# The Role of the Gut Microbiome in Clinical Outcomes of Colorectal Cancer: A Systematic Review (2020–2025)

**Authors:** Iara Santos, Joana Liberal, Paulo Teixeira, Diana Martins, Fernando Mendes

PMC · DOI: 10.32604/or.2025.070281 · Oncology Research · 2026-02-24

## TL;DR

This review explores how gut microbes affect colorectal cancer treatment outcomes and highlights the need for more research to understand these relationships.

## Contribution

The study systematically reviews recent evidence on gut microbiome variations and their influence on CRC treatment responses.

## Key findings

- Therapies increased probiotic taxa and reduced pro-carcinogenic bacteria.
- No consistent pattern of improved clinical outcomes was observed.
- Individual characteristics and treatment mechanisms influence microbiome modulation.

## Abstract

The Colorectal Cancer (CRC) pathogenesis and therapeutic efficacy are influenced by the gut microbiome, making it a promising biomarker for predicting treatment responses and adverse effects. This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes.

Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025, respectively. Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes. RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies, respectively. Data extracted was narratively analyzed.

Six studies involving a total of 361 individuals were included. Therapeutic interventions, either standard treatments and/or those targeting the gut microbiome, generally increased probiotic taxa and reduced pro-carcinogenic bacteria. However, no consistent pattern of improved clinical outcomes was observed, suggesting that treatment mechanisms, the tumor’s nature, and individual characteristics play critical roles in microbiome modulation.

The gut microbiome holds significant potential in clinical settings. Nonetheless, further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms, the tumor’s nature, and individual characteristics as modulators, in order to optimize clinical outcomes.

## Linked entities

- **Diseases:** Colorectal Cancer (MONDO:0005575)

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, HP (haptoglobin) [NCBI Gene 3240] {aka HP2ALPHA2, HPA1S}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, MBP (myelin basic protein) [NCBI Gene 4155], ARG1 (arginase 1) [NCBI Gene 383], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, RBBP4 (RB binding protein 4, chromatin remodeling factor) [NCBI Gene 5928] {aka NURF55, RBAP48, lin-53}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}, ODC1 (ornithine decarboxylase 1) [NCBI Gene 4953] {aka BABS, NEDBA, NEDBIA, ODC}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}
- **Diseases:** Natural Killer T (MESH:D000077428), metabolic (MESH:D008659), carcinogenesis (MESH:D063646), vitamin D deficiency (MESH:D014808), Osmotic diarrhea (MESH:D003967), adenoma (MESH:D000236), CMS (MESH:C535673), fatigue (MESH:D005221), III-IV disease (MESH:D020432), Obesity (MESH:D009765), hypoxic (MESH:D002534), CMV (MESH:D003586), rectal cancer (MESH:D012004), abdominal pain (MESH:D015746), Microsatellite Instability (MESH:D053842), adenoma-carcinoma (MESH:D000230), Stable disease (MESH:D060050), CMS1 tumors (MESH:D009369), hand-foot syndrome (MESH:D060831), Dysbiosis (MESH:D064806), carcinogenic bacteria (MESH:C000719206), EBV-infected (MESH:D020031), inflammation (MESH:D007249), gastrointestinal symptoms (MESH:D012817), disease (MESH:D004194), CIN (MESH:D043171), MSI-H (MESH:D000848), bloating (MESH:C535647), postoperative ileus (MESH:D045823), constipation (MESH:D003248), peripheral sensory neuropathy (MESH:D010523), MPE (MESH:D005598), CIMP (MESH:D007516), abdominal distention (MESH:D000007), oral mucositis (MESH:D013280), AE (MESH:D064420), colitis (MESH:D003092), gastrointestinal complications (MESH:D005767), bone marrow toxicity (MESH:D001855), Infection (MESH:D007239), viral infections (MESH:D014777), CRC (MESH:D015179), death (MESH:D003643), carcinogenic (MESH:D011230), tumorigenic (MESH:D002471), metastases (MESH:D009362)
- **Chemicals:** thiamine diphosphate (MESH:D013835), pyrimidine (MESH:C030986), Bevacizumab (MESH:D000068258), Oxaliplatin (MESH:D000077150), acetic (MESH:D019342), spermine (MESH:D013096), propionic acid (MESH:C029658), acetyl-CoA (MESH:D000105), N1-AcSPD (MESH:C017988), 5-FU (MESH:D005472), Metronidazole (MESH:D008795), colibactin (MESH:C569566), L-histidine (MESH:D006639), macrogol (MESH:D011092), glycan (MESH:D011134), N1, N8-diacetylspermidine (MESH:C093909), formate (MESH:C030544), Vitamin D (MESH:D014807), sodium chloride (MESH:D012965), N1-AcSP (MESH:C029452), paraffin (MESH:D010232), L-methionine (MESH:D008715), ROS (MESH:D017382), folate (MESH:D005492), L-threonine (MESH:D013912), SCFA (MESH:D005232), 5-HT (MESH:D012701), Formalin (MESH:D005557), alcohol (MESH:D000438), spermidine (MESH:D013095), acetate (MESH:D000085), L-lysine (MESH:D008239), Cefazolin (MESH:D002437), lipid (MESH:D008055), LPS (MESH:D008070), butyric acid (MESH:D020148), Polyamine (MESH:D011073), XELOX (MESH:C519688), L-arginine (MESH:D001120), carbohydrate (MESH:D002241), propionate (MESH:D011422), putrescine (MESH:D011700), amino acid (MESH:D000596), butyrate (MESH:D002087), Capecitabine (MESH:D000069287), glycerol (MESH:D005990), 1,3-propanediol (MESH:C041787), 25-hydroxyvitamin D (MESH:C104450), oligosaccharides (MESH:D009844), L-ornithine (MESH:D009952), 25(OH)D (-)
- **Species:** Holdemanella biformis (species) [taxon 1735], Nicotiana tabacum (American tobacco, species) [taxon 4097], Lactobacillus acidophilus (species) [taxon 1579], Phocaeicola coprocola (species) [taxon 310298], Sutterella (genus) [taxon 40544], Klebsiella (genus) [taxon 570], Bacteroides gallinarum (species) [taxon 376806], Roseburia (genus) [taxon 841], Hominimerdicola alba (species) [taxon 1264], Ruminococcus bromii (species) [taxon 40518], Ruminococcus sp. YE78 (species) [taxon 1352374], Phascolarctobacterium (genus) [taxon 33024], Enterococcus faecalis (species) [taxon 1351], Veillonella (genus) [taxon 29465], Bacteroides clarus (species) [taxon 626929], Leuconostoc pseudomesenteroides (species) [taxon 33968], Actinomyces (genus) [taxon 1654], Shigella boydii (species) [taxon 621], Eubacterium coprostanoligenes (species) [taxon 290054], Human papillomavirus (species) [taxon 10566], Mus musculus (house mouse, species) [taxon 10090], Mediterraneibacter gnavus (species) [taxon 33038], Anaerobutyricum hallii (species) [taxon 39488], Dialister (genus) [taxon 39948], Bacillus cereus (species) [taxon 1396], Escherichia coli (E. coli, species) [taxon 562], Megamonas (genus) [taxon 158846], Christensenella timonensis (species) [taxon 1816678], Faecalibacterium (genus) [taxon 216851], Blautia (genus) [taxon 572511], Parabacteroides (genus) [taxon 375288], Bacillus infantis (species) [taxon 324767], gut metagenome (species) [taxon 749906], Cytomegalovirus (genus) [taxon 10358], Phocaeicola vulgatus (species) [taxon 821], Klebsiella ornithinolytica (species) [taxon 54291], Fusobacterium nucleatum (species) [taxon 851], Bifidobacterium bifidum (species) [taxon 1681], Faecalibacterium prausnitzii (species) [taxon 853], Homo sapiens (human, species) [taxon 9606], Clostridium (genus) [taxon 1485], Collinsella (genus) [taxon 102106], Segatella copri (species) [taxon 165179], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Bacteroides fragilis (species) [taxon 817], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Rattus norvegicus (brown rat, species) [taxon 10116], Selenomonas (genus) [taxon 970], [Eubacterium] brachy (species) [taxon 35517], Porphyromonas (genus) [taxon 836], Streptococcus (genus) [taxon 1301], Akkermansia muciniphila (species) [taxon 239935]
- **Mutations:** V600E

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12963652/full.md

## References

219 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963652/full.md

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Source: https://tomesphere.com/paper/PMC12963652