Evidence map›Paper›PMID 42851568›Full record

SynthesisFrontiers in immunology2026

The microbiome-nitric oxide axis in cancer immunotherapy: a targeted qualitative systematic review of mechanistic and translational evidence.

Michael Enwere, Nathan S Bryan, Adamu Onu, Mercy Neufeld, Mohamed Toufic El-Hussein, Ibrahim Yakub, Charles Omale, Ogonna Onyedike, Terkaa Atim, Olukayode Agbeyomi and 3 more

Abstract readSystematic Review
In one paragraph

Synthesis in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

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

13 authors.

Michael EnwereGlobal Health Equity Foundation (GHEF), Bear, DE, United States.
Nathan S BryanBryan Therapeutics Inc., Austin, TX, United States.
Adamu OnuInstitute of Medical Sciences Africa, Abuja, Nigeria.
Mercy NeufeldSwedish Medical Center Colorado, Englewood, CO, United States.
Mohamed Toufic El-HusseinAgeCare Research Chair in Older Adults Health, School of Nursing and Midwifery, Faculty of Health, Community and Education, Mount Royal University, Calgary, AB, Canada.
Ibrahim YakubWell-Life Hospital, Abuja, Nigeria.
Charles OmaleRoyal Eye Hospital & Medical Centre, Abuja, Nigeria.
Ogonna OnyedikeFriendly Hospital, Enugu, Nigeria.
Terkaa AtimDepartment of Surgery, Faculty of Clinical Sciences, College of Health Sciences, University of Abuja, Abuja, Nigeria.
Olukayode AgbeyomiDepartment of Public Health, Babcock University, Ilishan-Remo, Ogun State, Nigeria.
Emmanuel DaviesPrimeLife360 Wellness, London, United Kingdom.
Ujuaku E OkekePublic Health Informatics & Data Exchange, Texas Department of State Health Services, Austin, TX, United States.
Laurens HolmesGlobal Health Equity Foundation (GHEF), Bear, DE, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but responses vary substantially among patients. Clinical studies have associated features of the gut microbiome with ICI outcomes, while experimental evidence suggests that microbial metabolites and nitric oxide (NO)-related pathways may influence antitumor immunity and tumor vascular biology. This qualitative systematic review evaluated the evidence supporting a proposed microbiome-NO-ICI framework. Methods: Five databases were searched for peer-reviewed studies published between January 2000 and August 2025. Fifty-four distinct primary studies met the eligibility criteria, comprising 21 clinical studies, 19 animal studies and 14 Results: Several clinical cohorts associated enrichment of Conclusion: The microbiome-NO-ICI axis should be regarded as a testable integrative model linking microbial ecology, immune regulation and tumor vascular biology. Current evidence supports biological plausibility but is insufficient to establish NO- or microbiome-directed interventions as effective adjuncts to ICI therapy. Prospective mechanistic studies and biomarker-driven clinical trials are required before therapeutic translation.

Indexed as

Gastrointestinal MicrobiomeImmune Checkpoint InhibitorsImmunotherapyNeoplasmsNitric OxideAnimalsFecal Microbiota TransplantationHumansTranslational Research, BiomedicalImmune Checkpoint InhibitorsNitric OxideAkkermansia muciniphilacancer immunotherapygut microbiomeimmune checkpoint inhibitors (ICI)microbiome–immune crosstalknitric oxide (NO)short-chain fatty acids (SCFAs)tumor microenvironment (TME)

Identifiers

PMID42851568
PMCPMC13646043

What OpenQuestion holds

Textmetadata
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.