# Gut Microbial Composition, Oxidative Stress, and Immunity in Metabolic Disease: Toward Personalized Interventions

**Authors:** Xuangao Wu, Baide Mu, Guanhao Li, Rui Du, Sunmin Park

PMC · DOI: 10.3390/antiox15020175 · Antioxidants · 2026-01-29

## TL;DR

This review explores how gut microbes influence oxidative stress and immunity in metabolic diseases, suggesting personalized interventions based on microbial patterns.

## Contribution

The paper introduces a framework for using gut microbial configurations to guide precision nutrition and therapeutic strategies in metabolic disorders.

## Key findings

- Gut microbial patterns correlate with host redox homeostasis and disease susceptibility in metabolic disorders.
- Bacteroides-enriched communities may promote inflammation, while Prevotella and Bifidobacterium configurations may have anti-inflammatory effects.
- Microbiota-stratified interventions show promise but require further clinical validation.

## Abstract

This review examines how distinct gut microbial community configurations—characterized by differential enrichment of Bacteroides, Prevotella, Ruminococcus, Bifidobacterium, and Lachnospira—may be associated with variations in host redox homeostasis through microbiota-derived metabolites, including short-chain fatty acids, secondary bile acids, and tryptophan derivatives. These compositional patterns represent reproducible features across populations and correlate with differential disease susceptibility in metabolic disorders. While microbial communities exist along compositional continua rather than discrete clusters, stratification based on dominant patterns offers a pragmatic framework for interpreting large-scale microbiome datasets and guiding precision nutrition interventions. Observational evidence suggests Bacteroides-enriched communities may associate with pro-inflammatory signatures, whereas Prevotella- Ruminococcus, Proteobacteria, Bifidobacterium, and Lachnospira-enriched configurations may exhibit anti-inflammatory or antioxidant characteristics in certain populations. However, inter-population variability and species- and strain-level heterogeneity limit generalization. Condition-dependent effects are exemplified by Prevotella copri, which demonstrates pro-inflammatory responses in specific settings despite beneficial profiles in others. When dysbiosis compromises intestinal barrier integrity, microbial translocation may amplify chronic oxidative stress and immune activation. We evaluate therapeutic potential of beneficial genera including Lactobacillus and Bifidobacterium while examining the dose-dependent, context-specific, and sometimes paradoxical effects of key metabolites. Microbiota-stratified therapeutic strategies—personalizing dietary, probiotic, or prebiotic interventions to baseline community composition—show promise but remain at proof-of-concept stage. Current evidence derives predominantly from cross-sectional and preclinical studies; prospective interventional trials linking community stratification with oxidative stress biomarkers remain scarce. The community–redox relationships presented constitute a hypothesis-generating framework supported by mechanistic plausibility and observational associations, rather than established causal pathways. Future research should prioritize intervention studies assessing whether aligning therapeutic approaches with baseline microbial configurations improves outcomes in oxidative stress-related metabolic disorders.

## Linked entities

- **Species:** Bacteroides (taxon 816), Prevotella (taxon 838), Ruminococcus (taxon 1263), Bifidobacterium (taxon 1678), Lachnospira (taxon 28050), Lactobacillus (taxon 1578)

## Full-text entities

- **Genes:** Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Irs1 (insulin receptor substrate 1) [NCBI Gene 16367] {aka G972R, IRS-1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, FFAR2 (free fatty acid receptor 2) [NCBI Gene 2867] {aka FFA2R, GPR43}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}
- **Diseases:** prediabetes (MESH:D011236), Pancreatic beta-Cell Dysfunction (MESH:D010195), cancer (MESH:D009369), diabetes (MESH:D003920), Dysbiosis (MESH:D064806), endothelial dysfunction (MESH:D014652), Mitochondrial dysfunction (MESH:D028361), Parkinson's Disease (MESH:D010300), MASLD (MESH:D008107), Chronic Inflammation (MESH:D007249), injury to (MESH:D014947), metabolic, cardiovascular, and neurodegenerative diseases (MESH:D019636), hyperglycemia (MESH:D006943), metabolic syndrome (MESH:D024821), fibrosis (MESH:D005355), post-traumatic brain injury (MESH:D004834), Metabolic Diseases (MESH:D008659), fat loss (MESH:D004620), colorectal adenoma (MESH:D000236), tumorigenesis (MESH:D063646), Obesity (MESH:D009765), autoimmune (MESH:D001327), Toxicity (MESH:D064420), Insulin Resistance (MESH:D007333), CVD (MESH:D002318), hyperglycemic (MESH:D006944), atherosclerosis (MESH:D050197), gut (MESH:C536735), colorectal cancer (MESH:D015179), metabolic endotoxemia (MESH:D019446), RA (MESH:D001172), ulcerative colitis (MESH:D003093), neuropathology (MESH:D009422), immune dysregulation (OMIM:614878), hepatic diseases (MESH:D056486), liver axis dysfunction (MESH:D017093), constipation (MESH:D003248), type 2 diabetes (MESH:D003924), depression (MESH:D003866), FMT (MESH:D005242), IBD (MESH:D015212)
- **Chemicals:** FOS (MESH:C116580), 3-hydroxypropionaldehyde (MESH:C047158), polysaccharide (MESH:D011134), KYNA (MESH:D007736), lactate (MESH:D019344), MDA (MESH:D015104), TMAO (MESH:C005855), P (MESH:D010758), sugar (MESH:D000073893), IPA (MESH:C000723775), acid (MESH:D000143), oxygen (MESH:D010100), sulfide (MESH:D013440), succinate (MESH:D019802), deoxycholic acid (MESH:D003840), NO (MESH:D009569), 3-HK (MESH:C005045), QUIN (MESH:D017378), BCAAs (MESH:D000597), inulin (MESH:D007444), 4-hydroxynonenal (MESH:C027576), kynurenine (MESH:D007737), indoles (MESH:D007211), AGE (MESH:D017127), luminal (MESH:D010634), lithocholic acid (MESH:D008095), Propionate (MESH:D011422), vedolizumab (MESH:C543529), carbohydrate (MESH:D002241), malondialdehyde (MESH:D008315), fatty acid (MESH:D005227), XOS (MESH:C570991), thiol (MESH:D013438), Butyrate (MESH:D002087), Amino Acid (MESH:D000596), NADPH (MESH:D009249), RNS (MESH:D026361), superoxide (MESH:D013481), Antioxidant Compounds (-), H2O2 (MESH:D006861), Bile Acids (MESH:D001647), H2S (MESH:D006862), Sulfur (MESH:D013455), melatonin (MESH:D008550), indole (MESH:C030374), glucose (MESH:D005947), 5-HT (MESH:D012701), ROS (MESH:D017382), SCFA (MESH:D005232), hexosamine (MESH:D006595), NAD+ (MESH:D009243), Acetate (MESH:D000085), IA (MESH:C030737), I3C (MESH:C012381), guanosine (MESH:D006151), alcohol (MESH:D000438), Tryptophan (MESH:D014364), fumarate (MESH:D005650), lipid (MESH:D008055), cysteine (MESH:D003545)
- **Species:** Lacticaseibacillus rhamnosus GG (strain) [taxon 568703], Lacticaseibacillus rhamnosus (species) [taxon 47715], Lactobacillus (genus) [taxon 1578], Prevotella (genus) [taxon 838], Geobacillus sp. g (species) [taxon 422286], Mediterraneibacter gnavus (species) [taxon 33038], Mus musculus (house mouse, species) [taxon 10090], Escherichia coli (E. coli, species) [taxon 562], Ruminococcaceae [taxon 541000], Bifidobacterium longum (species) [taxon 216816], Faecalibacterium (genus) [taxon 216851], Ruminococcus (genus) [taxon 1263], Agathobacter rectalis (species) [taxon 39491], Roseburia (genus) [taxon 841], Bacteroides uniformis (species) [taxon 820], Ruminococcus bromii (species) [taxon 40518], Parabacteroides distasonis (species) [taxon 823], Pseudomonadota (proteobacteria, phylum) [taxon 1224], Desulfovibrio (genus) [taxon 872], Faecalibacterium prausnitzii (species) [taxon 853], Homo sapiens (human, species) [taxon 9606], Bifidobacterium (genus) [taxon 1678], Alistipes (genus) [taxon 239759], Lactobacillus johnsonii (species) [taxon 33959], Segatella copri (species) [taxon 165179], Bacteroides (genus) [taxon 816], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Lacticaseibacillus casei (species) [taxon 1582], Bilophila (genus) [taxon 35832], Akkermansia muciniphila (species) [taxon 239935], Lachnospira (genus) [taxon 28050], Limosilactobacillus reuteri (species) [taxon 1598], gut metagenome (species) [taxon 749906], Lactiplantibacillus plantarum (species) [taxon 1590], Odoribacter splanchnicus (species) [taxon 28118], Bifidobacterium bifidum (species) [taxon 1681], Levilactobacillus brevis (species) [taxon 1580], Enterobacteriaceae (enterobacteria, family) [taxon 543]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938183/full.md

## References

196 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938183/full.md

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Source: https://tomesphere.com/paper/PMC12938183