Introduction

The extract of the marshmallow (Althaea officinalis L.) root is used in gastrointestinal complaints involving irritations of the gastrointestinal mucosa [1]. While the underlying mucosa protective and anti-inflammatory effects have been studied thoroughly over the last years, data on ist effect on the gut microbiota are missing.

Aims & Methods

Given that a considerable part of the constituents of the extract can be assumed to be not fully absorbed in the small intestine, its influence on the gut microbiota in the large intestine is worth to be studied.
The impact of marshmallow root extract (STW 42) on the gut microbiome was investigated using the high-throughput, ex vivo SIFR^® technology (Cyptobiotix, Ghent, Belgium). Considering 6 subjects individually, this allowed to cover the broad spectrum of microbial composition that occurs in vivo, in line with the so-called enterotypes, thus ensuring representative findings. Simulating a single intake, Althaea radix (AR) was dosed at 1.875 g/d and inulin (IN; used as positive control) was dosed at equivalent of 2 g/day.

Results

AR impacted microbial metabolite production as was shown by significantly increased total SCFA and significantly decreased pH. While the extent of the effects of IN was larger, nevertheless, AR significantly increased health-related propionate/butyrate generation, suggesting a health-promoting potential of AR. AR showed a specific effect on butyrate production, which suggests a product-specific impact on the human adult gut microbiome.
In contrast to the major interpersonal differences at family and phylum, potent treatment effects were noted at higher phylogenetic resolution (OTU level): AR exerted effects including the consistent stimulation of an OTU related to Ruminiclostridium cellulolyticum.

Conclusion

Overall, the SIFR^® study demonstrated the prebiotic potential of marshmallow root extract (AR) based on the impact on microbial metabolite production and microbial composition. This adds to the evidence supporting its use in functional GI symptoms.

References

1. Committee on Herbal Medicinal Products (HMPC) 2016. European Union herbal monograph on Althaea officinalis L., radix. EMA/HMPC/436679/2015
2. Van den Abbeele P, Deyaert S, Thabuis C, Perreau C, Bajic D, Wintergerst E, Joossens M, Firrman J, Walsh D, Baudot A. Bridging preclinical and clinical gut microbiota research using the ex vivo SIFR^® technology. Front Microbiol. 2023;14:1131662
3. Van den Abbeele P, Grootaert C, Marzorati M, Possemiers S, Verstraete W, Gérard P, Rabot S, Bruneau A, El Aidy S, Derrien M, Zoetendal E, Kleerebezem M, Smidt H, Van de Wiele T. Microbial community development in a dynamic gut model is reproducible, colon region specific, and selective for Bacteroidetes and Clostridium cluster IX. Appl Environ Microbiol. 2010;76:5237-46

Disclosure

PVA, SD, and AB are employees of Cryptobiotix SA, Ghent, Belgium. KB and OK are employees of Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany; AH has obtained project support by Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.

Introduction

Recent evidence suggests that natural products can modulate microbiome composition, offering health benefits. This study evaluates the effects of STW 5 on microbiota in functional dyspepsia (FD) and Irritable Bowel Syndrome (IBS) through a comparison of in vitro and in vivo data.

Aims & Methods

A comprehensive literature review was conducted using PubMed and other scientific databases to collate data on STW 5's impact on the gut microbiome at phyla and genera levels.

Results

In vitro studies demonstrated an increase in Enterococcus and a decrease in Clostridium and Bacteroides [1]. Further in vitro research confirmed an increase in Firmicutes and a reduction in Bacteroidetes, with a decrease of Blautia and Proteobacteria. Unpublished data of the authors indicated increased Bifidobacterium and Blautia, with no change in Lactobacillus [2].
In vivo studies in healthy Wistar rats reported minor increases in the phyla Firmicutes and Bacteroidetes, and a significant decrease in Actinobacteria. Genus-level changes included increases in Bacteroides, Bifidobacterium, and Prevotella, and a significant rise in Methanobrevibacter. In a model of ulcerative colitis, Lactobacillus, Blautia, and Bifidobacterium increased, while Proteobacteria and Enterococcus decreased.[3] In an in vivo model of functional dyspspsia, significant increases were observed for Enterococcus, Lactobacillus, Blautia, and Bacteroidetes. Actinobacteria decreased, with elevated Bifidobacterium compared to FD control, but lower than in healthy controls [4, 5]

Conclusion

The different responses of some genera like Blautia and Enterococcus to STW 5 in in vitro models as compared to in vivo models highlight the complexity of the interactions of the microbiota with STW 5.
The limitations of in vitro models due to the absence of host factors, and the challenges of in vivo models in extrapolating data to humans underscore the advantages of using diverse research methodologies to identify microbial changes relevant to human health.
Our results demonstrate such an approach, revealing consistent microbial shifts across the models. In particular, the upregulation of Bifidobacterium, with the downregulation of Actinobacteria and Proteobacteria, highlight the potential of STW 5 for beneficial gut microbiome modulation, underscoring its multi-target mechanism of action [6].
In conclusion, the presence of different results in different models underscores the need for a multifaceted approach to accurately characterize the intricate interactions between natural products and the gut microbiome.
The identification of consistent microbial shifts associated with STW 5 provides mechanistic insight contributing to its clinically-proven health benefits. Further research, will be valuable to confirm the translational relevance of these findings.

References

[1] Moissl-Eichinger, C. et al: Gastroenterol. 2017; 55: e57-e299. doi:10.1055/s-0037-1604872
[2] Thumann, T.A., et al: Microbiol Spectr. 2024;12(6):e0403123. doi:10.1128/spectrum.04031-23, and unpublished results
[3] Mohamed, S.S. et al: BMC Complement Med Ther. 2021;21(1):168. doi:10.1186/s12906-021-03337-8
[4] Khayyal, M.T. et al: Gastroenterology. 2017;152:S1009. doi:10.1016/S0016-5085(17)33423-6
[5] Khayyal, M.T. et al: Poster, ICNPR, Kraków, Poland. 2024.
[6] Allescher, H.D. et al: Gastrointest Liver Dis. 2020;29(2):227-233. doi:10.15403/jgld-814

Disclosure

JW and OK are empoloyees, LK was intern at Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany. MT has been obtaining speakers fees and travel support by Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany

Introduction

The modulation of gut microbiota through bioactive nutraceuticals offers promising avenues for managing gastrointestinal diseases such as ulcerative colitis (UC). In this study, we investigated the effects of two nutraceutical formulations, Biointestil® and Clovedin®, both rich in natural bioactive compounds, on the gut microbiota of healthy individuals and UC patients.

Aims & Methods

A standardized in vitro simulation of human gastrointestinal digestion and colonic fermentation was conducted using the MICODE (Multi-Unit Colon Model) platform, which through the replication of intestinal conditions including pH and O₂ milieu and specific gut microbiota enables conduct precise Risk/Benefit Assessment by omics means.
Biointestil® or Clovedin®. were subjected to 48-hour colonic fermentation with two different gut microbiota models: that from healthy and that from UC donors in biological duplicates.
Microbial composition was monitored using quantitative PCR (qPCR) targeting key pro-inflammatory and beneficial bacterial taxa. Changes in microbiota structure were evaluated through ecological indicators (i.e. prebiotic index, Firmicutes/Bacteroidota, etc), providing insight into gut microbial stability and resilience.
In addition, a comprehensive volatilome analysis was performed using SPME GC-MS to assess the metabolic output of the microbial communities, focusing on short-chain fatty acids (SCFAs), indoles, phenols, and other microbial metabolites.

Results

In addition, a comprehensive volatilome analysis was performed using SPME GC-MS to assess the metabolic output of the microbial communities, focusing on short-chain fatty acids (SCFAs), indoles, phenols, and other microbial metabolites. Treatment with Biointestil® and Clovedin® resulted in a reduction of some opportunistic and pro-inflammatory bacteria (Clostridiaceae, Collinsella aerofaciens, Desulfovibrio spp.) and a concurrent increase in some beneficial taxa (Bifidobacteriaceae, Ruminococcaceae, Faecalibacerium prausnitzii). These shifts were accompanied by an enhanced SCFA profile and a decreased production of toxic volatiles (p-cresol and skatole), particularly in the UC-derived microbiota.

Conclusion

The combined use of qPCR, volatilomics, and ecological modeling within the MICODE in vitro system provides a robust framework for assessing microbiota-targeted interventions and supports the therapeutic potential of Biointestil® and Clovedin® in inflammatory bowel disorders by remission of gut microbiota dysbiosis.

Introduction

Functional and organic bowel diseases in children often present with gastrointestinal (GI) symptoms, yet systematic data on symptom profiles at first presentation limited. Functional bowel disorders (FBD) are common and often require costly and invasive diagnostic procedures. The Pediatric Structured Assessment of Gastrointestinal Symptoms (pSAGIS) is a validated tool that facilitates structured and standardized symptom assessment in pediatric outpatient settings (1).

Aims & Methods

We aimed to compare GI symptoms at first presentation in children with subsequently diagnosed functional (FD), any organic bowel disease (aOD), and specifically inflammatory bowel disease (IBD) using the pSAGIS. The diagnosis of FD was based on the Rome IV criteria (2). From 2016 and 2023, 1550 children completed the pSAGIS questionnaire at their first outpatient visit at St. Anna Children’s Hospital, Vienna. The tool assesses 21 GI symptoms (five grades, from no problem (0) to very severe (4)), grouped into five domains: abdominal pain, dyspepsia, diarrhea, constipation, and dysphagia/nausea. Symptom severity scores (0–12 to 20, depending on the number of items in each domain) were analyzed using median ± SD; p < 0.05 was considered significant.

Results

Of all patients (n=1550), 17.7% (n=274) were excluded due to non-gastroenterological diagnoses. 28.7% (n=445) were diagnosed with FD and 53.6% (n=831) with aOD, including 7.2% (n=111) with IBD. The number of symptoms rated as present (mild to very severe) was 6.4±3.0 SD (FD) vs. 4.8±2.9 SD (aOD) vs. 4.3±2.5 SD (IBD) (FD vs. aOD and vs. IBD: p<0.001). The number of symptoms rated as moderate to very severe was 4.3±3.7 SD (FD) vs. 2.2±3.2 SD (aOD) vs. 2.0±3.1 SD (IBD) FD vs. aOD and vs. IBD: p<0.001).

Symptom scores in all five domains were significantly higher in the functional group:

Conclusion

Children with functional bowel disorders report significantly higher symptom burden at first presentation compared to those with organic disease, including IBD. In addition to its role in long-term monitoring of treatment outcomes, pSAGIS may support early symptom-based differentiation. This could support more targeted diagnostic pathways and inform timely therapeutic decisions in pediatric gastroenterology.

References

(1) Hammer J et al, JPGN 2023; (2) Hyams JS et al, Gastroenterology 2016.

Introduction

Sleep disturbances are more common in individuals with Irritable Bowel Syndrome (IBS) compared to healthy subjects. Sleep quality is an independent factor affecting gastrointestinal (GI) symptoms but the directionality of effects is unknown.

Aims & Methods

Our aim was to investigate relationships between subjective sleep quality, objective sleep measures and GI symptoms using actigraphy and the Experience Sampling Method (ESM). Single-centre, prospective, cross-sectional study conducted at the Wingate Institute of Neurogastroenterology in London, from March 2020 to May 2021. IBS patients were recruited from a tertiary neurogastroenterology clinic and the community. GI symptoms and mood were recorded on a smartphone application, ten times per day, over seven consecutive days (i.e. ESM). Subjective sleep quality was recorded every morning to reflect the night before. Objective measures of sleep quality were estimated from wrist-worn actigraphy. Cross-lagged structural equation models were built to assess the directionality of sleep-symptom relationships over time.

Results

Eighty IBS patients completed the study (mean age: 37 (range 20 – 68), 89% female, 78% community). The median IBS - Symptom Severity Score (IBS-SSS) score indicated moderate IBS severity (279 (IQR: 237-350)). Sixty-six % had a Pittsburgh Sleep Quality Index (PSQI) score ≥ 8 indicating a clinically significant sleep disturbance. Eighty-two % (95% CI: 72-90) screened positive for a sleep disorder, most commonly insomnia. Sleep efficiency, measured by actigraphy, was at the lower end of normal range (median: 86% (CI 95%: 85-87). In cross-lagged analysis, poor subjective sleep quality predicted next day abdominal pain (0.036 < p < 0.040) and lower GI symptoms (0.030 < p < 0.032), but not vice versa. Although the direction of the effect was the same for abdominal pain and lower GI symptoms, it was not significant for upper GI symptoms. No significant relationship with GI symptoms was found for any objective sleep measure.

Conclusion

Poor subjective sleep quality is associated with higher next day abdominal pain and lower GI symptom scores in IBS patients, but not vice versa. Objective sleep measures did not predict next day abdominal symptoms, potentially supporting the conclusion that it is the perception of sleep quality which is most influential. This study supports the use of real-time patient reported outcome measures when interpreting potential influencers of IBS symptoms and may be used to guide future research into the effect of sleep interventions on GI symptoms.

Disclosure

DK has received research funding from Grunenthal, Allergan, Will Pharma, Rome Foundation, ZonMw, MLDS, UEG, Horizon 2020, Horizon Europe, and speaker’s fee from Dr Falk (paid to host institution).
QA undergoes consulting work for Takeda Pharmacueticals, and Classado Biosciences Ltd.

Introduction

Bile acids malabsorption (BAM) is considered as a one of the possible mechanisms of the irritable bowel syndrome with diarrhea (IBS-D) development. Limitations of BAM first-line treatment – bile acid sequestrants – require investigation of new therapeutic approaches. Probiotic bacteria capable to produce bile salt hydrolase (BSH) are promising in the treatment of IBS-D and assumed BAM

Aims & Methods

The aim of the trial was to compare the effectiveness of combined treatment (a probiotic based on strains of Lactobacillus, Streptococcus, Bifidobacterium, Saccharomyces boulardii and cholestyramine) with cholestyramine monotherapy in the treatment of IBS-D.
Materials and methods: a 12-week randomized trial included 108 patients with IBS-D that were divided into 2 groups: a control group (n=51) receiving only cholestyramine (monotherapy) and an experimental group (n=57) receiving a combination of cholestyramine and the study probiotic (based on strains of Lactobacillus, Streptococcus, Bifidobacterium, Saccharomyces boulardii). Before the start of the treatment, the relative activity (RA) of the BSH of the investigated probiotic was determined using the ultraperformance liquid chromatography with mass spectrometry (UPLC-MS). During the stages of the study, patients were evaluated using clinical scales, including symptoms questionnaires with visual analog scale (VAS).

Results

The BSH RA of the studied probiotic was 2.07±0.06 U/ml compared to 1.0±0.04 U/ml of capsules with L. plantarum and 0.03±0.01 U/ml – with L. plantarum without BSH-genes. In the experimental group, the severity of bloating and visceral sensitivity index values were lower after 8 and 12 weeks, and the value of the type of stool according to the Bristol scale and its daily frequency – after 12 weeks compared to the control group, p<0.05 in all. According to the scale of IBS-adequate relief, the percentage of achieving a clinical effect was higher in the experimental group compared to the control group after 12 weeks, OR = 1.31 (95% CI; 1.03-1.68), p=0.038.

Conclusion

Additional prescribing of a probiotic with BSH producing bacterial strains was more effective in relieving the clinical manifestations of IBS-D and achieving a therapeutic effect compared to cholestyramine monotherapy.

Introduction

Irritable bowel syndrome (IBS) is a prevalent disorder of gut-brain interaction characterized by abdominal pain and altered bowel movements. While the pathophysiology underlying IBS is incompletely understood, local allergic reactions to foods are a candidate mechanism. Confocal laser endomicroscopy (CLE) has shown acute alterations of the duodenal epithelium in IBS within minutes of local food administration and these findings have been used to identify foods contributing to IBS symptoms. However, the mechanisms and relevance of the observed alterations remain elusive.

Aims & Methods

Aim: To visualize the effect of local food administration on the duodenal mucosa using CLE and assess whether visible changes are associated with altered permeability or markers of mast cell activation ex vivo.
Methods: Non-constipated Rome IV IBS patients with negative serum specific IgE for tested foods underwent baseline gastroscopy (EGD) and CLE performed during a second EGD. Duodenal mucosa was visualized using CLE at baseline and after luminal administration of foods (egg white, soy, milk, wheat, lyophilized fish and shellfish, and nuts solutions sequentially applied in a random order) through the working channel. Altered mucosa was defined as leakage of fluorescein into the lumen and presence of particles (previously termed “cell shedding”). Serum samples were taken at index endoscopy and 30 minutes after acute mucosal alterations. Biopsies were taken at index EGD and after visualized alterations to measure transepithelial electrical resistance (TEER) in Ussing chambers and tryptase levels in biopsy supernatants. Data are reported as mean ± SEM or median and IQR as appropriate.

Results

45 CLE exams were carried out in 28 patients (age 35±2 y, 93%f, BMI 24±1 kg/m2, mean IBS symptom severity score 320±20).
At baseline, mucosal alterations were present in 9% of exams (n=4), whereas all other exams (n=41) demonstrated alterations after food administration. The highest rate of acute alterations was observed after fish/shellfish mix (50%; 10 altered / 20 exposed). The rate of observed alterations per food is presented in the table. TEER was not altered after observed alterations vs baseline (25±0.8 Ωxcm² vs 25±1 Ωxcm²). Serum tryptase was not altered after food exposure vs baseline (ratio after/before = 0.9, IQR= 0.8-1.1, n=13). Tryptase release from biopsies increased after exposure compared to baseline in 5/9 (56%) of patients after one hour and in 13/19 (68%) patients after 24h. Overall, the average tryptase release of the tissue was 1.48-fold increased after food exposure compared to baseline in the first hour after exposure (IQR = 0.3-2.1, n=9) and 1.29-fold following 24h incubation (IQR = 0.9-2.1, n = 19).

Conclusion

In this group of IBS patients, we found a high rate of acute food-induced mucosal alterations as visualized with CLE. Ex vivo permeability was unaltered after observed alterations vs. baseline. Systemic tryptase remained unchanged after acute alterations compared to baseline whereas tryptase release from biopsies was increased following food exposure compared to baseline in more than half of patients.