Introduction

Motility function of the entire gastrointestinal tract belongs to the most complex and most fragile systems in human body. There is no single gold standard for its investigation. Usually, it is necessary to combine several methods. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects.

Aims & Methods

The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions (Ref. 1) to our own porcine experimental setting. Studies on gastrointestinal motility are of utmost importance, especially in the context of side effects induced by drugs, e.g. medication used for treatment of dementia and malignancies.
Five experimental adult female pigs (4-month-old; mean weight 41.2±5.5 kg; median 39.5 kg) were enrolled into the study. Medetomidine 0.1 mg/kg i.m., butorphanol 0.3 mg/kg i.m. and midazolam 0.3 mg/kg i.m. were used as an induction of anaesthesia. Subsequent short-term general anaesthesia was maintained by i.v. propofol (repeated one-mL boluses per 20 mg, in total less than 5 mL; time < 10 min.). Wireless motility capsules (SmartPill, Medtronic, Dublin, Republic of Ireland) were delivered into the middle part of the gastric body endoscopically. After full recovery from a short-term general anaesthesia, animals were free to move in unlimited manner with an unrestricted access to water. Food intake was allowed from four hours onwards. Data from wireless motility capsules were recorded for five days continuously, and these were available for subsequent detailed analysis.

Results

Records of animals provided good (3 pigs) or very good quality files (2 pigs). Mean time of overall recording was 6,537±712 min. (median 6,538 min.). In total, 31,150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926±295 min. (median 1,091 min.), transfer of a capsule from the stomach into the duodenum lasted 5 - 34 min. (median 8 min.). Capsules migrated back from the duodenum into the stomach spontaneously three times (for 13, 14 and 63 min.). Mean small intestinal transit time was 251±43 min. (median 233 min.). Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability.

Conclusion

This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. This will enable future experimental studies on gastrointestinal side effects of oncology chemotherapy. It will also facilitate further research of acetylcholinesterase inhibitors, modulators and reactivators and last but not least will extend possibilities of preclinical pharmacokinetic projects.
Acknowledgements: This work was supported by research projects DZVRO MO1012 and MH CZ - DRO (UHHK, 00179906).

References

Ref. 1: Henze et al. Characterization of gastrointestinal transit and luminal conditions in pigs using a telemetric motility capsule. Eur J Pharm Sci 2021; 156: 105627.

Introduction

The Atmo Capsule is a wireless motility capsule that senses and telemetrically transmits measurements of hydrogen (H₂) and carbon dioxide (CO₂) along the gut. In the colon, luminal concentrations of H₂ and CO₂ represent the metabolic activity of the microbial community. We hypothesized that delayed colonic transit would lead to altered gas profiles due to earlier depletion of fermentable substrates relative to transit time and/or facilitation of contact between methanogens and hydrogen (Levitt et al. CGH 2006).

Aims & Methods

The Atmo Capsule was administered to subjects with suspected upper and/or lower gut dysmotility. Colonic transit times (CTT) ≥ 59 h were considered delayed. Luminal H₂ and CO₂ concentrations (as time-normalized, area-under-the-curve [TN-AUC], [%.h]/h) were evaluated across the entire colon. Regional colonic profiles were evaluated per quartile of relative colonic transit, with quartiles 1 and 4 indicative of the proximal and distal colon, respectively. Gas measures were included if ≥ 50% of data were available for the corresponding segment. Fermentation profiles were estimated by the ratio of quartile 1:4 values, and time to peak concentrations were evaluated relative to CTT. Data were analyzed via Mann-Whitney test.

Results

The Atmo Capsule was administered to 209 subjects (median age 41; 188 female) with 170 yielding valid data on both colonic transit and colonic gas concentrations. Delayed colonic transit was identified in 60/170 (35%) subjects. In subjects with delayed CTT, H₂ concentrations tended to be higher in the proximal colon and lower in the distal colon with no overall difference across the region compared with those with normal transit (Table 1). CO₂ concentrations were higher throughout the colon except in the distal colon in subjects with delayed CTT. Peak concentrations of colonic H₂ and CO₂ were higher (H2, 8.7 h vs 5.9 %.h/h, p<0.01; CO2, 37.4 vs 29.9 %.h/h, p<0.01) and tended to occur earlier (H₂, 35.9 vs 47.0 % of colonic transit p=0.14; CO₂, 49.1 vs 86.8 % colonic transit, p<0.01) in patients with delayed compared with normal CTT.

Table 1. Gas profiles in patients with delayed colonic transit and correlation with symptom profiles. Data shown as median (interquartile range) and analyzed via Mann-Whitney test.

Conclusion

Colonic gas profiles, as measured via the Atmo Capsule, differed in patients with delayed compared with normal CTT, with patterns suggesting progressive depletion of fermentable substrates and/or conversion of H2 to methane during transit in those with delayed transit.

References

Levitt MD, Furne JK, Kuskowski M, Ruddy J. Stability of human methanogenic flora over 35 years and a review of insights obtained from breath methane measurements. Clin Gastroenterol Hepatol. 2006 Feb;4(2):123-9. doi: 10.1016/j.cgh.2005.11.006. PMID: 16469670.

Disclosure

These authors disclose the following: Braden Kuo, Anthony J. Lembo, Eammon M.M. Quigley, Satish S.C. Rao, and William D. Chey serve on the Medical Advisory Board of Atmo Biosciences. Michael Cline and Baharak Moshiree served on the Medical Advisory Board of Atmo Biosciences. Braden Kuo has received funding from NIH, Vanda, Atmo Biosciences, and Takeda and has consulted for Evoke, Takeda, Ironwood, Novo Nordisk, Cindome, and Neurogastrx. Thomas Abell has received funding from Gastric Dysrhythmias, Neurogastrx, NIH GpCRC, and Vanda and has consulted for Enterra Medical, Novo Nordisk, Nuvaira, and Vanda. Anthony J. Lembo has received funding from Ardelyx, Biomerica, GSK, Ironwood, Takeda, and Vibrant and holds stock with Allurion, Bristol Myer Squibb, and J&J. Abigail Stocker has received funding from Cindome, Enterra Medical, and Vanda. William D. Chey has received funding from Atmo Biosciences, Commonwealth Diagnostics Intl, QOL Medical, and Salix; has consulted for AbbVie, Ardelyx, Biomerica, Comvita, Gemelli, Ironwood, Nestle, QOL Medical, Phathom, Redhill, Salix, Vibrant, and Takeda; has filed patents with My Nutrition Health, Digital Manometry, and Rectal Expulsion Device; and holds stock options with Coprata, Evinature, Food Marble, Kiwi Bioscience, and Modify Health. The remaining authors disclose no conflicts.

Introduction

The functional lumen imaging probe (FLIP) relies on the principle of impedance planimetry that enables direct measurement of intraluminal cross-sectional areas, allowing the assessment of intraluminal diameters, lumen geometric profiles, and wall biomechanical properties. Electrical impedance refers to the opposition to alternating current presented by the combined effect of resistance and reactance in a closed circuit. Planimetrics is the study of plane measurements, including distances and areas. Since the early 2000s, impedance planimetry has been introduced into clinical practice, allowing principally assessment of any sphincter function / dysfunction. In humans, the functional lumen imaging probe is applied mostly to diseases of the oesophagus (achalasia, dysphagia, gastro-oesophageal junction outflow obstruction, eosinophilic oesophagitis, gastro-oesophageal reflux disease), pyloric distensibility (gastroparesis), and ano-rectal disorders (faecal incontinence). The physiology of the gastrointestinal tract of pigs is similar to that of humans, and therefore porcine experimental models are suitable for various endoscopic and preclinical studies.

Aims & Methods

Aims: The aim of our pilot project was to introduce this method to assess function of the lower oesophageal sphincter and pyloric muscle in experimental pigs.
Methods: All measurements were accomplished in one session under general anaesthesia in six adult female pigs (mean weight 34.2 ± 3.6 kg). EndoFLIP 1.0 System with EndoFLIP catheters (length of measuring zone 80 mm; 16 paired impedance planimetry sensors; filling volumes: 20, 30 and 40 mL). Five major parameters were evaluated for each filling volume: balloon pressure (mm Hg), estimated diameter (mm), cross-sectional area (mm²), distensibility defined as cross-sectional area divided by balloon distending pressure (mm²/mm Hg), and zone compliance defined as the change in volume over a 2-cm long segment spanning five electrodes, centred around the gastro-oesophageal junction or pylorus (mm³/mm Hg).

Results

In total, 180 particular readings were successfully accomplished, see Table 1. Most of the measured values were nearing lower average figures for the lower oesophageal sphincter and upper average figures for the pylorus in healthy humans. The porcine pyloric sphincter is composed of the torus pyloricus. It serves as a sturdy "gatekeeper" between the stomach and D1 duodenum, thus explaining higher pyloric readings. There was a clear trend for increasing values of CSA, diameter, and balloon pressure with increased filling balloon volumes. However, the sphincter distensibility did not change with increasing filling volumes either for the lower oesophageal sphincter or pylorus.

Table 1
Endoscopic functional luminal imaging probe panometry of the lower oesophageal sphincter and pylorus in six experimental pigs

Conclusion

Endoscopic functional luminal planimetry in experimental pigs is feasible, both for the lower oesophageal sphincter and the pylorus. This is an important starting point for future experimental endoscopic trials and pharmacology studies.

Introduction

Gut transit time is a key modulator of host-microbiome interactions, influencing gut microbiota composition and fecal metabolites concentrations. Prolonged colonic transit time is associated with greater microbial diversity, increased proteolytic fermentation activity and reduced concentrations of short-chain fatty acids (SCFAs). Metabolites derived from protein fermentation (such as ammonia, indole, p-cresol, and hydrogen sulfide) can impair epithelial integrity, while SCFAs, produced from nondigestible carbohydrates, support mucosal health through anti-inflammatory and antineoplastic effects. An imbalance between these metabolites may compromise colonic homeostasis, predisposing colonocytes to aberrant proliferation and increasing the risk of neoplastic transformation. These early alterations can be clinically detected through the presence of adenomatous polyps during colonoscopy, marking a critical window for preventive strategies.

Aims & Methods

The aim was to evaluate the role of gut transit time in shaping gut microbiota composition and fecal levels of bacterial-derived metabolites in individuals with a history of colorectal polyps. Thirty-three individuals who had undergone a colonoscopy were recruited and categorized based on gut transit time, assessed using the blue dye method. Fecal samples were collected and cocentrations of SCFAs, ammonium and indole were quantified using gas chromatography, a fluorometric assay and a colorimetric assay, respectively. The V3–V4 region of the 16S rRNA gene was sequenced using the Illumina NovaSeq platform. Sequence variant inference, quality filtering, chimera removal, and paired-end read merging were performed using the DADA2 pipeline in R, followed by taxonomic assignment with the Silva reference database. Alpha diversity was assessed by measuring richness (number of operational taxonomic units) and diversity (Shannon index). Beta diversity was analyzed using Canonical Correspondence Analysis (CCA) based on Bray–Curtis distances, with group differences tested via PERMANOVA. Linear discriminant analysis with an LDA score threshold >2 was applied to identify differentially abundant taxa.

Results

Alpha-diversity did not differ between groups with different gut transit times. Regarding Beta diversity, CCA based on Bray–Curtis distance showed a non-significant trend (p=0.095), whereas PERMANOVA analysis revealed a statistically significant effect (p=0.038), indicating that gut transit time explains a significant portion of the variance in microbial composition. Individuals with slow transit time exhibited an enrichment of several bacterial families from the phyla Actinobacteria (Micrococcaceae, Actinomycetaceae, Eggerthellaceae) and Firmicutes (Christensenellaceae, Ruminococcaceae, Lachnospiraceae, Peptostreptococcaceae and Veillonellaceae). A trend toward lower fecal SCFAs concentrations was observed in slow transit group compared to individuals with normal transit (69.2 ± 43.2 vs. 98.6 ± 34 umol/gr, p=0.087). No significant differences in fecal ammonium or indole concentrations were detected between groups. Multinomial logistic regression analysis indicated that higher levels of SCFA were linked to a lower likelihood of being in the slow transit group (p = 0.055). No differences were found in the frequency of polyp diagnosis according to transit time classification (p=0.495).

Conclusion

This study confirms that gut transit time influences both microbiota composition and SCFA levels. These findings highlight the relevance of gut transit modulation as a preventive target in individuals at risk of colorectal neoplasia.

Introduction

Accurate determination of withdrawal time (WT) is a critical quality metric within colonoscopy. While application of artificial intelligence (AI) to standardize WT estimation has been investigated, a critical need for further prospective validation exists.

Aims & Methods

We planned a prospective examiner-blinded evaluation to compare a novel AI system’s performance to that of physician assessment in routine colonoscopy from December 2023 to March 2024. Manual frame-by-frame video annotation provided the gold standard. The AI system autonomously generated detailed image reports, which were independently assessed by four endoscopists. (ClinicalTrials.gov NCT06094270).

Results

In the 126 analyzed examinations, our AI demonstrated a lower mean absolute error for WT estimation achieved by the AI system with 2.17 minutes compared to physician assessments with 4.23 minutes, p<0.01. Achieving mean 97% satisfaction with the timeline representation and 81% overall satisfaction, the AI generated comprehensive image reports.

Conclusion

These findings establish the potential of the AI system to improve efficiency and precision in WT calculation in clinical practice. This work represents a critical step towards integrating AI-driven solutions for optimizing clinical workflows and enhancing the quality of colorectal cancer screening.

Introduction

With the improvement of endoscopic resection techniques, there has been recent interest in real-time in vivo characterization of polyp histology. Of all the new imaging technologies for characterizing polyp histology, narrow-band imaging (NBI) has been the most extensively studied and is easy to feasible. Correct histological prediction allows determining the optimal endoscopic technique for resection of lesions with the achievement of R0 resection. The NBI International Colorectal Endoscopic Classification (NICE) and the Japanese NBI Expert Team (JNET) classification are mostly used to predict the depth of invasion. However, the effectiveness of diagnostics using NBI in clinical practice is variable and is associated with low sensitivity for superficial invasive carcinoma.

Aims & Methods

Primary aim was to determine and compare the diagnostic accuracy of NICE and JNET classifications in predicting histology in community practice. Secondary aim was to determine the positive predictive value (PPV) for the NICE and JNET classification.
In this single-center prospective study we have included 211 patients aged 18–75 years (130 men, 62%; 81 women, 38%; mean age 60 years) who underwent colonoscopies with endoscopic resection of advanced colorectal neoplasia (defined by size lesions ≥ 10 mm). The NICE and JNET classifications were used for each lesion. The results were compared with the final histopathological finding to determine and compare NICE and JNET classification accuracy.

Results

257 lesions were analyzed including 8 (3.1 %) hyperplastic polyps, 47 (18.3 %) sessile serrated polyps, 152 (59.1 %) adenomas with low grade dysplasia, 36 (14.0 %) high-grade adenomas, 12 (4,7 %) intramucosal carcinomas, 1 (0.4 %) T1sm1 carcinoma and 1 (0.4 %) T2 carcinoma. A total of 199 lesions (77.4 %) were correctly classified according to the JNET classification and 241 lesions (93.8 %) were correctly classified according to the NICE classification. The PPV for NICE 1 lesion was 95.9 %, NICE 2 97.0 % and NICE 3 22.0 %. The PPV for JNET 1 lesions was 95.9 %, JNET 2A 83.0 %, JNET 2B 52.2 % and JNET 3 22.5 %.

Conclusion

The NICE classification was associated with a higher proportion of correctly classified lesions (93.8 %) compared to the JNET classification (77.4 %). However, NBI virtual chromoendoscopy shows a low PPV for HGD adenomas, intramucosal carcinomas and T1sm1 carcinomas (NICE 2 22.1 %, JNET 2B 52.2 %). Therefore, additional investigations in these lesions are still required with magnifying chromoendoscopy prior a final decision of endoscopic therapy. Improvement of predictive accuracy of these lesions and determining the limiting factors will be the subject of further investigation.
Supported by program projects of the Ministry of Health of the Czech Republic with reg. no. NV18-08-00246, NU22-08-00424, MO1012 and Cooperatio.

References

Kobayashi S et al. Diagnostic yield of the Japan NBI Expert Team (JNET) classification for endoscopic diagnosis of superficial colorectal neoplasms in a large-scale clinical practice database. United European Gastroenterology Journal 2019;7(7):914- 923.
Hayashi N et al. Endoscopic prediction of deep submucosal invasive carcinoma: validation of the narrow-band imaging international colorectal endoscopic (NICE) classification. Gastrointest Endosc 2013;78:625–632.
Sano Y et al. Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team. Dig Endosc 2016;28:526–533.
Wang Y et al. Diagnostic performance of narrow-band imaging international colorectal endoscopic and Japanese narrow-band imaging expert team classification systems for colorectal cancer and precancerous lesions. World J Gastrointest Oncol 2021;13(1):58-68.

Introduction

Gastrointestinal (GI) symptoms and their relationship with measures of GI function are incompletely understood.

Aims & Methods

We included patients investigated with OATT by use of radiopaque markers (ROM) between 2000 and 2022; one clinical audit cohort investigated because of disturbed bowel habits, and a cohort from IBS trials. In the clinical audit cohort, information on bowel habits were retrieved from referral notes and severity of abdominal pain, bloating and flatulence were rated daily by the patients during the week of the OATT measurement. In IBS patients, information on IBS subtype (IBS-C, IBS-D, IBS nonCnonD), severity of GI symptoms (GSRS), and stool frequency and consistency (Bristol stool form) from stool diaries were available. The aim of this study was to assess the outcome of oro-anal transit time (OATT) investigations in patients with disturbed bowel habits and its association with GI symptoms.

Results

We included 1142 patients (75% females) with a median age of 37(range 20-65) years with bowel symptoms. In the clinical audit cohort, slow transit was most common among patients with constipation (41%), whereas rapid transit was most frequent in patients with diarrhea (32%). In line with this, slow transit was predominantly seen in IBS-C (17%) and rapid transit in IBS-D (30%). However, in both cohorts, normal transit was most frequent.
Among patients in the clinical audit cohort, a positive correlation between OATT and the severity of bloating (r=0.17, p<0.001) was seen, but there was no association with abdominal pain (r=0.02, p=0.72) or flatulence (r=-0.10, p=0.07). In IBS patients, inverse correlations were seen between OATT and stool consistency (r=-0.38, p<0.0001), and frequency (r=-0.32, p<0.0001). In line with this, OATT was associated with the severity of diarrhea (r=-0.16, p<0.05), and constipation (r=0.27, p<0.001). In addition, a weak, but significant association was seen with satiety (r=0.16, p<0.05) but not with abdominal pain (r=0.06; p=0.23) or bloating (0.08; p=0.09).

Conclusion

Abnormal OATT is prevalent among patients with disturbed bowel habits and is a pathophysiologic mechanism of importance for the understanding of stool frequency and consistency, and the severity of diarrhea and constipation but less so with other GI symptoms.