ArticlePloS one2012
Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05026333 (Pilot Study Aimed to Determine the Optimal Design for the UCLA/Danone Probiotic Intervention Study Related to Stress), which is not on this map. Cited by 251 papers, 5 of them syntheses that pooled 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.
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.
Pilot Study Aimed to Determine the Optimal Design for the UCLA/Danone Probiotic Intervention Study Related to Stress
Who cites it
251 citing papers in PubMed, 5 syntheses or guidelines pooled it, 482 citations in OpenAlex.
- STROBE-causal machine learning for the human microbiome: systematic review on methodological innovations and validation frameworks.Frontiers in microbiology · 2026Pooled it
- Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.Microbiology spectrum · 2023Pooled it
- Pooled it
- Oxidative stress tolerance and antioxidant capacity of lactic acid bacteria as probiotic: a systematic review.Gut microbes · 2020Pooled it
- Probiotic supplementation in children with cystic fibrosis-a systematic review.European journal of pediatrics · 2016Pooled it
- Trial
- Genomic, phenotypic, and clinical safety of Limosilactobacillus reuteri ATCC PTA 4659.Journal of industrial microbiology & biotechnology · 2023Trial
- Article
- Targeting the gut microbiome: an integrated probiotic and prebiotic strategy for polycystic ovary syndrome management.Journal of ovarian research · 2026Review
- Unraveling the gut microbiota-brain axis: Mechanisms, pathophysiology, and therapeutic opportunities.iScience · 2026Review
- Postbiotic Lactobacillus reuteri LRE02 Enriched with Sodium Selenite Demonstrates Antidepressant- and Anxiolytic-Like Effects in Mice.Molecular neurobiology · 2026Article
- Mechanism of Buzhong Yiqi decoction for Hashimoto's thyroiditis: insights from gut microbiota and metabolomics.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Role of gut microbiota metabolites in maintaining intestinal health and preventing weaning-associated diarrhea in piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- Research Progress on the Role ofBiology · 2026Review
- Insomnia: the gut microbiome connection, prospects for probiotic and postbiotic therapies, and future directions.Journal of advanced research · 2026Review
- Synergistic Effects of Plant Polysaccharides and Probiotics: A Novel Dietary Approach for Parkinson's Disease Intervention.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Genome-wide association analysis reveals specialization to hosts and niches in multiple species of the Lactobacillaceae.The ISME journal · 2026Article
- Integrating Gut-Brain Axis: Exploring the Neurogastrointestinal Interactions and Therapeutic Potentials in Autism Spectrum Disorder.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Review
191 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H(2) receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.