Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood
Abstract
:1. Introduction
2. Differences and Similarities in Microbial Modulation of Pediatric Versus Adult Patients with IBD
2.1. Nutritional Therapies
2.1.1. Exclusive Enteral Nutrition (EEN)
2.1.2. Prebiotics and Dietary Fibre
2.2. Probiotics
2.3. Antibiotics
2.4. Fecal Microbiota Transplantation (FMT)
Study | Type | n | Age | Severity | Route | Donor | Type of FMT | Clinical Response | Change in Microbiome | Follow Up |
---|---|---|---|---|---|---|---|---|---|---|
Sokol 2020 [111] | CD- Colonic and ileocolonic | 8 | 18–70 | Originally HBI > 4, but post remission induction with steroids | Colonoscopy Single dose | Healthy donors age 20–50 | Fresh | 25% difference between FMT to control (NS) | -No significant changes in donor microbiota between those who responded and those who did not -Outcome of >60% colonization of the donor microbiota at 6 weeks was not achieved | 24 weeks |
Paramsothy 2017 [112] (FOCUS study) Paramsothy 2019 [116] (microbial analysis of FOCUS study) | UC | 41 | 18–75 | Mayo score 4–10 IBDQ score 123 (99–157) | Initial colonoscopic and then intensive multidonor FMT enemas 5 d/wk for 8 weeks | Blended homogenized stool from 3–7 unrelated donors | Fresh | Primary endpoint of steroid-free clinical remission together with endoscopic remission or response at week 8. 27% (11 of 41) of patients assigned fecal microbiota transplantation met the primary endpoint, compared with 8% (three of 40) of those allocated placebo (p = 0.021) | Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans and increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis | 24 weeks |
Costello 2019 [117] | UC | 38 | ≥18 | total Mayo score of 3 to 10 points and an endoscopic subscore of ≥2 | Colonoscopy followed by 2 enemas over 7 days | Anaerobically prepared pooled donor FMT or autologous FMT | Frozen | OR of steroid free remission of 5 (1.2–20.1) p = 0.03. Endoscopic remission was NS | Increased abundance of Anaerofilum pentosovorans and Bacteroides coprophilus species was strongly associated with disease improvement following donor FMT Changes in SCFA were not significant | 8 weeks and 12 months (but by 12 months most of the patients had donor FMT) |
Yang 2020 [114] | CD | 27 | 18–60 | Mild to moderate CDAI > 150 | Randomized to colonoscopy vs. Gastroscopy A second FMT 1 week afterwards | Healthy donors | Fresh | No significant differences were seen between the gastroscopy and colonoscopy groups (clinical response, 76.9% and 78.6%, respectively; clinical remission, 69.2% and 64.3%, respectively | Only investigated changes between patients and donors not between study groups | 8 weeks |
Schierova 2020 [118] | Left sided UC | 8 | Median 40 IQR (31–66) | Median mayo score of 5.5 | 5 enemas administered at the first week, then once a week until the end of 6th week | 1 healthy donor | Frozen | Clinical response was 62.5% in both FMT and 5-ASA groups | Faecalibacterium, Blauti, Coriobacteria, Collinsela, Slackia, and Bifidobacterium were significantly more frequent in patients who reached clinical remission | 12 weeks |
Sood 2019 [119] | UC | 31 | Mean age 33 SD ± 12.4 | Clinical remission | Colonoscopy every 8 weeks for 48 weeks | 1 healthy donor | Frozen | NS in clinical remission Endoscopic remission in 58.1% of FMT and 26.7% in placebo p = 0.026 | No microbiome analysis | 48 weeks |
Crothers 2021 [115] | UC | 6 | ≥18 | Mayo score between 4 and 10 | Colonoscopy and then 12 weeks of daily Encapsulated oral FMT | 2 healthy donors | Frozen | NS | FMT lead to community-level changes in the gut microbiota creating measurable similarity (beta diversity, Jensen-Shannon divergence index) between FMT subjects and their donor. p < 0.01 | 36 weeks |
2.5. Postbiotics
3. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study | Type | n | Age | Severity | Antibiotics | Clinical Response | Type of Analysis | Change in Microbiome | Follow Up |
---|---|---|---|---|---|---|---|---|---|
Turner 2020 [100] | UC | 16 | 18-Feb | PUCAI ≥ 65 | Vancomycin, Doxycycline, Amoxicillin, Metronidazole | Lower PUCAI levels at antibiotic group | 16S RNA in stool | Diversity was reduced. Some patients had higher Escherichia levels after treatment. | 12 months |
Recovery after 2 months | |||||||||
Sporckett 2019 [99] | CD | 67 | 18-May | 10 ≤ PCDAI ≤ 40 | Metronidazole Versus Metronidazole+ Azithromycin | NS | 16S rRNA in stool | Both groups had decreased diversity. Pre-antibiotic microbiome was able to predict response to Metronidazole | 12 weeks |
Fcal reduction in combination group | |||||||||
Levine 2018 [101] | (73 in clinical response analysis) | ||||||||
Koido 2014 [102] | UC | 105 were treated, 12 stool samples analyzed | ≥18 | Mild to severe UC, with at least 1 relapse a year | Amoxicillin, Tetracycline and Metronidazole | NS | 16S | NS | Treatment 2 weeks, follow up for 3 months |
rDNA | |||||||||
Real-time PCR quantification of F.Varium DNA | |||||||||
in tissue | |||||||||
Maccaferri 2010 [96] | CD | 4 | N/A | CDAI > 200 | Rifaximin | Not reported | Fecal samples were implemented in colonic models and then analyzed by FISH, qPCR and H-NMR spectroscopy | Increase in concentration of Bifidobacterium, Atopobium and Faecalibacterium prausnitzii. | 12 weeks |
Increases in SCFA, propanol, decanol, nonanone and aromatic organic compounds, and decreases in ethanol, methanol and glutamate. |
Crohn’s Disease | Ulcerative Colitis | ||||
---|---|---|---|---|---|
Intervention | Children | Adults | Children | Adults | |
EEN | Microbiome effect | ↓ Bacteroides ↓ Clostridium Coccoides ↓ Diversity Butyrate ↓ | ↓ Enterobacteriaceae ↓ Diversity | N\D | N\D |
Clinical response | √ | X | X | X | |
Prebiotics | Microbiome effect | ↑ Bifidobacterium | N\D | ↑ Bifidobacterium | Bacteroidetes ↑ Butyrate ↑ |
Clinical response | √ Protecting factor | √ Protecting factor | N\D | √ | |
Probiotics | Microbiome effect | N\D | N\D | N\D | N\D |
Clinical response | X | X | √ | √ | |
Antibiotics | Microbiome effect | ↓ Diversity | Bifidobacterium (?) ↑ SCFA (?) ↑ | Escherichia ↑ ↓ Diversity | No change |
Clinical response | X | X | √ (√√ VEOIBD) | X | |
FMT | Microbiome effect | N\D | Variable study results | N\D | Variable study results |
Clinical response | N\D | X | N\D | X | |
Postbiotics | Clinical response | N\D | √ (?) | N\D | √ (?) |
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Eindor-Abarbanel, A.; Healey, G.R.; Jacobson, K. Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood. Int. J. Mol. Sci. 2021, 22, 12506. https://doi.org/10.3390/ijms222212506
Eindor-Abarbanel A, Healey GR, Jacobson K. Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood. International Journal of Molecular Sciences. 2021; 22(22):12506. https://doi.org/10.3390/ijms222212506
Chicago/Turabian StyleEindor-Abarbanel, Adi, Genelle R. Healey, and Kevan Jacobson. 2021. "Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood" International Journal of Molecular Sciences 22, no. 22: 12506. https://doi.org/10.3390/ijms222212506