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THE GUT MICROBIOME IN END-STAGE LUNG DISEASE AND LUNG TRANSPLANTATION

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Introduction

Lung transplantation (LT) is a life-saving therapy for patients with end-stage lung diseases (ESLD patients), but the long-term outcomes of lung transplant recipients (LTR) remain unsatisfactory due to high mortality and probability of developing chronic lung allograft dysfunction (CLAD) ^1,2. The gut microbiome has been found to influence lung immunity via a bidirectional crosstalk between the gut and lungs called the “gut-lung axis” ^3,4. ESLD patients often suffer from gut dysbiosis ^5,6, which has previously been reported in kidney and liver transplant recipients ⁷. However, studies exploring the roles of gut microbiome in LTR are still lacking.

Aims & Methods

In this study, we aimed to investigate the extent of gut dysbiosis before and after LT, gut microbial signatures of different end-stage lung diseases, and gut microbiome alterations in LTR on different medication regimens and in different CLAD stages.
We characterized the gut microbiome of 64 fecal samples from ESLD patients before LT and 219 samples from LTR after LT by metagenomic sequencing. 243 fecal samples from age-, sex-, and BMI-matched healthy controls (HC) were also analyzed to quantify the extent of gut dysbiosis before and after LT. We quantified differences in alpha (with the Shannon diversity index), beta diversity (with the Aitchison distance) and individual (centered log ratio-transformed) abundances of microbial species and metabolic pathways. By presence-absence analysis, we also assessed differences in antibiotic resistance genes (ARGs) and virulence factors (VFs). By differential abundance analysis, we identified gut microbial signatures in ESLD patients and tested if those signatures remained in LTR treated for the same end-stage lung disease after LT. By unsupervised clustering, we identified five groups of LTR on different combinations of immunosuppressants and antibiotics which were associated with different microbial signatures. We also quantified differences in gut microbiome composition between HC and LTR in different CLAD stages. Finally, we investigated short and long-term microbiome changes in LTR that were followed longitudinally after LT.

Results

Our data show that gut dysbiosis is present before LT and exacerbated after LT, including decreased microbial diversity, reduced abundance of beneficial species and important metabolic pathways, and higher prevalence of ARGs and VFs. For example, compared with HC, we found that Clostridlum symblosum, Vellonella dispar, and Streptococcus parasangunis exhibited significantly higher abundances in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis or pulmonary arterial hypertension, and in LTR treated for the same diseases. All else equal, we found that LTR using macrolide antibiotics exhibited significantly lower abundances of several gut commensals, including Faecalibacterium prausnitzi, Roseburia hominis and Bifidobacterium longum. Compared with HC, LTR in CLAD1 exhibited elevated dysbiosis compared to those in CLAD0. Finally, gut microbial diversity of LTR does not recover to healthy levels, not even after 20 years after LT.

Conclusion

Gut microbiome dysbiosis is present in ESLD patients and is further exacerbated in LTR after LT. Gut microbiome alterations are associated with different types of end-stage lung disease, medication regimens and CLAD stages. Our study gives insight into the gut microbiome of LTR which could potentially contribute to microbiome-targeted interventions for improving the outcomes after LT.

References

1. Bos, S., Vos, R., Van Raemdonck, D. E. & Verleden, G. M. Survival in adult lung transplantation: where are we in 2020? Curr. Opin. Organ Transplant. 25, 268–273 (2020).
2. Yeung, J. C. & Keshavjee, S. Overview of Clinical Lung Transplantation. Cold Spring Harb. Perspect. Med. 4, a015628 (2014).
3. Wang, Y.-H. et al. Gut microbiota-derived succinate aggravates acute lung injury after intestinal ischaemia/reperfusion in mice. Eur. Respir. J. 61, (2023).
4. Zhang, D. et al. The Cross-Talk Between Gut Microbiota and Lungs in Common Lung Diseases. Front. Microbiol. 11, 301 (2020).
5. Bowerman, K. L. et al. Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease. Nat. Commun. 11, 5886 (2020).
6. Wu, Y. et al. Gut microbiome and metabolites: The potential key roles in pulmonary fibrosis. Front. Microbiol. 13, (2022).
7. Swarte, J. C. et al. Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation. Sci. Transl. Med. 14, eabn7566 (2022).

THE GUT MICROBIOME IN END-STAGE LUNG DISEASE AND LUNG TRANSPLANTATION

Shuyan Zhang 1, J Casper Swarte 1, Ranko Gacesa 1, Tim J. Knobbe 2, Daan Kremer 2, Dianne Jansen 2, Martin H. de Borst 2, Hermie J. M. Harmsen 2, Erik A. M. Verschuuren 2, Stephan J. L. Bakker 2, C. Tji Gan 2, Johannes R. Björk 1, Rinse K. Weersma 2

1 University Medical Center Groningen, Groningen, Netherlands|||University Medical Center Groningen, Groningen, Netherlands

2 University Medical Center Groningen, Groningen, Netherlands

Event

UEG Week Copenhagen 2023

Topics

Gut Microbiota IBD Mechanisms & Personalised Medicine Colorectal

Submission format

Abstract

Session

The gut microbiome as a driver of disease

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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EVALUATION OF SUBCUTANEOUS INFLIXIMAB FOR PERIANAL FISTULA HEALING IN CROHN’S DISEASE: PRELIMINARY RESULTS FROM THE REMSILAP MULTICENTER OBSERVATIONAL COHORT STUDY

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Introduction

Management of perianal fistulas in Crohn’s disease (CD) is challenging and requires a multidisciplinary approach, combining surgical drainage and biologic therapies, such as infliximab (IFX). Higher IFX trough concentrations have been associated with improved fistula healing rates. The subcutaneous (SC) formulation of IFX achieves 2–3 times higher and more stable trough levels compared to intravenous (IV) formulation. This study hypothesizes that SC IFX could enhance perianal fistula healing rates in CD patients.

Aims & Methods

REMSILAP study is part of the 3TLAP cohort, a French prospective multicenter observational study evaluating optimal therapeutic strategies for achieving clinical and radiological remission of perianal fistulas in CD at 12 months post-surgical drainage. The REMSILAP substudy focuses specifically on patients receiving SC IFX. Patients who received SC IFX after or within six months prior to surgical drainage were included. Baseline was defined as the day of surgical drainage. The primary outcome was the proportion of patients achieving complete clinical remission defined as Perianal Disease Activity Index (PDAI) fistula drainage subscore = 0 associated with PDAI activity restriction subscore <3 and absence of seton, and radiological remission at 12 months. Here, we present preliminary findings from REMSILAP.

Results

Among the 353 patients enrolled in the 3TLAP cohort, 54 were included in REMSILAP. The cohort consisted of 61.1% male patients, with a median age of 36 years and a median disease duration of 4.5 years. Penetrating disease (B3 phenotype) was present in 40.7%, and 33.3% had a history of surgical resection. At baseline, 40.7% of patients had quiescent disease regarding Harvey-Bradshaw index, while 5.6% had severe disease activity. Biologic exposure prior to inclusion was noted in 42.6%. Surgical drainage, with seton placement, was performed in 74.1% of patients. Forty-eight patients (88%) initiated SC IFX treatment after surgical drainage. Of the patients receiving SC IFX, 50% transitioned to SC IFX after less than three IV infusions. Among those on IV IFX at baseline, 20.4% were receiving a 10 mg/kg dose. Forty-three patients (79.6%) received SC IFX in combination with immunomodulators (azathioprine, methotrexate, or 6-mercaptopurine). The median duration of SC IFX treatment was 13.1 months, with treatment maintained for 67.5% of the follow-up period (mean: 19.3 ± 11.3 months). Forty-three patients (79.6%) were treated with a stable dose of 120 mg/14 days and 6 patients (11.1%) had an intensification of SC IFX dosage to 120mg / 7 days. At 12 months, 42 patients were evaluable for clinical outcomes. Complete clinical healing at 12 months was achieved in 11 patients (27.5%) and association of PDAI restriction subscore <3 and drainage subscore = 0 was found in 18 patients (42.9%). Thirteen patients (34.2%) from the 25 patients who had received at least 6 months of SC IFX treatment showed clinical healing at 6 months. Out of the 26 patients treated with at least 12 months of SC IFX treatment, clinical healing was achieved in 16 patients (61.5%) at 12 months. Among the 11 patients with clinical healing at 12 months, 8 (72.2%) were treated with SC IFX treatment following more than three IFX IV infusions. None of the 11 patients with available MRI date showed radiological healing at 12 months.

Conclusion

Subcutaneous infliximab following surgical drainage of Crohn’s disease perianal fistula demonstrates high treatment persistence and promising rates of fistula healing.

Disclosure

This study was funded by Celltrion Healthcare France

EVALUATION OF SUBCUTANEOUS INFLIXIMAB FOR PERIANAL FISTULA HEALING IN CROHN’S DISEASE: PRELIMINARY RESULTS FROM THE REMSILAP MULTICENTER OBSERVATIONAL COHORT STUDY

Manon Haas 1, Laurent Abramowitz 2, Stephanie Hamonic 3, Amandine Landemaine 3, Guillaume Bouguen 3, Anne Laurain 2, Lucine Vuitton 4, Isabelle Etienney 5, Gauthier Pellet 6, Kristell Coat 3, Ronan Garlantezec 3, Laurent Siproudhis 3, Xavier Treton 1

1 Institut des MICI - Clinique Ambroise Paré Hartmann, Neuilly sur Seine, France

2 CHU Bichat, Paris, France

3 CHU Pontchaillou, Rennes, France

4 Besançon university hospital gastroenterology, Courbevoie, France

5 Diaconesses-Croix St Simon Hospital, Paris, France

6 CHU Bordeaux, Bordeaux, France

Event

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Treatment of fistulas in Crohn's disease

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

The STRIDE-II consensus on the management of Crohn’s disease (CD) highlights the importance of achieving multiple treatment targets, including clinical remission, normalisation of the inflammatory biomarkers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP), and quality of life (QoL) improvements.¹ In this post hoc analysis of the SEQUENCE open-label extension (OLE), we assessed inflammatory biomarker reductions and improvements in clinical and QoL outcomes (alone or in combination) in patients (pts) with moderately to severely active CD treated with risankizumab (RZB), an interleukin-23 p19 inhibitor.

Aims & Methods

In Part 2 of SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 and who completed the week (wk) 48 visit were eligible to continue receiving open-label 360mg subcutaneous RZB maintenance dose every 8 wks.² This analysis included all patients who completed wk100 of RZB treatment or who discontinued treatment prior to wk100 in Part 2 (cutoff date: July 11, 2024). Pts with elevated hs-CRP (> 5 mg/L) or FCP (> 250 mg/kg) at induction baseline were assessed for achievement of normalised hs-CRP or FCP alone or in combination with clinical remission per CD activity index (CDAI) or per stool frequency/abdominal pain score (SF/APS), or with inflammatory bowel disease questionnaire (IBDQ) remission (endpoints defined in Table footnote) at wks 52 (OLE baseline), 76, and 100. Data were assessed for all intent-to-treat pts using as observed (AO) regardless of rescue therapy and nonresponder imputation (NRI). Safety was previously reported and not assessed in this post hoc analysis.³

Results

Of the 224 pts who entered SEQUENCE Part 2, 184 pts had elevated hs-CRP or FCP levels at induction baseline and were included in this analysis. The majority of these pts achieved normalisation of hs-CRP or FCP (per AO data) at wk52 (77.7%) and continued to show improvement at wks 76 and 100 (83.9% and 86.6%, respectively) (Table). Most of these pts also achieved both normalised hs-CRP or FCP and clinical remission simultaneously at wks 52, 76, and 100 per CDAI (AO data: 60.9%, 66.2%, and 71.0%, respectively) and per SF/APS (AO data: 55.2%, 60.2%, and 62.9%, respectively). The proportion of pts who achieved normalisation of hs-CRP or FCP and IBDQ remission increased from wk52 through wk100 (AO data; wk52: 50.0%, wk76: 54.9%, wk100: 57.1%). NRI data for all endpoints are summarized in the Table.

Endpoint, n/N (%) [95% CI]^a	AO^b	NRI^c
Normalisation of hs-CRP^d or FCP^e Week 52 Week 76 Week 100 Normalisation of hs-CRP or FCP and CDAI clinical remission^f Week 52 Week 76 Week 100 Normalisation of hs-CRP or FCP and SF/APS clinical remission^g Week 52 Week 76 Week 100 Normalisation of hs-CRP or FCP and IBDQ remission^h Week 52 Week 76 Week 100	143/184 (77.7) [71.7, 83.7] 141/168 (83.9) [78.4, 89.5] 136/157 (86.6) [81.3, 91.9] 112/184 (60.9) [53.8, 67.9] 88/133 (66.2) [58.1, 74.2] 93/131 (71.0) [63.2, 78.8] 101/183 (55.2) [48.0, 62.4] 80/133 (60.2) [51.8, 68.5] 83/132 (62.9) [54.6, 71.1] 92/184 (50.0) [42.8, 57.2] 89/162 (54.9) [47.3, 62.6] 88/154 (57.1) [49.3, 65.0]	143/184 (77.7) [71.7, 83.7] 140/184 (76.1) [69.9, 82.3] 130/184 (70.7) [64.1, 77.2] 112/184 (60.9) [53.8, 67.9] 86/184 (46.7) [39.5, 53.9] 89/184 (48.4) [41.1, 55.6] 101/184 (54.9) [47.7, 62.1] 78/184 (42.4) [35.3, 49.5] 79/184 (42.9) [35.8, 50.1] 92/184 (50.0) [42.8, 57.2] 88/184 (47.8) [40.6, 55.0] 85/184 (46.2) [39.0, 53.4]
Table. Achievement of Endpoints in Patients With Elevated hs-CRP or Elevated FCP at Baseline. Abbreviations: AO, as observed; CDAI, Crohn’s Disease Activity Index; FCP, fecal calprotectin; hs-CRP; high-sensitivity C-reactive protein; IBDQ, Inflammatory Bowel Disease Questionnaire; NRI, nonresponder imputation; SF/APS, stool frequency/abdominal pain score. The study population includes all intent-to-treat patients who received at least one dose of study drug in the SEQUENCE OLE. ^aConstruction of CIs for response rate is based on the normal approximation to the binomial distribution. ^b16 patients received at least one dose of rescue therapy during Part 2. ^cOnly patients with 2-year matured data or those who discontinued the study before the cutoff date (n = 26) are included in the NRI analysis. Pts were categorised as nonresponders for visits with missing assessments, visits after premature discontinuation of study, and visits after initiation of rescue therapy (if applicable). ^dC-reactive protein (hs-CRP) ≤ 5 mg/L. ^eFCP ≤ 250 mg/kg. ^fCDAI clinical remission: CDAI < 150. ^gSF/APS clinical remission: Average daily SF ≤ 2.8 and not worse than baseline value and average daily APS ≤ 1 and not worse than baseline value. ^hIBDQ remission is defined as IBDQ total score ≥170 points.

Conclusion

In this post hoc analysis, pts with moderately to severely active CD demonstrated inflammatory biomarker normalisation with RZB treatment and continued improvement of inflammation up to wk100 in the SEQUENCE OLE. Notably, most pts simultaneously achieved normalisation of inflammatory biomarkers plus clinical or QoL outcomes through wk100 of RZB treatment.

References

Turner D, et al. Gastroenterology. 2021;160:1570–83.
Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.
L Peyrin-Biroulet, et al. Journal of Crohn's and Colitis. 2025;19(Supplement_1):i1405–07.

Disclosure

Benjamin L. Cohen has received advisory board and consultancy fees from AbbVie, ALPCO, Celgene-Bristol Myers Squibb, Johnson & Johnson Innovative Medicine, Lilly, Pfizer, Sublimity Therapeutics, Takeda, TARGET RWE; DSMB: Emmes Biopharma Services LLC; speakers’ fees from AbbVie and Takeda.
Corey Siegel has served as a consultant for AbbVie, BMS, Boomerang, Buhlmann, Celltrion, Johnson & Johnson, Lilly, Napo Pharmaceuticals, Path Healthcare, Pfizer, Prometheus Biosciences & Labs, Sanofi, Takeda, and Trellus Health; received grants from AbbVie, Johson & Johnson, Pfizer, and Takeda; and is co-founder of MiTest Health, LLC, technology “System and Method of Communicating Predicted Medical Outcomes” licensed to Takeda; equity interest in Path Healthcare and Trellus Health
Alessandro Armuzzi has received consulting/advisory board fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; speaker’s fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; and research support from MSD, Takeda, Pfizer, and Biogen.
Fernando Aponte, Toni Anschutz, Andrew Garrison, Namita Joshi, and Javier Zambrano are full-time employees of AbbVie and may own AbbVie stock or stock options.
Laurent Peyrin-Biroulet has received personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio.

Funding
AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. Medical writing support was provided by Mahesh Chemudupati, PhD of AbbVie. Editorial support was provided by Amy Kuang, PhD of AbbVie.

INFLAMMATORY BIOMARKER REDUCTIONS AND IMPROVEMENTS IN CLINICAL AND QUALITY OF LIFE OUTCOMES WITH RISANKIZUMAB THROUGH 100 WEEKS OF TREATMENT IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE: A POST HOC ANALYSIS FROM PART 2 OF THE SEQUENCE TR

Benjamin L. Cohen 1, Corey A Siegel 2, Alessandro Armuzzi 3, Fernando Aponte 4, Toni Anschutz 4, Andrew Garrison 4, Namita Joshi 4, Javier Zambrano 4, Laurent Peyrin-Biroulet 5

1 Cleveland Clinic Foundation, Cleveland, OH, United States

2 Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States

3 IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

4 AbbVie Inc, North Chicago, IL, United States

5 INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France|||McGill University Health Centre, Montreal, Canada

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

New treatments on the horizon for Crohn's disease (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Prediction of Clinical Events in Patients with MASLD Based on Baseline and Serial Changes in MRE

Takashi Kobayashi 1

1 Yokohama City University Graduate School of Medicine, Yokohama, Japan

Event

UEG Week Berlin 2025

Topics

Hepatobiliary

Session

Rising Stars from Europe and Japan: Metabolic liver diseases

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Despite the benefits of available therapies for Crohn’s disease (CD), many patients (pts) lose treatment response over time, highlighting the need for options with sustained effectiveness.^1-3 Part 2 of the SEQUENCE trial is an open-label extension (OLE) study that evaluates the long-term efficacy and safety of the interleukin-23 p19 inhibitor risankizumab (RZB) in pts with moderate to severe CD and prior anti-TNF failure. Here, we evaluated the durability of clinical remission, quality of life (QoL), and inflammatory biomarker outcomes in RZB-treated pts through week (wk) 100 of SEQUENCE.

Aims & Methods

In SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 who completed the wk48 visit continued to receive open-label 360mg subcutaneous RZB maintenance dose every 8 wks starting at wk52 (baseline of Part 2).⁴ We assessed the proportion of pts achieving clinical remission (per CD activity index [CDAI] and stool frequency/abdominal pain score [SF/APS]) and Inflammatory Bowel Disease Questionnaire (IBDQ) remission at wks 8, 24, 52, 76, and 100. Additionally, pts with elevated high-sensitivity C-reactive protein (hs-CRP; > 5 mg/L) or faecal calprotectin (FCP; > 250 µg/g) at baseline were assessed for normalization of hs-CRP or FCP at wks 8, 24, 52, 76, and 100. We also assessed the proportion of pts who achieved these endpoints at wk100 among pts who also achieved that endpoint previously at either wk8 or at wk52. Data were assessed for all intent-to-treat pts using As Observed (AO) and per Non Responder imputation (NRI). Safety was not assessed in this post hoc analysis, although previously reported.⁵

Results

Of the 224 pts who entered SEQUENCE Part 2, the proportion of pts who achieved clinical remission (per AO data) increased from wk8 to wk52, and remained stable up to wk100 (CDAI: 48.0% [n/N=96/200] at wk8, 75.3% [168/223] at wk52, and 84.4% [141/167] at wk100; SF/APS: 44.0% [88/200] at wk8, 71.2% [158/222] at wk52, and 74.7% [124/166] at wk100) (Table). Similar trends were observed (per AO data) for IBDQ remission (41.5% [88/212] at wk8, 62.1% [139/224] at wk52, and 65.3% [126/193] at wk100), normalisation of hs-CRP (38.8% [54/139] at wk8, 53.1% [76/143] at wk52, and 62.0% [80/129] at wk100), and normalisation of FCP (34.6% [46/133] at wk8, 56.9% [87/153] at wk52, and 60.0% [75/125] at wk100). Most pts who achieved clinical remission at wk8 remained in remission at wk100, and the same was observed for patients in remission at both wk52 and wk100 (AO data; respectively, CDAI: 96.1% [73/76] and 91.1% [123/135]; SF/APS: 90.1% [64/71] and 86.8% [112/129]). A durable effect was also observed from wk8 to wk100 and from wk52 to wk100 in the majority of RZB-treated pts across all other endpoints (AO data; respectively, IBDQ remission: 91.5% [65/71] and 85.7% [102/119]); normalisation of hs-CRP: 80.0% [40/50] and 81.2% [56/69]; normalisation of FCP: 81.1% [30/37] and 85.1% [57/67]). Similar results to AO data were observed per NRI data (Table).

Endpoint, n/N (%) [95% CI]^a	AO^b	NRI^c
CDAI clinical remission^d Week 8 Week 24 Week 52^e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 SF/APS clinical remission^f Week 8 Week 24 Week 52^e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 IBDQ remission^g Week 8 Week 24 Week 52^e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 Normalisation of hs-CRP^h Week 8 Week 24 Week 52^e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52 Normalisation of FCPⁱ Week 8 Week 24 Week 52^e Week 76 Week 100 Week 100 among pts who achieved at Week 8 Week 100 among pts who achieved at Week 52	96/200 (48.0) [41.1, 54.9] 148/199 (74.4) [68.3, 80.4] 168/223 (75.3) [69.7, 81.0] 140/168 (83.3) [77.7, 89.0] 141/167 (84.4) [78.9, 89.9] 73/76 (96.1) [91.7, 100.0] 123/135 (91.1) [86.3, 95.9] 88/200 (44.0) [37.1, 50.9] 135/198 (68.2) [61.7, 74.7] 158/222 (71.2) [65.2, 77.1] 125/167 (74.9) [68.3, 81.4] 124/166 (74.7) [68.1, 81.3] 64/71 (90.1) [83.2, 97.1] 112/129 (86.8) [81.0, 92.7] 88/212 (41.5) [34.9, 48.1] 129/212 (60.8) [54.3, 67.4] 139/224 (62.1) [55.7, 68.4] 135/201 (67.2) [60.7, 73.7] 126/193 (65.3) [58.6, 72.0] 65/71 (91.5) [85.1, 98.0] 102/119 (85.7) [79.4, 92.0] 54/139 (38.8) [30.7, 47.0] 68/139 (48.9) [40.6, 57.2] 76/143 (53.1) [45.0, 61.3] 82/139 (59.0) [50.8, 67.2] 80/129 (62.0) [53.6, 70.4] 40/50 (80.0) [68.9, 91.1] 56/69 (81.2) [71.9, 90.4] 46/133 (34.6) [26.5, 42.7] 64/129 (49.6) [41.0, 58.2] 87/153 (56.9) [49.0, 64.7] 71/130 (54.6) [46.1, 63.2] 75/125 (60.0) [51.4, 68.6] 30/37 (81.1) [68.5, 93.7] 57/67 (85.1) [76.5, 93.6]	94/224 (42.0) [35.5, 48.4] 145/224 (64.7) [58.5, 71.0] 168/224 (75.0) [69.3, 80.7] 136/224 (60.7) [54.3, 67.1] 134/224 (59.8) [53.4, 66.2] 70/94 (74.5) [65.7, 83.3] 117/168 (69.6) [62.7, 76.6] 88/224 (39.3) [32.9, 45.7] 133/224 (59.4) [52.9, 65.8] 158/224 (70.5) [64.6, 76.5] 121/224 (54.0) [47.5, 60.5] 117/224 (52.2) [45.7, 58.8] 61/88 (69.3) [59.7, 79.0] 107/158 (67.7) [60.4, 75.0] 86/224 (38.4) [32.0, 44.8] 126/224 (56.3) [49.8, 62.7] 139/224 (62.1) [55.7, 68.4] 133/224 (59.4) [52.9, 65.8] 122/224 (54.5) [47.9, 61.0] 62/86 (72.1) [62.6, 81.6] 99/139 (71.2) [63.7, 78.7] 54/143 (37.8) [29.8, 45.7] 67/143 (46.9) [38.7, 55.0] 76/143 (53.1) [45.0, 61.3] 80/143 (55.9) [47.8, 64.1] 77/143 (53.8) [45.7, 62.0] 40/54 (74.1) [62.4, 85.8] 53/76 (69.7) [59.4, 80.1] 46/153 (30.1) [22.8, 37.3] 64/153 (41.8) [34.0, 49.6] 87/153 (56.9) [49.0, 64.7] 71/153 (46.4) [38.5, 54.3] 73/153 (47.7) [39.8, 55.6] 29/46 (63.0) [49.1, 77.0] 56/87 (64.4) [54.3, 74.4]
Table. Achievement of Endpoints Over Time and at Week 100 in Patients Who Achieved Endpoints at Weeks 8 and 52. Abbreviations: AO, as observed, CDAI, Crohn’s Disease Activity Index; FCP, faecal calprotectin; hs-CRP; high-sensitivity C-reactive protein; IBDQ; Inflammatory Bowel Disease Questionnaire; NRI, nonresponder imputation; OLE, open-label extension; pt, patient; SF/APS, stool frequency/abdominal pain score. The study population includes all intent-to-treat patients who received at least one dose of study drug in the SEQUENCE OLE. ^aConstruction of CIs for response rate is based on the normal approximation to the binomial distribution. ^bFor the AO analysis, data were used as is; 16 patients received at least one dose of rescue therapy during Part 2. ^cOnly patients with 2-year matured data or those who discontinued the study early are included in the NRI analysis. Pts were categorised as non-responders for visits with missing assessments, visits after premature discontinuation of study, and visits after initiation of rescue therapy (if applicable). ^dCDAI clinical remission: CDAI < 150. ^eValues for wk52 represent the most recent non-missing assessment prior to the start of Part 2. ^fSF/APS clinical remission: Average daily SF ≤ 2.8 and not worse than baseline value and average daily APS ≤ 1 and not worse than baseline value. ^gIBDQ remission is defined as IBDQ total score ≥ 170 points. ^hC-reactive protein (hs-CRP) ≤ 5 mg/L. ⁱFCP ≤ 250 µg/g.

Conclusion

Pts with moderately to severely active CD receiving RZB demonstrated durable clinical remission, IBDQ remission, and inflammatory biomarker reductions through wk100 in the SEQUENCE OLE. Notably, most pts who achieved efficacy endpoints early maintained effectiveness during continued RZB treatment.

References

Colombel JF, et al. Gastroenterology. 2007;132:52–65.
Hanauer SB, et al. Lancet. 2002;359:1541–9.
Turner D, et al. Gastroenterology. 2021;160:1570–83.
Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.

Disclosure

Raja Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, AstraZeneca, Bristol Myers Squibb, CED Service, Celltrion Healthcare, Dr Falk, Galapagos, Johnson & Johnson, Eli Lilly, MSD Sharp & Dohme, Pfizer, Takeda Pharma.
James O. Lindsay has served as a consultant and an advisory board participant for AbbVie, Astra Zeneca, Bristol Myers Squibb, , Celltrion, Eli Lilly, Engytix, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, MSD, Pfizer, Takeda, and Vifor Pharma; has received speaker fees and sponsorship for academic meetings from AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Pfizer, Tillotts Pharma, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, and Takeda.
Marc Ferrante has received research grants from AbbVie, EG Pharma, Janssen, Pfizer, Takeda, and Viatris; consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Merck Sharp and Dohme, MRM Health, Pfizer, Takeda, and ThermoFisher; and speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare, and Viatris.
Britta Siegmund has received consulting fees from AbbVie, Abivax, Boehringer Ingelheim, BMS, Dr Falk, Endpoint Health, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, and Takeda, and speaker’s fees from AbbVie, AlfaSigma, BMS, CED Service, Dr Falk, Ferring, Galapagos, Janssen, Lilly, MSD, Pfizer, and Takeda.
Qian Cao has served as a steering committee adviser for Bristol Myers Squibb Company, and Janssen Research Development, LLC; and has received research grants from Takeda and Johnson & Johnson.
Stijn van Haaren, Jameson Crowley, Toni Anschutz, and Andrew Garrison are full-time employees of AbbVie and may own AbbVie stock or stock options.
Marla Dubinsky has received consulting and advisory fees from AbbVie, Abivax, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, GSK, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Prometheus Biosciences, Sanofi, Spyre and Takeda
Funding: AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. Medical writing support was provided by Mahesh Chemudupati, PhD of AbbVie. Editorial support was provided by Amy Kuang, PhD of AbbVie.

DURABLE EFFICACY OF RISANKIZUMAB THROUGH WEEK 100 IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE: A POST HOC ANALYSIS FROM PART 2 OF THE SEQUENCE TRIAL

Raja Atreya 1, James O. Lindsay 2, Marc Ferrante 3, Britta Siegmund 4, Qian Cao 5, Stijn Van Haaren 6, Jameson Crowley 6, Toni Anschutz 6, Andrew Garrison 6, Marla C. Dubinsky 7

1 Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

2 Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom

3 University Hospitals Leuven, Leuven, Belgium

4 Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany|||Campus Benjamin Franklin, Berlin, Germany

5 Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China

6 AbbVie Inc, North Chicago, IL, United States

7 Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

New treatments on the horizon for Crohn's disease (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Poster

Standard Poster

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Introduction

Endoscopic healing is an important treatment goal for patients (pts) with Crohn’s disease (CD).¹ Herein, the relationships between endoscopic healing and achievement of long-term patient reported outcomes (PROs) and occurrence of CD-related hospitalization were assessed in pts with moderate to severe CD treated with risankizumab (RZB) maintenance therapy from the FORTIFY trial.

Aims & Methods

In FORTIFY, pts who had clinical response to RZB induction² received 52 weeks (wks) of maintenance therapy (subcutaneous 180mg or 360mg every 8wks) in substudy 1³ and continued receiving RZB as per their treatment assignment in the open-label extension (OLE) substudy 3. This analysis included pts who completed 2 years (y) of RZB in the OLE (cumulative RZB treatment of 3 years including 52wks in substudy 1) (cutoff date: 01MAR2024). Clinically meaningful improvements in PROs were assessed, including Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase in total score), IBDQ remission (total score ≥170-points), improvement in 36-Item Short Survey (SF-36) physical component score (PCS, ≥4.1-points) and mental component summary (MCS, ≥3.9-points), EuroQol-5D questionnaire visual analog scale (EQ-5D-5L VAS; ≥9.2-points), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) response (≥9-points). Exposure-adjusted occurrence of CD-related hospitalizations was also assessed as incidence rates (events/100 patient-y) from OLE wk52 to wk152. The proportion of pts who achieved each outcome at wk152 were compared based on their achievement of wk52 endoscopic response, endoscopic remission, or ulcer-free endoscopy vs not (endpoint definitions in Table footnote) using chi-square testing. Pts with missing outcomes were considered nonresponders. Endoscopies were scored by a central reviewer. Long-term safety of RZB has been reported.²

Results

Of the 257 pts included in the analysis, 134 (52.1%), 99 (38.5%), and 79 (30.7%) pts achieved wk52 endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively. Significantly more pts who achieved wk52 endoscopic response also achieved IBDQ response and remission, SF36 PCS and MCS response, and improvement in FACIT-F and EQ-5D-5L VAS scores at wk152 (P≤.0001 for all comparisons) vs pts who did not achieve wk52 endoscopic response (Table). Similar results were observed for pts who achieved wk52 endoscopic remission (P≤.01) and pts who achieved wk52 ulcer-free endoscopy (P≤.02, except for SF36 MCS response) at wk152. CD-related hospitalizations from wk56 to wk152 were significantly lower for pts who achieved wk52 endoscopic remission and endoscopic response and numerically lower for pts who achieved wk52 ulcer-free endoscopy, vs not.

Parameter	Endoscopic response^a (Yes), N=134	Endoscopic response^a (No), N=123	P value	Endoscopic remission^b (Yes), N=99	Endoscopic remission^b (No), N=158	P value	Ulcer-free endoscopy^c (Yes), N=79	Ulcer-free endoscopy^c (Yes), N=178	P value
PROs at Week 152 (Week 96 of FORTIFY OLE) n/N (%) IBDQ response^d IBDQ remission^e SF36 PCS response^f SF36 MCS response^g EQ-5D-5L VAS^h FACIT-F responseⁱ Exposure adjusted occurrence of CD-related hospitalizations from maintenance week 0 to week 152^j n/N (%) [time in patient-years] incidence rate	100/134 (74.6) 84/134 (62.7) 90/134 (67.2) 80/134 (59.7) 94/134 (70.2) 106/134 (79.1) 6/134 (4.5) [395.0773] 1.52	55/123 (44.7) 46/123 (37.4) 53/123 (43.1) 43/123 (35.0) 54/123 (43.9) 65/123 (52.8) 13/123 (10.6) [257.8864] 5.04	<.0001 <.0001 .0001 <.0001 <.0001 <.0001 .0213	71/99 (71.7) 65/99 (65.7) 67/99 (67.7) 57/99 (57.6) 67/99 (67.7) 77/99 (77.8) 4/99 (4.0) [292.5174] 1.37	84/158 (53.2) 65/158 (41.1) 76/158 (48.1) 66/158 (41.8) 81/158 (51.3) 94/158 (59.5) 15/158 (9.5) [360.4463] 4.16	.0031 .0001 .0021 .0136 .0096 .0025 .0282	60/79 (76.0) 51/79 (64.6) 55/79 (69.6) 45/79 (57.0) 54/79 (68.4) 63/79 (79.8) 5/79 (6.3) [234.1136] 2.14	95/178 (53.4) 79/178 (44.4) 88/178 (49.4) 78/178 (43.8) 94/178 (52.8) 108/178 (60.7) 14/178 (7.9) [418.8501] 3.34	.0006 .0028 .0027 .0517 .0200 .0028 .3561
Abbreviations: BL, baseline; CD, Crohn’s disease; EQ-5D-5L VAS, EuroQol-5D questionnaire visual analog scale; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; IBDQ, inflammatory bowel disease questionnaire; MCS, mental component score; OLE, open-label extension; PCS, physical component score; PROs, patient reported outcomes; SES-CD, Simple Endoscopic Score for CD; SF-36, 36-Item Short Form Survey. ^aEndoscopic response: decrease in the SES-CD > 50% from induction BL (or for patients with isolated ileal disease and a BL SES-CD = 4, ≥ 2 point reduction from induction BL). ^bEndoscopic remission: SES-CD ≤ 4, ≥ 2-point reduction from BL, and no subscore > 1 in any individual variable. ^cUlcer-free endoscopy: SES-CD ulcerated surface subscore of 0 in patients with SES-CD ulcerated surface subscore ≥ 1 at induction BL. ^dIBDQ response: ≥ 16-point IBDQ total point improvement from the induction BL. ^eIBDQ remission: IBDQ total score ≥ 170 points. ^fSF-36 PCS response: change ≥ 4.1 from BL. ^gSF-36 MCS response: change ≥ 3.9 from BL. ^hEQ-5D-5L VAS: change ≥ 9.2 from BL. ⁱFACIT-F response: change ≥ 9 from BL. ^jIncidence rate differences (95% CI and P value) between the comparison groups were based on the normal approximation to poisson distribution. Bold font denotes a P value ≤ .05.

Conclusion

A significantly greater proportion of pts achieved 3y sustained improvement in PROs when they achieved endoscopic outcomes at 52wks of RZB maintenance treatment. Achievement of endoscopic outcomes at 52wks also resulted in fewer CD-related hospitalizations through 152wks when continuing active therapy, pointing to favorable long-term outcomes of disease.

References

Turner D, et al. Gastroenterology. 2021;160:1570-83.
Ferrante M, et al. J Crohns Colitis. 2021; 15(12):2001-2010.

Disclosure

Christopher Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer.
Brian G Feagan has served as a consultant or received speaker’s fees from Abbott/AbbVie, ActoGeniX, Akros, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharmaceuticals, gIcare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharmaceuticals, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Kyowa Hakko Kirin Co, Lexicon, Lilly, Lycera, Merck, Mesoblast, Millennium, Nektar, Nestlé, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Receptos, Roche/Genentech, Salix Pharmaceuticals, Serono, Shire, Sigmoid Pharma, Synergy Pharmaceuticals, Takeda, Teva Pharmaceuticals, TiGenix, Tillotts, UCB, Vertex Pharmaceuticals, VHsquared, Warner Chilcott, Wyeth, Zealand Pharma, and Zyngenia, and has received research support from Abbott/AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Millennium, Pfizer, Receptos, Roche/Genentech, Sanofi, Santarus, Tillotts, and UCB.
Peter Bossuyt received financial support for research from AbbVie, Amgen, Celltrion, Mylan, Pfizer, and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly, and Takeda; and advisory board fees from AbbVie, Arena Pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros.
Vipul Jairath has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi.
Namita Joshi, Nidhi Shukla, Kristina Kligys, Ari Stromberg,andJameson Crowley are full-time employees/contractor of AbbVie and may own AbbVie stock or options.
Acknowledgments
AbbVie funded this study (NCT03105102) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial.
Medical writing support was provided by Stephanie Parsons, PhD, an employee of AbbVie. Editorial support was provided by Amy Kuang, an employee of AbbVie.

THE ASSOCIATION BETWEEN ENDOSCOPIC HEALING AND LONG-TERM PATIENT REPORTED OUTCOMES AND HOSPITALIZATION IN PATIENTS WITH MODERATE TO SEVERE CROHN’S DISEASE AFTER 3 YEARS OF RISANKIZUMAB MAINTENANCE TREATMENT: POST HOC ANALYSIS OF THE PHASE 3 FORTIFY TRIAL

Christopher Ma 1, Namita Joshi 2, Brian G. Feagan 3, Peter Bossuyt 4, Nidhi Shukla 2, Kristina Kligys 2, Ari Stromberg 2, Jameson Crowley 2, Vipul Jairath 5

1 University of Calgary, Calgary, Canada|||University of Calgary, Calgary, Canada

2 AbbVie, North Chicago, United States

3 Alimentiv Inc., London, Canada

4 Imelda General Hospital, Bonheiden, Belgium

5 Western University, London, Canada|||Western University, London, Canada

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Predicting outcomes in IBD (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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MICROPLASTIC-INDUCED ALTERATIONS IN GUT MICROBIOME AND METABOLISM: INSIGHTS FROM AN EX VIVO BIOREACTOR MODEL

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Introduction

Microplastic particles (MPs), defined as plastic fragments smaller than 5 mm, are pervasive pollutants that accumulate in ecosystems and the human food chain (1). Literature points at various health risks, including the induction of carcinogenesis (2). Emerging evidence from animal models (3) suggests that MPs may influence the gut microbiome, but the impact on the human gut microbiome remains poorly understood.

Aims & Methods

This study aimed to evaluate how various MP types influence gut microbial composition and metabolism using an ex vivo bioreactor model, with a focus on exploring potential carcinogenic effects arising from MP–microbiome interactions.
Stool samples from healthy donors were used to inoculate bioreactor cultures, which were maintained under anaerobic conditions for five days with daily nutrient feeding. These cultures were exposed to five common MP types—polystyrene (PS), polypropylene (PP), low-density polyethylene (LDPE), poly(methyl methacrylate) (PMMA), and polyethylene terephthalate (PET)—at concentrations mimicking both estimated human exposure (4) and higher doses to assess dose-dependence. Cell viability and total bacterial counts, as well as culture pH, were measured throughout the experiment. To further explore potential microbiome and metabolic alterations, 16S rRNA gene sequencing and targeted metabolomics were performed.

Results

MP exposure did not lead to significant changes in total or viable bacterial cell counts. However, MP-treated cultures exhibited a consistent and significant decrease in pH compared to controls, suggesting changes in microbial metabolic activity. Microbiome sequencing revealed plastic-type-dependent alterations in microbial composition, with certain bacterial taxa increasing or decreasing in abundance depending on the MP type. These shifts occurred across multiple genera within diverse families, including Lachnospiraceae, Oscillospiraceae, Enterobacteriaceae, and Ruminococcaceae, with the majority of changes occurring withing the phylum Bacillota. These compositional changes were accompanied by shifts in the metabolomic profiles, some of which correlated with the observed pH changes. Several plastic types induced changes in valeric acid levels, while individual MP types were associated with alterations in distinct metabolites such as uracil, lactic acid, and acetic acid.

Conclusion

This study demonstrates that MPs can affect gut microbial activity and metabolism without significantly altering overall bacterial abundance in the short term. The variation in microbiome response across plastic types highlights the complexity of MP-microbiome interactions. Changes in faecal pH are known to be associated with various gastrointestinal diseases (5). Interestingly, some of the MP-induced changes in microbial composition resembled patterns linked to diseases such as depression and colorectal cancer. In contrast, other changes showed patterns that differed from those typically associated with conditions like Parkinson’s disease and irritable bowel syndrome, highlighting the complexity of these associations and the dependency on the context. The bioreactor model provided a controlled environment for identifying direct MP-microbiome interactions; however, in humans, additional factors like diet, immune response, and individual microbiome variations play a role in determining long-term effects. Exposure duration may also play a critical role in shaping the extent and nature of microbiome alterations (6), underscoring the need for further research into the effects of chronic MP exposure and associated health risks.

References

(1) Mamun, A. A., Prasetya, T. A. E., Dewi, I. R., & Ahmad, M. (2023). Microplastics in human food chains: Food becoming a threat to health safety. The Science of the total environment, 858(Pt 1), 159834. https://doi.org/10.1016/j.scitotenv.2022.159834
(2) Kumar, R., Manna, C., Padha, S., Verma, A., Sharma, P., Dhar, A., Ghosh, A., & Bhattacharya, P. (2022). Micro(nano)plastics pollution and human health: How plastics can induce carcinogenesis to humans?. Chemosphere, 298, 134267. https://doi.org/10.1016/j.chemosphere.2022.134267
(3) Hirt, N., & Body-Malapel, M. (2020). Immunotoxicity and intestinal effects of nano- and microplastics: a review of the literature. Particle and fibre toxicology, 17(1), 57. https://doi.org/10.1186/s12989-020-00387-7
(4) Senathirajah, K., Attwood, S., Bhagwat, G., Carbery, M., Wilson, S., & Palanisami, T. (2021). Estimation of the mass of microplastics ingested - A pivotal first step towards human health risk assessment. Journal of hazardous materials, 404(Pt B), 124004. https://doi.org/10.1016/j.jhazmat.2020.124004
(5) Yamamura, R., Inoue, K. Y., Nishino, K., & Yamasaki, S. (2023). Intestinal and fecal pH in human health. Frontiers in Microbiomes, 2, 1192316.
(6) Yin, L., Yang, M., Teng, A., Ni, C., Wang, P., & Tang, S. (2025). Unraveling Microplastic Effects on Gut Microbiota across Various Animals Using Machine Learning. ACS nano, 19(1), 369–380. https://doi.org/10.1021/acsnano.4c07885

MICROPLASTIC-INDUCED ALTERATIONS IN GUT MICROBIOME AND METABOLISM: INSIGHTS FROM AN EX VIVO BIOREACTOR MODEL

Christian Pacher-Deutsch 1, Kristina Žukauskaitė 1, Cigdem Akar 2, Maximilian Nepel 2, Lukas Kogler 3, Hansjörg Habisch 2, Serena Ducoli 4, Stefania Federici 4, Tobias Madl 5, Verena Pichler 6, Angela Horvath 1, Vanessa Stadlbauer 7

1 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||Medical University of Graz, Graz, Austria

2 Medical University of Graz, Graz, Austria

3 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||University of Vienna, Vienna, Austria|||Medical University of Vienna, Vienna, Austria

4 University of Brescia, Brescia, Italy

5 Medical University of Graz, Graz, Austria|||BioTechMed-Graz, Graz, Austria

6 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||University of Vienna, Vienna, Austria

7 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||Medical University of Graz, Graz, Austria|||BioTechMed-Graz, Graz, Austria

Event

UEG Week Berlin 2025

Topics

Gut Microbiota Colorectal

Submission format

Abstract

Session

The gut ecosystem: From pathogenesis to treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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