Evidence map›Paper›PMID 33225894›Full record

ArticleBMC microbiology2020

Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells.

Amy M Ehrlich, Alline R Pacheco, Bethany M Henrick, Diana Taft, Gege Xu, M Nazmul Huda, Darya Mishchuk, Michael L Goodson, Carolyn Slupsky, Daniela Barile and 4 more

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

Article in BMC microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
173citing papers in PubMed, 2 pooled it
9.8field-weighted citation impact, top 1% 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

173 citing papers in PubMed, 2 syntheses or guidelines pooled it, 275 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Efficacy and Safety ofNutrients · 2025
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  17. Bidirectional Modulation of the Tumor Immune Microenvironment by Gut Microbiota-Derived Indoles: Mechanisms and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  18. Engineered probioticScience advances · 2026
    Article
  19. Review
  20. Review

113 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 2 countries.

Amy M EhrlichDepartment of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Alline R PachecoFoods for Health Institute, University of California, Davis, CA, USA.
Bethany M HenrickDepartment of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Diana TaftFoods for Health Institute, University of California, Davis, CA, USA.
Gege XuDepartment of Chemistry, University of California, Davis, CA, USA.
M Nazmul HudaEnteric and Respiratory Infections Unit, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Darya MishchukDepartment of Food Science and Technology, University of CA, Davis, CA, USA.
Michael L GoodsonDepartment of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Carolyn SlupskyDepartment of Food Science and Technology, University of CA, Davis, CA, USA.
Daniela BarileFoods for Health Institute, University of California, Davis, CA, USA.
Carlito B LebrillaDepartment of Chemistry, University of California, Davis, CA, USA.
Charles B StephensenUS Department of Agriculture, Western Human Nutrition Research Center, Davis, CA, USA.
David A MillsFoods for Health Institute, University of California, Davis, CA, USA.
Helen E RaybouldDepartment of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA. heraybould@ucdavis.edu.ORCID 0000-0002-7501-8091
University of California, Davis · USInternational Centre for Diarrhoeal Disease Research · BDWestern Human Nutrition Research Center · US

Funding

Activation of probiotic bifidobacteria by milk glyansR01AT008759 · NCCIH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GERMAN, BRUCE, LEBRILLA, CARLITO B · 2014 to 2018
$4.2M
Mechanism of Activation of Probiotic Bifidobacteria by Prebiotic Milk GlycansR01AT007079 · NCCIH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GERMAN, BRUCE, LEBRILLA, CARLITO B · 2012 to 2016
$2.2M
Activation of Host-Probiotic Communication by Prebiotic Milk OligosaccharidesR21AT006180 · NCCIH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MILLS, DAVID ANDREW, RAYBOULD, HELEN E · 2011 to 2012
$421k
Effects of Bifidobacterium Dominance on the Infant MicrobiomeF32HD093185 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI TAFT, DIANA HAZARD · 2017 to 2020
$218k
Agricultural Research Service 2032-53000-001-00-DNational Institutes of Health (US) AT006180NCCIH NIH HHS R01 AT007079NCCIH NIH HHS R01 AT008759NCCIH NIH HHS R21 AT006180NICHD NIH HHS F32 HD093185NIH HHS AT007079NIH HHS AT008759World Health Organization 2010168947
6 · The paper itself

Abstract

backgroundBifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host.

resultsIn a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2-related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors.

conclusionsThese findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway.

Indexed as

MicrobiotaAnimalsAnti-Inflammatory AgentsBifidobacteriumCell LineEndotoxinsEpithelial CellsFecesGastrointestinal TractHumansIndolesInfantInterleukin-8LactoseMacrophage ActivationMiceAnti-Inflammatory AgentsEndotoxinsindole-3-lactic acidIndolesInterleukin-8LactoseNF-E2-Related Factor 2OligosaccharidesReceptors, Aryl HydrocarbonAryl-hydrocarbon receptorIndole-3-lactic acidMilk oligosaccharidesNuclear factor erythroid 2–related factor 2

Identifiers

PMID33225894
PMCPMC7681996
OpenAlexW3106931136

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.