Evidence map›Paper›PMID 35505245›Full record

ArticleNature microbiology2022

Clostridium sporogenes uses reductive Stickland metabolism in the gut to generate ATP and produce circulating metabolites.

Yuanyuan Liu, Haoqing Chen, William Van Treuren, Bi-Huei Hou, Steven K Higginbottom, Dylan Dodd

Open access · greenAbstract read
In one paragraph

Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
7.0field-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

57 citing papers in PubMed, 91 citations in OpenAlex.

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  9. Apple Pomace Fermented with Non-International journal of molecular sciences · 2026
    Article
  10. pH regulates gut bacterial tryptophan metabolism.NPJ biofilms and microbiomes · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Yuanyuan LiuDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Haoqing ChenDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4290-6092
William Van TreurenDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Bi-Huei HouDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Steven K HigginbottomDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Dylan DoddDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA. ddodd2@stanford.edu.ORCID http://orcid.org/0000-0001-6210-6239
Stanford University · USStanford Medicine · US

Funding

Microbiota-based probiotics to treat inborn errors in metabolismR01AT011396 · NCCIH · STANFORD UNIVERSITY · PI Dylan Dodd · 2022 to 2026
$2.9M
Physiology of bacterial metabolism in the human gut microbiomeR35GM142873 · NIGMS · STANFORD UNIVERSITY · PI DODD, DYLAN · 2021 to 2025
$2.0M
Modulation of gut bacteria-derived host metabolitesK08DK110335 · NIDDK · STANFORD UNIVERSITY · PI DODD, DYLAN · 2018 to 2021
$573k
NCCIH NIH HHS R01 AT011396NIDDK NIH HHS K08 DK110335NIGMS NIH HHS R35 GM142873
6 · The paper itself

Abstract

Gut bacteria face a key problem in how they capture enough energy to sustain their growth and physiology. The gut bacterium Clostridium sporogenes obtains its energy by utilizing amino acids in pairs, coupling the oxidation of one to the reduction of another-the Stickland reaction. Oxidative pathways produce ATP via substrate-level phosphorylation, whereas reductive pathways are thought to balance redox. In the present study, we investigated whether these reductive pathways are also linked to energy generation and the production of microbial metabolites that may circulate and impact host physiology. Using metabolomics, we find that, during growth in vitro, C. sporogenes produces 15 metabolites, 13 of which are present in the gut of C. sporogenes-colonized mice. Four of these compounds are reductive Stickland metabolites that circulate in the blood of gnotobiotic mice and are also detected in plasma from healthy humans. Gene clusters for reductive Stickland pathways suggest involvement of electron transfer proteins, and experiments in vitro demonstrate that reductive metabolism is coupled to ATP formation and not just redox balance. Genetic analysis points to the broadly conserved Rnf complex as a key coupling site for energy transduction. Rnf complex mutants show aberrant amino acid metabolism in a defined medium and are attenuated for growth in the mouse gut, demonstrating a role of the Rnf complex in Stickland metabolism and gut colonization. Our findings reveal that the production of circulating metabolites by a commensal bacterium within the host gut is linked to an ATP-yielding redox process.

Indexed as

ClostridiumMetabolomicsAdenosine TriphosphateAnimalsBacteriaFermentationMiceAdenosine Triphosphate

Identifiers

PMID35505245
PMCPMC9089323
OpenAlexW4225424738

What OpenQuestion holds

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Registered trials

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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.