and polyols have been found to be efficient in alleviating GIT symptoms in IBS patients.^54–56

This current study had several limitations. First, the cross-sectional, questionnaire-based design was limited and a prospective study design to determine a causative relationship between these two conditions would have been better. Secondly, self-reporting about antibiotic use can be inaccurate. Studies that accurately measure the quantity and type of antibiotics used might provide useful information about the impact of the class of antibiotic used, dose and period of use. Thirdly, this study was limited by the fact that the patients did not undergo a physical examination and their medical records were not accessed. The study attempted to determine the risk factors for IBS and/or H. pylori infection as precisely as possible within the limitations of using a self-reported questionnaire. The self-reporting by the study participants of their signs and symptoms might also have been inaccurate and they might have confused their condition with other GIT conditions. It might have also been hard to them to objectively determine the severity of their symptoms. Finally, the largest proportion of participants in the study were young adults, probably because this was an online questionnaire. Only the first 300 responses were recorded due the sample size calculations, but this might not have been a representative sample of the entire population. It is likely that sample bias occurred.

In conclusion, although there was no significant direct causal relationship between IBS and H. pylori infection identified by the current study, their shared common factors support the strict control of concomitant chronic diseases and the limited use of antibiotics in the community. Lifestyle modifications are recommended as potential alternatives to therapeutic modalities for the management and/or prevention of either IBS or H. pylori infection in order to maintain a healthy gut microbiota.