Evidence map›Paper›PMID 29797022›Full record

ArticleDiabetologia2018

The DPP-4 inhibitor vildagliptin impacts the gut microbiota and prevents disruption of intestinal homeostasis induced by a Western diet in mice.

Marta Olivares, Audrey M Neyrinck, Sarah A Pötgens, Martin Beaumont, Nuria Salazar, Patrice D Cani, Laure B Bindels, Nathalie M Delzenne

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 3 countries.

Marta OlivaresMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73 av. E. Mounier, Box B1.73.11, 1200, Brussels, Belgium.ORCID http://orcid.org/0000-0002-7966-2781
Audrey M NeyrinckMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73 av. E. Mounier, Box B1.73.11, 1200, Brussels, Belgium.
Sarah A PötgensMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73 av. E. Mounier, Box B1.73.11, 1200, Brussels, Belgium.
Martin BeaumontMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73 av. E. Mounier, Box B1.73.11, 1200, Brussels, Belgium.
Nuria SalazarDepartment of Microbiology and Biochemistry, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Spain.
Patrice D CaniMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73 av. E. Mounier, Box B1.73.11, 1200, Brussels, Belgium.
Laure B BindelsMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73 av. E. Mounier, Box B1.73.11, 1200, Brussels, Belgium.
Nathalie M DelzenneMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73 av. E. Mounier, Box B1.73.11, 1200, Brussels, Belgium. nathalie.delzenne@uclouvain.be.
Solvay (Belgium) · BEConsejo Superior de Investigaciones Científicas · ES

Funding

European Research Council (ERC) ERC Starting Grant 336452-ENIGMOFP7 EU grant (MyNewGut) EU grant 613979FP7 People: Marie-Curie Actions MOVE IN Louvain Post-doctoral Fellowship co-fundedFRFS-WELBIO WELBIO-CGR-2017Funds Baillet Latour Grant for Medical Research 2015Ministerio de Economía y Competitividad Juan de la Cierva post-doctoral contract
6 · The paper itself

Abstract

aims/hypothesisDipeptidyl peptidase 4 (DPP-4) inhibitors are agents designed to increase the half-life of incretins. Although they are administered orally, little is known about their effects on the gut microbiota and functions, despite the fact that some bacteria present in the gut microbiota exhibit DPP-4-like activity. Our objective was to study the impact of the DPP-4 inhibitor vildagliptin on gut functions and the intestinal ecosystem in a murine model of obesity induced by a Western diet (WD).

methodsTwenty seven male C57BL/6J mice were randomised to receive a control diet, a WD (45% kJ from fat and 17% kJ from sucrose) or a WD + vildagliptin (0.6 mg/ml in drinking water) for 8 weeks.

resultsVildagliptin significantly reduced DPP-4 activity in the caecal content and faeces. Vildagliptin impacted on the composition of the gut microbiota and its metabolic activity. It mainly decreased Oscillibacter spp. (a direct effect independent of DPP-4 activity was shown on cultured O. valericigenes), increased Lactobacillus spp. and propionate, and reduced the ligands of Toll-like receptors 2 and 4. Vildagliptin protected against the reductions in crypt depth and ileal expression of antimicrobial peptides induced by the WD. In the liver, the expression of immune cell populations (Cd3g and Cd11c [also known as Itgax]) and cytokines was decreased in the WD + vildagliptin-fed mice compared with the WD-fed group. Ex vivo exposure of precision-cut liver slices to vildagliptin showed that this response was not related to a direct effect of the drug on the liver tissue. CONCLUSIONS/

interpretationOur study is the first to consider the DPP-4-like activity of the gut microbiota as a target of DPP-4 inhibition. We propose that vildagliptin exerts beneficial effects at the intestinal level in association with modulation of gut microbiota, with consequences for hepatic immunity. If relevant in humans, this could open new therapeutic uses of DPP-4 inhibition to tackle gut dysfunctions in different pathophysiological contexts. DATA AVAILABILITY: The sequences used for analysis can be found in the MG-RAST database under the project name MYNEWGUT3.

Indexed as

Gastrointestinal MicrobiomeAnimalsCytokinesDiet, WesternDipeptidyl-Peptidase IV InhibitorsEcosystemFatty Acids, VolatileGene Expression ProfilingHomeostasisHypoglycemic AgentsInflammationIntestinesLiverMaleMiceMice, Inbred C57BLCytokinesDipeptidyl-Peptidase IV InhibitorsFatty Acids, VolatileHypoglycemic AgentsVildagliptinAntimicrobial peptidesDPP-4 activityGut–liver axisGut microbiotaVildagliptinWestern diet

Identifiers

PMID29797022
PMCPMC6061172
OpenAlexW2804589304

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.