Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools
Abstract
1. Introduction
2. Changes in Gut Microbiota Are Associated with IBD
3. The Old Paradigm of Gut Microbiota Modulation in IBD
3.1. Antibiotics
3.2. Probiotics
3.3. Prebiotics
3.4. Postbiotics
3.5. Symbiotics
4. Revolutionizing Microbiota Therapeutics in IBD: The New Paradigm
4.1. Fecal Microbiota Transplantation
4.2. Rising Star Probiotics: Faecalibacterium Prausnitzii
4.3. Rising Star Probiotics: Akkermansia Muciniphila
4.4. Bacterial Consortia
4.5. Bacteriophages
4.6. Engineered Probiotics
4.7. Direct Metabolic Pathways Modulation and Nanotherapeutics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Probiotic Tested | Reference | Disease Activity (UC vs. CD) | Trial Design | Outcomes |
---|---|---|---|---|
L. rhamnosus NCIMB 30174, L. plantarum NCIMB 30173, L. acidophilus NCIMB 30175 and E. faecium NCIMB 30176 | Bjarnason et al., 2019 [90] | Quiescent UC and CD | Single center, randomized, double-blind, placebo-controlled trial | No significant differences in IBD-QoL scores; reduced intestinal inflammation in UC patients |
E. coli Nissle 1917 | Park et al., 2022 [91] | Mild to moderate active UC | Multicenter, double-blind, randomized, placebo-controlled study | Prevents exacerbations of IBD-QoL scores; achieves clinical response and endoscopic remission |
L. paracasei (A234), L. gasseri (A237), L. rhamnosus (A119), L. acidophilus (A118), L. plantarum (A138), L. casei (A179), L. reuteri (A113), L. lactis (A328), B. animalis subsp lactis (A026), B. breve (A055), B. longum subsp. longum (A027), B. bifidum (A058), B. longum subsp. infantis (A041) species. | Agraib et al., 2022 [92] | Mild to moderate UC | Randomized, double-blind, placebo-controlled, parallel-arms, multicenter study | Induces clinical (partial Mayo score) and biochemical remission in UC patients |
E. coli Nissle 1917 | Oh et al., 2021 [93] | Quiescent UC | Uncontrolled, observational, retrospective study | Additional administration of E. coli Nissle 1917 may improve UC symptoms |
Kefir (L. pentosus, L. brevis, L. plantarum, L. fermentum, L. kefiri, and L. lindneri) | Yilmaz et al., 2019 [94] | Active UC and CD | single-center, prospective, open-label randomized controlled trial | Kefir consumption may modulate gut microbiota and enhance short-term quality of life |
B. breve strain Yakult, L. Acidophilus | Matsuoka et al., 2018 [95] | Quiescent UC | Multicenter, randomized, placebo-controlled, double-blind parallel-group study | No effect on relapse timing |
S. faecalis T-110, C. butyricum TO-A, B. mesentericus TO-A | Yoshimatsu et al., 2015 [96] | Quiescent UC | Randomized, double-blind, placebo-controlled study | Supports clinical remission mantainance |
L. reuteri ATCC55730 | Oliva et al., 2012 [97] | Mild to moderate active distal UC (children) | Prospective randomized, placebo-controlled study | Reduces Mayo score and histological scores; modulates mucosal cytokine expression |
S. thermophilus BT01, B. breve BB02, B. longum * BL03, B. infantis * BI04, L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, L. delbrueckii subs | Tursi et al., 2010 [98] | Relapsing mild-moderate UC | Multicenter, double-blind, randomized placebo-controlled, parallel study | Decreases UCDAI scores; improves rectal bleeding; may reinduce remission after 8 weeks of treatment |
L. acidophilus, L. plantarum, L. casei, L. delbruecki subspecies bulgaricus, B. breve, B. longum, B. infantis, S. salivarius subspecies thermophilus | Miele et al., 2009 [99] | Active UC (children) | Randomized, placebo-controlled, double-blind study | Maintains clinical and endoscopic remission |
Lactobacillus GG | Zocco et al., 2006 [100] | Quiescent UC | Single center, prospective, open-label randomized trial | Maintains remission compared to mesalazine; delays UC relapse |
B. breve strain Yakult, B. bifidum strain Yakult, L. acidophillus strain | Kato et al., 2004 [101] | Mild to moderate active UC | randomized placebo-controlled clinical trial | Reduces clinical activity index; significantly improves post-treatment endoscopic activity index and histological score |
Way of Administration | Reference | Disease Activity | Trial Design | Results Summary |
---|---|---|---|---|
FMT by colonoscopy | Deleu et al., 2024 [127] | Moderate to severe UC | Multi-centric, double-blind, sham-controlled randomized trial | Failure to achieve steroid-free clinical remission at week 8 |
Lyophilized oral FMT | Haifer. et al., 2022 [128] | Mild to moderate UC | Double-blind, randomized, placebo-controlled trial | Induction of clinical remission with endoscopic remission or response at week 8; maintenance of clinical, endoscopic, and histological remission at week 56 |
FMT by colonoscopy and enemas | Shabat et al., 2022 [129] | Moderate to severe active UC | Single, blinded, randomized, controlled trial | UC exclusion diet (UCED) leads to higher clinical remission and mucosal healing than single donor FMT, with or without diet |
Encapsuled oral FMT | Crothers et al., 2021 [130] | Mild to moderate UC | single center, double-blinded, placebo-controlled, randomized control trial | Prolonged durability of FMT-induced changes in gut bacterial community structure; association between MAIT cell cytokine production and clinical response |
FMT by colonoscopy and enemas | Costello et al., 2019 [131] | Mild to moderate UC | Double blind, randomized, clinical trial | A 1-week treatment with anaerobically prepared donor FMT results in higher remission rates at week 8 compared to autologous FMT |
FMT by colonoscopy and enemas | Paramsothy et al., 2017 [132] | Mild to moderate UC | Multicenter, double-blind, randomized, placebo-controlled trial | Induction of clinical remission and endoscopic improvement |
FMT via enema | Moayyedi et al., 2015 [133] | Mild to severe UC | Double-blind randomized controlled trial | Induction of remission in a significantly higher percentage of patients with active UC; greater microbial diversity |
FMT via nasoduodenal tube | Rossen et al., 2015 [134] | Mild to moderate UC | Single-center, double-blind, placebo-controlled, randomized, proof-of-concept phase 2 trial | No significant difference in clinical and endoscopic remission between patients receiving FMT from healthy donors and those receiving autologous FMT |
Bacterial Consortia | Reference | Trial Design | Results Summary |
---|---|---|---|
BAC (bile acid consortium, made up of Clostridium AP sp000509125, Bacteroides ovatus, and Eubacterium limosum) | Zhou et al., 2023 [187] | DSS-induced colitis mice model | Increases secondary bile acids (Ursodeoxycholic acid (UDCA) and Lithocholic acid (LCA)) in vitro; exerts protective effects against colitis (reduces weight loss, increases colon length, strengthens the intestinal barrier) |
Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus acidophilus (Lactobacillus spp.), and Bifidobacterium lactis (Bifidobacterium spp.) | Xu et al., 2022 [188] | DSS-induced colitis mice model | Alleviates disease phenotype; restores the composition and structure of the gut microbiota |
GUT 103 (strains of genera Bacteroides, Akkermansia, Clostridium, Faecalibacterium) and GUT108 (strains of Clostridium, Intestinimonas, Bitterella, Barneseilla) | Van der Leile et al., 2021 [189] | Immune-mediated colitis in germ free mice | GUT-103 and GUT-108: Correct the dysbiotic microbiome environment; activate IL-10-producing immune cells; reduce inflammatory responses; restore bacterial metabolic profiles to levels observed in healthy individuals’ stool samples |
BMC332 | Polonsky et al., 2021 [190] | DSS-induced colitis in mice | Exhibits anti-inflammatory properties; maintains intestinal barrier integrity |
Engineered Probiotic | Reference | Trial Design | Results Summary |
---|---|---|---|
E. coli | Wang et al., 2021 [216] | DSS-induced colitis in mice |
|
E. coli | Cui et al., 2021 [217] | DSS-treated colitis in mice |
|
L. paracasei (KBL382,384,385) | Kim et al., 2019 [220] | DSS-induced colitis in mice |
|
B. longum | Liu et al., 2016 [222] | DSS-induced colitis in mice |
|
B. longum | Wei et al., 2016 [223] | DSS-induced colitis in mice |
|
OMV of Bacteroides thetaiotaomicron (Bt) | Carvalho et al., 2019 [225] | DSS-induced colitis in mice |
|
OMV from E. coli Nissle 1917 | Fabrega et al., 2017 [226] | DSS-induced colitis in mice |
|
E. coli | Zhang et al., 2018 [227] | DSS-induced experimental colitis in mice |
|
L. lactis | Hanson et al., 2014 [228] | DSS-induced colitis in mice |
|
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Murgiano, M.; Bartocci, B.; Puca, P.; di Vincenzo, F.; Del Gaudio, A.; Papa, A.; Cammarota, G.; Gasbarrini, A.; Scaldaferri, F.; Lopetuso, L.R. Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools. Int. J. Mol. Sci. 2025, 26, 3059. https://doi.org/10.3390/ijms26073059
Murgiano M, Bartocci B, Puca P, di Vincenzo F, Del Gaudio A, Papa A, Cammarota G, Gasbarrini A, Scaldaferri F, Lopetuso LR. Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools. International Journal of Molecular Sciences. 2025; 26(7):3059. https://doi.org/10.3390/ijms26073059
Chicago/Turabian StyleMurgiano, Marco, Bianca Bartocci, Pierluigi Puca, Federica di Vincenzo, Angelo Del Gaudio, Alfredo Papa, Giovanni Cammarota, Antonio Gasbarrini, Franco Scaldaferri, and Loris Riccardo Lopetuso. 2025. "Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools" International Journal of Molecular Sciences 26, no. 7: 3059. https://doi.org/10.3390/ijms26073059
APA StyleMurgiano, M., Bartocci, B., Puca, P., di Vincenzo, F., Del Gaudio, A., Papa, A., Cammarota, G., Gasbarrini, A., Scaldaferri, F., & Lopetuso, L. R. (2025). Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools. International Journal of Molecular Sciences, 26(7), 3059. https://doi.org/10.3390/ijms26073059