Evidence map›Paper›PMID 42530605›Full record

ArticleJournal of gastroenterology2026

Tofogliflozin alters amino acid metabolism in gut microbiota linked to hepatic transcriptomic signatures in MASLD.

Kohei Yasuda, Noriho Iida, Yumie Takeshita, Yusuke Masuo, Masao Honda, Toshinari Takamura, Taro Yamashita

Registry-linked trialAbstract read
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In one paragraph

Article in Journal of gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02649465 (Pleiotropic Effects and Safety of Sodium Glucose Co-transporter 2 Inhibitor Versus Sulfonylurea in Patients With Type 2 Diabetes and Non-alcoholic Fatty Liver), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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.

NCT02649465 phase4completednot on this map

Pleiotropic Effects and Safety of Sodium Glucose Co-transporter 2 Inhibitor Versus Sulfonylurea in Patients With Type 2 Diabetes and Non-alcoholic Fatty Liver

TypeinterventionalSponsorKanazawa UniversityRan2015 to 2021Enrolled40ConditionsNon-alcoholic Fatty Liver DiseaseArmsTofogliflozin, Glimepiride
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Kohei YasudaDepartment of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Takara-Machi 13-1, Kanazawa, Ishikawa, 920-8641, Japan.
Noriho IidaDepartment of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Takara-Machi 13-1, Kanazawa, Ishikawa, 920-8641, Japan. niida@m-kanazawa.jp.ORCID http://orcid.org/0000-0002-2917-5053
Yumie TakeshitaDepartment of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
Yusuke MasuoFaculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
Masao HondaDepartment of Advanced Medical Technology, Graduate School of Health Medicine, Kanazawa University, Kanazawa, Japan.
Toshinari TakamuraDepartment of Endocrinology and Metabolism, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
Taro YamashitaDepartment of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Takara-Machi 13-1, Kanazawa, Ishikawa, 920-8641, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA deeper understanding of the relationship between dysbiotic gut microbiota and liver tissue-level molecular and histopathological phenotypes in metabolic dysfunction-associated steatotic liver disease (MASLD) remains needed. We aimed to characterize the associations between gut microbial metabolic functions and treatment responses in participants with MASLD.

methodsWe performed a prespecified sub-analysis of a randomized controlled trial comparing the sodium-glucose cotransporter 2 inhibitor (SGLT2i) tofogliflozin and the sulfonylurea (SU) glimepiride in participants with MASLD and type 2 diabetes (ClinicalTrials.gov NCT02649465). Fecal whole-genome shotgun metagenomics, liver RNA sequencing, serum profiling, and histopathological assessments were integrated to investigate microbiota-host interactions.

resultsMicrobial metabolic pathways, rather than taxonomic composition, differed significantly between participants with MASLD and healthy controls. Among the altered microbial pathways, amino acid metabolism emerged as a prominent functional category and was selected for further investigation. Pathways related to amino acid metabolism, particularly phenylalanine metabolism, exhibited opposing patterns: phenylalanine degradation was enriched in MASLD and positively correlated with liver fibrosis scores, whereas phenylalanine biosynthesis inversely correlated with fibrosis severity. Microbial phenylalanine degradation was positively associated with 28 hepatic pathways, including the non-alcoholic fatty liver disease (NAFLD) pathway, in which mitochondria-associated genes were core-enriched. Both SGLT2i and SU treatments improved NAFLD activity scores and altered microbial metabolic pathways without significantly changing microbial species composition. Notably, SGLT2i increased phenylalanine biosynthesis pathways, which were inversely associated with liver fibrosis.

conclusionsGut microbial amino acid metabolism, particularly phenylalanine metabolism, is closely linked to liver fibrosis and molecular pathways in MASLD. Modulation of microbial metabolic functions may represent a promising therapeutic strategy beyond changes in microbial composition.

Indexed as

Amino acidsMASHMASLDMetagenomePhenylalanine

Identifiers

PMID42530605

What Socratic holds

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Registered trials

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 Socratic graph.