Gut microbiota as a potential predictor of therapeutic response in adults with Crohn’s disease: A systematic review

Table 1 Characteristics of the studies included in the systematic review

Ref.	Study design patient details	Sample and microbiota assessment technique	Therapy given, definition of response, duration of follow-up
Studies using TNF inhibitors
Chen et al[58], 2022, China	Retrospective study. n = 8. Age > 18 years	Stool sample. 16S rRNA gene sequencing	Adalimumab. Remission: CDAI < 150. 12 weeks
Park et al[64], 2022, Korea	Prospective study. n = 10. Mean age 31 years	Stool and saliva sample. 16S rRNA gene sequencing	Infliximab. Adalimumab. Response: Decrease in CDAI > 70 points or Remission: CDAI < 150 points. 3 months
Sanchis-Artero et al[66], 2021, Spain	Prospective multicenter study. n = 27. Mean age 41.4 ± 17.4 years. Men 55.6%	Stool sample. 16S rRNA gene sequencing	Infliximab. Adalimumab. Response assessment by Clinical, laboratory, stool tests. 3 months and 6 months
Yilmaz et al[68], 2019, Switzerland	Retrospective study. n = 270	Mucosal tissue sample. 16S rRNA gene sequencing	Anti TNF drugs. Response: Clinical and biochemical. Up to 9 years
Aden et al[56], 2019, Germany	Prospective study. n = 18	Stool sample. 16S rRNA gene sequencing	Anti TNF drugs. Response: HBI decrease ≥ 2. Remission: HBI ≤ 4. 2, 6, 14, and 30 weeks
Ding et al[59], 2020, United Kingdom	Prospective study. n = 76. Mean age 38.49 ± 14.6 years. Males 47%	Stool sample. 16S rRNA gene sequencing	Infliximab. Adalimumab. Response: Clinical indices and objective markers including FC, CRP, and radiological or endoscopic improvement. 3 monthly follow-up to 16 months
Guo et al[62], 2024, China	Prospective study. n = 28	Stool sample. 16S rRNA gene and ITS2 gene sequencing	Infliximab. Remission based on symptoms and HBI. 14 weeks
Dovrolis et al[60], 2020, Greece	Prospective study. n = 10	Mucosal tissue sample. 16S rRNA gene sequencing	Infliximab. Complete responder: HBI < 4, normal CRP and mucosal healing. 12-20 weeks
Ribaldone et al[65], 2019, Italy	Prospective study. n = 20. Median age 52.5 (26–69) years. Males: 12 (60%)	Stool sample. 16S rRNA gene sequencing	Adalimumab. Response: Decrease in the HBI score > 2 or HBI 4, 6 months
Ventin-Holmberg et al[67], 2021, Finland	Prospective study. CD-25	Stool sample. 16S rRNA gene and ITS1 gene sequencing	Infliximab. 12 weeks
Zhou et al[10], 2018, China	Prospective study. CD-16	Stool sample. 16S rRNA gene sequencing	Infliximab. Clinical response: ≥ 70-point reduction in CDAI. Clinical remission: CDAI < 150. 30 weeks
Study using integrin inhibitors
Ananthakrishnan et al[57], 2017, United States	Prospective. n = 47	Stool sample. Shotgun metagenome sequencing	Vedolizumab. Response: HBI < 4 or reduction in HBI by ≥ 3 points. 14 weeks
Study using interleukin inhibitor
Doherty et al[9], 2018, United States	Prospective study. n = 232. Mean age 38 ± 13 years. Males 36.6%	Stool sample. 16S rRNA gene sequencing	Ustekinumab. Response: Decrease in CDAI > 100 points or Remission: CDAI < 150 points, 6 weeks
Study using drugs from multiple class
Effenberger et al[61], 2021, Austria and Germany	Prospective study. n = 43	Stool sample. 16S rRNA gene sequencing	Azathioprine. Anti-TNF inhibitors. Remission: CDAI < 150. 12 and 30 weeks
Lee et al[63], 2021, United States	Prospective study. n = 108	Stool sample. Metagenomic sequencing	Anti cytokine (Anti TNF, Ustekinumab). Anti integrin (Vedolizumab). Response: Clinical and endoscopic, 14 weeks and 52 weeks
Caenepeel et al[69], 2024, Belgium	Prospective study. CD-203	Stool sample. 16S rRNA gene sequencing	Infliximab, Adalimumab, Golimumab, Vedolizumab, Ustekinumab. Response: Endoscopic remission SES CD < 3 or absence of ulceration, 24 weeks

TNF: Tumour necrosis factor; CD: Crohn’s disease; CDAI: Crohn’s disease activity index; HBI: Harvey Bradshaw index; FC: Fecal calprotectin; CRP: C-reactive protein; ITS: Internal transcribed spacer; SES: Simple endoscopic score.