Evidence map›Paper›PMID 41668172›Full record

SynthesisJournal of translational medicine2026

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.

Do-Young Kim, Jaeyoung Youn, Naeun Kang, Sung-Il Cho, In-Hyuk Ha

Abstract readSystematic ReviewCase Reports
In one paragraph

Synthesis in Journal of translational medicine, 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

5 authors.

Do-Young KimDepartment of Acupuncture & Moxibustion, Jaseng Korean Medicine Hospital, Seoul, 06110, Republic of Korea.
Jaeyoung YounDepartment of Acupuncture & Moxibustion, Jaseng Korean Medicine Hospital, Seoul, 06110, Republic of Korea.
Naeun KangDepartment of Public Health Science, Seoul National University, Seoul, 08826, Republic of Korea.
Sung-Il ChoDepartment of Public Health Science, Seoul National University, Seoul, 08826, Republic of Korea.
In-Hyuk HaJaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 540, Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea. hanihata@gmail.com.ORCID 0000-0002-5020-6723

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined.

methodsWe report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12 weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted.

resultsThe patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n = 8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy.

conclusionBrain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.

Indexed as

BrainBrain-Gut AxisCOVID-19Fatigue Syndrome, ChronicAdultElectroacupunctureFemaleHumansMaleMiddle AgedPost-Acute COVID-19 SyndromeSARS-CoV-2Brain–gut axisChronic fatigue syndromeElectroacupunctureFlu-like symptomLong COVIDME/CFSNeuroinflammationPost-exertional malaiseRandomized controlled trialVagus nerve

Identifiers

PMID41668172
PMCPMC12990451

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.