Cystic fibrosis related diabetes has a distinct gut microbiome dysbiosis

R. Marsh; D. Sills; H.A. Saumtally; J.M. Tricker; W. Cheung; D. Arends; A. Párniczky; K. Ocskay; D. Peckham; R.C. Spiller; L. Marciani; D.G. Downey; I.D. Stewart; T.M. Monaghan; A.R. Smyth; D.W. Rivett; C. van der Gast

doi:10.1016/S1569-1993(26)00288-2

Abstract

Objectives: Gut microbiome dysbiosis is common across people with CF
(pwCF) and may be further exacerbated with additional GI co-abnormalities.
CF-related diabetes (CFRD) is a prominent comorbidity in pwCF, yet its
impact upon the gut microbiome is not known. We investigated the gut
microbiota, metabolome, and lipidome across pwCF with/without CFRD and
control participants.

Methods: Stool samples from pwCF with (n=33) and without (n=33) CFRD,
alongside controls (n=19), were subjected to full-length 16S rRNA microbiota sequencing. LC/MS analyses (n=57) were conducted on CF stool
samples to investigate differences in metabolite and lipid composition.
Multivariate approaches and generalised linear models were used to investigate relationships with clinical data.

Results: Microbiota diversity and composition significantly differed between
controls and pwCF, including across CF groups (q<0.05). A higher prevalence
of gut pathobionts, alongside reduced prevalence of beneficial taxa was
observed in CFRD. Strikingly, an increased prevalence of lung pathogens
(including Pseudomonas aeruginosa and Staphylococcus aureus) was also
observed in CFRD. Additional clinical factors significantly explained microbiota variation. Modulator therapy was not significant. Importantly, after
adjusting for such confounders, CFRD remained a significant driver of microbiota composition across pwCF (q=0.024). Lipidomic profiles also significantly
clustered based on the presence of CFRD following covariate adjustment
(q=0.030). Immunomodulatory lipid species, including increased hexosylceramides (q=0.030) and oxidised phosphatidylcholines (q=0.073), alongside decreased sulphonolipids (q=0.054), were observed across the CFRD group.

Conclusions: We demonstrate for the first time a distinct and worse
microbiome dysbiosis in CFRD. The causative nature and clinical consequences of such host-microbe alterations warrant additional research of the
CF gut utilising multiomics approaches.

Original language	English
Article number	EPS6.03
Pages (from-to)	S50-S50
Number of pages	1
Journal	Journal of Cystic Fibrosis
Volume	25
Issue number	Supplement 1
Early online date	2 Jun 2026
DOIs	https://doi.org/10.1016/S1569-1993(26)00288-2
Publication status	Published - Jun 2026
Event	49th European Cystic Fibrosis Conference - Centro de Congressos de Lisboa (CCL), Lisbon, Portugal Duration: 3 Jun 2026 → 6 Jun 2026

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/S1569-1993(26)00288-2

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Marsh, R., Sills, D., Saumtally, H. A., Tricker, J. M., Cheung, W., Arends, D., Párniczky, A., Ocskay, K., Peckham, D., Spiller, R. C., Marciani, L., Downey, D. G., Stewart, I. D., Monaghan, T. M., Smyth, A. R., Rivett, D. W., & van der Gast, C. (2026). Cystic fibrosis related diabetes has a distinct gut microbiome dysbiosis. Journal of Cystic Fibrosis, 25(Supplement 1), S50-S50. Article EPS6.03. https://doi.org/10.1016/S1569-1993(26)00288-2

@article{342144d830ee4da6a69d45d5d8c483b6,

title = "Cystic fibrosis related diabetes has a distinct gut microbiome dysbiosis",

abstract = "Objectives: Gut microbiome dysbiosis is common across people with CF (pwCF) and may be further exacerbated with additional GI co-abnormalities. CF-related diabetes (CFRD) is a prominent comorbidity in pwCF, yet its impact upon the gut microbiome is not known. We investigated the gut microbiota, metabolome, and lipidome across pwCF with/without CFRD and control participants. Methods: Stool samples from pwCF with (n=33) and without (n=33) CFRD, alongside controls (n=19), were subjected to full-length 16S rRNA microbiota sequencing. LC/MS analyses (n=57) were conducted on CF stool samples to investigate differences in metabolite and lipid composition. Multivariate approaches and generalised linear models were used to investigate relationships with clinical data. Results: Microbiota diversity and composition significantly differed between controls and pwCF, including across CF groups (q<0.05). A higher prevalence of gut pathobionts, alongside reduced prevalence of beneficial taxa was observed in CFRD. Strikingly, an increased prevalence of lung pathogens (including Pseudomonas aeruginosa and Staphylococcus aureus) was also observed in CFRD. Additional clinical factors significantly explained microbiota variation. Modulator therapy was not significant. Importantly, after adjusting for such confounders, CFRD remained a significant driver of microbiota composition across pwCF (q=0.024). Lipidomic profiles also significantly clustered based on the presence of CFRD following covariate adjustment (q=0.030). Immunomodulatory lipid species, including increased hexosylceramides (q=0.030) and oxidised phosphatidylcholines (q=0.073), alongside decreased sulphonolipids (q=0.054), were observed across the CFRD group. Conclusions: We demonstrate for the first time a distinct and worse microbiome dysbiosis in CFRD. The causative nature and clinical consequences of such host-microbe alterations warrant additional research of the CF gut utilising multiomics approaches.",

author = "R. Marsh and D. Sills and H.A. Saumtally and J.M. Tricker and W. Cheung and D. Arends and A. P{\'a}rniczky and K. Ocskay and D. Peckham and R.C. Spiller and L. Marciani and D.G. Downey and I.D. Stewart and T.M. Monaghan and A.R. Smyth and D.W. Rivett and \{van der Gast\}, C.",

year = "2026",

month = jun,

doi = "10.1016/S1569-1993(26)00288-2",

language = "English",

volume = "25",

pages = "S50--S50",

journal = "Journal of Cystic Fibrosis",

issn = "1569-1993",

publisher = "Elsevier",

number = "Supplement 1",

note = "49th European Cystic Fibrosis Conference, \#ECFS2026 ; Conference date: 03-06-2026 Through 06-06-2026",

}

Marsh, R, Sills, D, Saumtally, HA, Tricker, JM , Cheung, W , Arends, D, Párniczky, A, Ocskay, K, Peckham, D, Spiller, RC, Marciani, L, Downey, DG, Stewart, ID, Monaghan, TM, Smyth, AR, Rivett, DW & van der Gast, C 2026, 'Cystic fibrosis related diabetes has a distinct gut microbiome dysbiosis', Journal of Cystic Fibrosis, vol. 25, no. Supplement 1, EPS6.03, pp. S50-S50. https://doi.org/10.1016/S1569-1993(26)00288-2

TY - JOUR

T1 - Cystic fibrosis related diabetes has a distinct gut microbiome dysbiosis

AU - Marsh, R.

AU - Sills, D.

AU - Saumtally, H.A.

AU - Tricker, J.M.

AU - Cheung, W.

AU - Arends, D.

AU - Párniczky, A.

AU - Ocskay, K.

AU - Peckham, D.

AU - Spiller, R.C.

AU - Marciani, L.

AU - Downey, D.G.

AU - Stewart, I.D.

AU - Monaghan, T.M.

AU - Smyth, A.R.

AU - Rivett, D.W.

AU - van der Gast, C.

PY - 2026/6

Y1 - 2026/6

N2 - Objectives: Gut microbiome dysbiosis is common across people with CF (pwCF) and may be further exacerbated with additional GI co-abnormalities. CF-related diabetes (CFRD) is a prominent comorbidity in pwCF, yet its impact upon the gut microbiome is not known. We investigated the gut microbiota, metabolome, and lipidome across pwCF with/without CFRD and control participants. Methods: Stool samples from pwCF with (n=33) and without (n=33) CFRD, alongside controls (n=19), were subjected to full-length 16S rRNA microbiota sequencing. LC/MS analyses (n=57) were conducted on CF stool samples to investigate differences in metabolite and lipid composition. Multivariate approaches and generalised linear models were used to investigate relationships with clinical data. Results: Microbiota diversity and composition significantly differed between controls and pwCF, including across CF groups (q<0.05). A higher prevalence of gut pathobionts, alongside reduced prevalence of beneficial taxa was observed in CFRD. Strikingly, an increased prevalence of lung pathogens (including Pseudomonas aeruginosa and Staphylococcus aureus) was also observed in CFRD. Additional clinical factors significantly explained microbiota variation. Modulator therapy was not significant. Importantly, after adjusting for such confounders, CFRD remained a significant driver of microbiota composition across pwCF (q=0.024). Lipidomic profiles also significantly clustered based on the presence of CFRD following covariate adjustment (q=0.030). Immunomodulatory lipid species, including increased hexosylceramides (q=0.030) and oxidised phosphatidylcholines (q=0.073), alongside decreased sulphonolipids (q=0.054), were observed across the CFRD group. Conclusions: We demonstrate for the first time a distinct and worse microbiome dysbiosis in CFRD. The causative nature and clinical consequences of such host-microbe alterations warrant additional research of the CF gut utilising multiomics approaches.

AB - Objectives: Gut microbiome dysbiosis is common across people with CF (pwCF) and may be further exacerbated with additional GI co-abnormalities. CF-related diabetes (CFRD) is a prominent comorbidity in pwCF, yet its impact upon the gut microbiome is not known. We investigated the gut microbiota, metabolome, and lipidome across pwCF with/without CFRD and control participants. Methods: Stool samples from pwCF with (n=33) and without (n=33) CFRD, alongside controls (n=19), were subjected to full-length 16S rRNA microbiota sequencing. LC/MS analyses (n=57) were conducted on CF stool samples to investigate differences in metabolite and lipid composition. Multivariate approaches and generalised linear models were used to investigate relationships with clinical data. Results: Microbiota diversity and composition significantly differed between controls and pwCF, including across CF groups (q<0.05). A higher prevalence of gut pathobionts, alongside reduced prevalence of beneficial taxa was observed in CFRD. Strikingly, an increased prevalence of lung pathogens (including Pseudomonas aeruginosa and Staphylococcus aureus) was also observed in CFRD. Additional clinical factors significantly explained microbiota variation. Modulator therapy was not significant. Importantly, after adjusting for such confounders, CFRD remained a significant driver of microbiota composition across pwCF (q=0.024). Lipidomic profiles also significantly clustered based on the presence of CFRD following covariate adjustment (q=0.030). Immunomodulatory lipid species, including increased hexosylceramides (q=0.030) and oxidised phosphatidylcholines (q=0.073), alongside decreased sulphonolipids (q=0.054), were observed across the CFRD group. Conclusions: We demonstrate for the first time a distinct and worse microbiome dysbiosis in CFRD. The causative nature and clinical consequences of such host-microbe alterations warrant additional research of the CF gut utilising multiomics approaches.

U2 - 10.1016/S1569-1993(26)00288-2

DO - 10.1016/S1569-1993(26)00288-2

M3 - Meeting Abstract

SN - 1569-1993

VL - 25

SP - S50-S50

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - Supplement 1

M1 - EPS6.03

T2 - 49th European Cystic Fibrosis Conference

Y2 - 3 June 2026 through 6 June 2026

ER -

Cystic fibrosis related diabetes has a distinct gut microbiome dysbiosis

Abstract

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