Introduction

Irritable bowel syndrome (IBS) is characterized by a combination of abdominal pain, bloating, and stool irregularity [1]. Many patients are dissatisfied with the pharmacological treatment of IBS and turn to “complementary and alternative medicine" (CAM). In particular, plant-based preparations to treat abdominal symptoms are popular [2-4].

Aims & Methods

A systematic review and meta-analysis to present the current evidence on phytotherapy for IBS was performed.
A literature search was done using 3 electronic databases (Medline via PubMed, Embase via Ovid, and Web of Science Core Collection) from inception to April 2023. A total of 7894 citations were found. Studies were excluded if they met the following exclusion criteria: (i)were homeopathic medicines, (ii) unpublished or only partially published studies, (iii) patients under 18 years of age, (iv) studies with fewer than ten participants, and (v) publication languages other than German or English. Efficacy was assessed using dichotomous ratings of change in IBS symptoms. To pool data a random effects model with 95% confidence intervals was used. I2 statistics were used to test for heterogeneity of included studies. Scores were 0-24% no-, 25-49% low-, 50-75% moderate- and >75% high heterogeneity.

Results

Through the screening process, 56 eligible studies were identified (6054 patients).
Meta-analysis was performed for fibre (8 studies), peppermint oil (7 studies), aloe vera (3 studies), and Chinese herbal medicine (7 studies). At least one randomized controlled trial (RCT) was performed for the following plant-based products: Ginger, Kiwi fruit, St John’s Wort and Aniseed oil; however, there was insufficient data to perform meta-analysis. For 192 of 387 patients fibre was helpful; whereas, placebo intake was beneficial for 127 of 346 patients (RR=1.22; 95% CI: 1.00-1.49). For 144 of 311 patients peppermint oil improved symptoms; whereas, in the control group, 97 of 357 patients experienced a beneficial effect (RR=1.63; 95% CI: 1.33-2.00). For 62 of 155 patients aloe vera relieved symptoms; whereas, the control intervention was helpful for 51 of 144 patients (RR=1.25; 95% CI: 0.76-2.06). In 403 of 731 patients, Chinese Herbal Medicine therapy had a positive effect; whereas, in the placebo group, 245 of 723 patients found the therapy helpful (RR=1.56; 95% CI: 1.27-1.92. The heterogeneity in the studies ranged from none to moderate. Many studies had some concern of bias in the Risk of Bias 2 (RoB 2) assessment (42/53).

Conclusion

This analysis supports the use of selected plant-based preparations in IBS management. Peppermint oil and Chinese Herbal Medicine preparations demonstrated significant efficacy compared to placebo. Dietary fiber improved stool frequency but had borderline positive effects on IBS scores. The quality of many studies was limited. Additional well-powered RCTs are needed to establish the places of phytotherapy in the management of functional gastrointestinal symptoms.

References

[1] Lacy, B.E., et al., Bowel Disorders. Gastroenterology, 2016. 150(6): p. 1393-1407.e5
[2] Houghton, L.A., et al., Age, Gender, and Women’s Health and the Patient. Gastroenterology, 2016. 150(6): p. 1332-1343.e4.
[3] Deutsch, J.K., J. Levitt, and D.J. Hass, Complementary and Alternative Medicine for Functional Gastrointestinal Disorders. Am J Gastroenterol, 2020. 115(3): p. 350-364.
[4] Drossman, D.A., et al., International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit. J Clin Gastroenterol, 2009. 43(6): p. 541-50.

Introduction

Global rise in primary Helicobacter pylori (H. pylori) antibiotic resistance has led to a decrease in the treatment efficacy. Understanding the rates of clarithromycin resistance in H. pylori management is essential for determining the optimal eradication therapy and achieve successful clinical outcomes.

Aims & Methods

This review aimed to evaluate the prevalence and geographical distribution of H. pylori primary clarithromycin resistance in Europe. Bibliographical searches were performed in PubMed up to March 2024. Selection: Included studies assessing rates of H. pylori primary resistance to clarithromycin with no time restriction. Publications in any language were considered. Studies that focused on children only or non-European countries were excluded.

Results

Overall, 188 studies were included, evaluating 81,458 patients over more than 30 years (1990-2024). In this time span, the mean prevalence of primary H. pylori clarithromycin resistance in Europe was 17%. This rate increased from 7.3% in the period 1990-1999, to 13% in 2000-2009, reaching 26% in 2010-2019; and then reported a decreased rate to 22% in 2020-2024. In almost all European countries, the clarithromycin resistance rate increased over time, reporting the highest rates in Switzerland (67%), Ireland (50%), Israel (44%), Portugal (40%) and Poland (39%) (2010-2019). The prevalence remained stable in recent years in France (decreasing from 21% to 17%), in Spain (around 15%), and in Turkey (decreasing from 28% to 15%). Southern European countries reported higher rates (>15-20%) than in northern countries (<10-15%).

Table 1. Clarithromycin primary resistance prevalence in Europe in the last four decades (1990-2024). Number of patients tested for Clarithromycin: n (positive resistance results)/N (total with H. pylori). NA: not available.

Conclusion

In Europe, overall H. pylori primary clarithromycin resistance was above 15% in the last 30 years. Variability exists between countries, with Southern European and Mediterranean countries showing higher levels of resistance.

References

Bujanda, Luis et al. “Antibiotic Resistance Prevalence and Trends in Patients Infected with Helicobacter pylori in the Period 2013-2020: Results of the European Registry on H. pylori Management (Hp-EuReg).” Antibiotics (Basel, Switzerland). 2021,10(9):1058.
Macías-García, Fernando et al. “High primary antibiotic resistance of Helicobacter Pylori strains isolated from dyspeptic patients: A prevalence cross-sectional study in Spain.” Helicobacter. 2017,22(6):10.1111/hel.12440.
Tamayo, Esther et al. “Clarithromycin resistance in Helicobacter pylori and its molecular determinants in Northern Spain, 2013-2015.” Journal of global antimicrobial resistance. 2017,9:43-46.
Saracino, Ilaria Maria et al. “Trends in Primary Antibiotic Resistance in H. pylori Strains Isolated in Italy between 2009 and 2019.” Antibiotics (Basel, Switzerland). 2020,9(1):26.
Megraud, Francis et al. “Helicobacter pylori resistance to antibiotics in Europe in 2018 and its relationship to antibiotic consumption in the community.” Gut. 2021,70(10):1815-1822.

Introduction

Prevention of gastric cancer, both primary and secondary, is an extremely important component of the management of patients infected with Helicobacter pylori. An important component of secondary prevention of gastric cancer is the use of gastroprotectors and repair stimulants, in particular the alpha-glutamil-triptophan, especially in people with a potentially precancerous condition – chronic atrophic gastritis

Aims & Methods

The aim: to estimate the effectiveness of the alpha-glutamyl-tryptophan as a local cytoprotector for gastric mucosa cells in patients with chronic atrophic gastritis (CAG).
Materials and methods: 116 patients with H. pylori-associated CAG took two treatment lines: 1. standard eradication therapy 10 days, 2. alpha-glutamyl-tryptophan(58 patients)/placebo(58 patients) 28 days. For all patients before and after treatment we performed gastroscopy with two biopsies from atrophic area, histological study of these biopsies, daily pH-metry and Gastropanel.

Results

Alpha-glutamyl-tryptophan in comparison with placebo have statistically significant: regenerative effect (26.1% increase in the number of glands per 1 mm² of the gastric mucosa (GM) by histological study) and anti-inflammatory effect (decrease of GM edema and hyperemia by endoscopy data, reduction of the number of inflammatory infiltration cells per 1 mm² of GM: eosinophilic granulocytes – 3 times, neutrophilic leukocytes – 4 times, macrophages – 1.5 times, lymphocytes – 28.2%, plasmocytes – 29.6% by histological study). Also alpha-glutamyl-triptaphan improved the functional posibilities of stomach: a decrease in the level of gastrin-17 (p = 0.005) and an increase in the value of the PG I/PG II ratio (p=0.003), there was a shift in the acidic side of the pH values (p=0.001) when comparing indicators before and after treatment. There were no statistically significant changes in these parameters in the placebo group. According to the results of gastroscopy, a statistically significant decrease in the severity of edema of the gastric mucosa (p=0.008), the total set of signs of an acute inflammatory process (p=0.006), and a decrease in the proportion of outcomes with negative dynamics of the inflammatory process (p=0.038) were revealed in alpha-glutamyl-tryptophan group.

Conclusion

Alpha-glutamyl-tryptophan can be recommended for local cytoprotection in CAG, espessially fpr H. pylori associated gastritis for prevention the progression of atrophy and inflammation, and also lowering the risk of gastric cancer.

Disclosure

nothing to disclose

Clinical Case Summary

A 22-years-old woman was admitted to our hospital with diarrhea, abdominal pain, vomiting and weight loss for the last 3 months. She was previously treated with hydroxychloroquine and steroids because of symmetrical polyarthralgia with positive antinuclear antibody and anti-double stranded DNA antibody, but she voluntarily abandoned such treatment.
Laboratory results revealed severe protein-calorie malnutrition, hypoalbuminemia, hypocomplementemia and hypertransaminasemia. Stool cultures, faecal calprotectin and ileocolonoscopy were normal. We performed an abdominal and a small bowel ultrasound which demonstrated hepatomegaly, ascites, abdominal lymphadenopathy and a pronounced submucosal edema of the gut, with normal bowel wall stratification. Gastroscopy showed thickened gastric folds, mucosal erythema and the histological and microbiological study of the samples ruled out coeliac and Whipple's diseases, and mycobacterium infection. Thoracoabdominal computed tomography showed thickened gastric - small and large - bowel wall with hypervascularity of the mesentery with vascular dilation (“comb sign”) and bilateral ureterohydronephrosis.
Systemic lupus erythematosus flare with gastrointestinal, hepatic and genitourinary affection was suspected. We referred the patient to the Autoimmune Disease Department where hydroxychloroquine and intravenous steroids were started with progressive symptomatic improvement.
Lupus enteritis is an uncommon manifestation caused by the creation of immune complexes against small vessels of the gut, mainly the small bowel, with a challenging diagnosis and poor outcome. Image findings are basic for diagnosis, and in this particular case, the intestinal ultrasound was the key for guiding the differential diagnosis. We rarely found alterations with endoscopic samples, but they are useful to exclude other diseases. A multidisciplinary management is essential for generating an adequate diagnosis and treatment of these types of patients.

References

Image 1: Intestinal ultrasound: image showing gastric antrum with submucosal edema affecting the stomach diffusely with a thick wall (7.5 mm).
Image 2: Intestinal ultrasound: edematous small intestine Kerckring valves and ascites between bowel loops.
Image 3: Upper endoscopy. Edematous gastric mucosa with thickened gastric folds and scarce distensibility.

Introduction

Irritable Bowel Syndrome (IBS) is a chronic disorder of the gut-brain interaction characterized by visceral hypersensitivity. There is growing evidence underscoring the beneficial impact of probiotics and postbiotics with psychobiotics properties in relieving stress-related gastrointestinal disorders in humans especially in patients suffering from IBS. We have previously shown that high GABA-producer L. lactis CNCM I-5388 exerts antinociceptive properties after 5- and 10-days oral treatment in an IBS-like rat model. We demonstrated, using both mutant L. lactis ΔgadB strains and GABA_B receptor antagonist that these antinociceptive properties were dependent on the GAD-enzymatic activity of L. lactis and mediated by host’s GABA_B receptors. In addition, we have shown that CNCM I-5388 displayed a high cell-bound GAD activity and survival in vitro under HCl-mediated acidic stress.

Aims & Methods

In this work, we were interested in studying the GABA-producer L. lactis CNCM I-5388 as an active-enzyme postbiotic to relieve visceral hypersensitivity mediated by a psychological stress.
L.lactis CNCM I-5388 was inactivated by ethanol (EtOH) while maintaining its GAD activity. Female Wistar rats were treated orally for 1, 5 or 10 days by the EtOH-treated nonviable L.lactis CNCM I-5388 form or the viable L. lactis CNCM I-5388 or vehicle. Visceral sensitivity in response to colorectal distension was measured by electromyography before and after partial restraint stress (PRS). GABA levels were quantified by HPLC both in the stomach collected from rats and in the gastric compartment of the TIM-1 human gut model in fed state.

Results

A daily treatment for 5 and 10 days by L. lactis CNCM I-5388 both in its viable and nonviable forms counteracted visceral hypersensitivity-induced by PRS in response to colorectal distension. However, after a single administration only viable L. lactis CNCM I-5388 tended to reduce visceral hypersensitivity. After 5-days treatment, the production of GABA within the stomach was enhanced in stressed rats treated with the viable or nonviable L. lactis CNCM I-5388 form. This increase was confirmed by using the TIM-1 human gut model.

Conclusion

Our results highlight that a postbiotic with an active-GAD of L. lactis CNCM I-5388, similarly to its viable psychobiotic form, exerts visceral antinociceptive properties in an IBS-like rat model. These effects are associated with GABA production in the stomach where the low pH promotes GAD activity. From a clinical point of view, this “active GAD-bag” concept offers a new therapeutic perspective in the management of visceral pain in IBS patients with a superior safety profile compared with GABA-producing pyschobiotics that could acquire antibiotic resistance and virulence factors in chronic use.

Disclosure

Jonna Koper, Elyse Parent, Nabil Bosco, Nathalie Ballet and Sophie Legrain-Raspaud are full-time employees of Lesaffre. None of the authors have a conflict of interest.

Introduction

Chronic constipation is a prevalent gastrointestinal complaint with increasing incidence among the aging population. Examining colonoscopy performance in chronic constipation across age groups, this study aims to comprehensively assess diagnostic yield and compare results with average-risk controls.

Aims & Methods

A retrospective analysis was conducted on 50,578 colonoscopy procedures performed over 12 years, including 5,478 constipated patients. An average-risk control group (n=4,100) was included. Data extracted from electronic medical records covered demographics, operational aspects, and colonoscopy findings. The primary outcome measures included the diagnosis rate of colorectal cancer (CRC), polyp detection rate (PDR) and inflammatory bowel disease (IBD) diagnoses in constipated patients versus controls, with age-based and multivariate analyses.

Results

Constipated patients exhibited lower rates of adequate bowel preparation (92.7% vs. 85.3%; p < 0.001) and a lower cecal intubation rate. No significant variances between CRC and PDR were observed between constipated and controls, except for a potential of a slightly elevated CRC risk in constipated patients older than 80 (2.50% vs. 0% in controls; p = 0.07). However, multivariate analysis demonstrated that constipation did not confer an increased risk for CRC or polyp detection across all age groups. Notably, younger constipated patients exhibited a higher rate of IBD diagnoses (1.7% vs. 0.1% in controls; p < 0.001).

Conclusion

Conclusion: Constipation did not confer an increased risk for CRC or polyps among all age groups, except for a potential signal of elevated CRC risk in patients older than 80, and was associated with higher rates of IBD in younger patients.

References

1. Aziz I, Whitehead WE, Palsson OS, Törnblom H, Simrén M. An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation. Expert Rev Gastroenterol Hepatol. 2020 Jan;14(1):39-46.
2. Camilleri M, Brandler J. Refractory Constipation: How to Evaluate and Treat. Gastroenterol Clin North Am. 2020 Sep;49(3):623-642.
3. Shahini E, Sinagra E, Vitello A, Ranaldo R, Contaldo A, Facciorusso A, Maida M. Factors affecting the quality of bowel preparation for colonoscopy in hard-to-prepare patients: Evidence from the literature. World J Gastroenterol. 2023 Mar 21;29(11):1685-1707.
4. Mahmood S, Farooqui SM, Madhoun MF. Predictors of inadequate bowel preparation for colonoscopy: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2018;30:819–826.
5. Hassan C, East J, Radaelli F, Spada C, Benamouzig R, Bisschops R, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy. 2019 Aug;51(8):775-794.
6. Włodarczyk J, Waśniewska A, Fichna J, Dziki A, Dziki Ł, Włodarczyk M. Current Overview on Clinical Management of Chronic Constipation. J Clin Med. 2021 Apr 16;10(8):1738.
7. James SL, van Langenberg DR, Taylor KM, Gibson PR. Characterization of ulcerative colitis-associated constipation syndrome (proximal constipation). JGH Open. 2018 Aug 5;2(5):217-222.