Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

Table 1 Possible microbial pathogens associated with inflammatory bowel disease

Mycobacterium avium subspecies paratuberculosis[19,126,127]

Adherent-invasive Escherichia coli[18,44,45,128]

Clostridium difficile[107,129,130]

Candida albicans[21,49]

Helicobacter sp.[131-133]

Campylobacter sp., such as Campylobacter jejuni and Campylobacter concisus[134-136]

Salmonella sp.[135]

Klebsiella sp.[137]

Yersinia sp.[138]

Listeria sp.[139]

Fusobacterium sp.[140]

Methanosphaera stadtmanae[141]

Bacteroides fragilis[142]

Norovirus[143]

Table 2 Main case series and reports of fecal microbiota transplantation in inflammatory bowel disease treatment

Ref.	IBD type (n)	Stoolmaterial	Volumeinfusion	Infusion route	Frequency	Donor relationship	Characteristics of outcomes
Bennet et al[34], 1989	UC (1)	NR	NR	Enema	1	NR	Documents remission for 6 mo and cease medications
Borody et al[144], 1989	UC (1)	NR	NR	Enema	NR	NR	Documented remission for 3 mo and cease medications.
Borody et al[35], 2003	UC (6)	Fresh	200-300 g/200-300 mL	Enema	6	Related or unrelated	Documented remission from 1 to 13 yr and cease medications
Hamilton et al[112], 2012	UC combinedwith CDI (4)	Fresh orfrozen	220-240 mL	Colonoscopy	1	Related or unrelated	Colitis activity was improved, and CDI was cured
Zainah et al[145], 2012	UC combined with CDI (1)	Fresh	300 mL	Colonoscopy	1	Related	Documented symptom-free for 8 mo without CDI recurrence
Borody et al[146], 2012	UC (3)	Fresh	NR	Repeated rectal infusions	Daily infusion for 2 to 6.5 mo	Related or unrelated	Documented improvement from 1 to 36 mo
Patel et al[147], 2013	UC combined with CDI (3)	Fresh	18-397 g/180-600 mL	Colonoscopy	1	Related or unrelated	Symptoms such as diarrhea improved or resolved 3 mo after FMT
Angelberger et al[105], 2013	UC (5)	Fresh	17-25 g/250 mL +6-12 g/100 mL	Nasojejunal tube + enema	3	Unrelated	None of cases achieved remission, but only one case was response to FMT by week 12; two cases deteriorated 4 wk after FMT
Kump et al[148], 2013	UC (6)	Fresh	300-500 mL	Colonoscopy	1	Unrelated	Documented improvement, but no remission within 2 wk after FMT
De Leon et al[110], 2013	UC combined with CDI (1)	Fresh	600 mL	Colonoscopy	1	Related	UC relapse 9 d after FMT
Kunde et al[108], 2013	UC (10)	Fresh	165 ml	Enema	5	Related	78% and 67% subjects achieved clinical response within 1 wk and 1 mo after FMT, respectively
Borody et al[144], 1989	CD (1)	NR	NR	Enema	NR	NR	Symptoms-free and receiving no medications 4 mo after FMT
Grehan et al[118], 2010	CD (1)	Fresh	200-400 mL	Colonoscopy + enema	1 + 9	NR	CD related improvement was not reported
Hamilton et al[112], 2012	CD combined with CDI (6)	Fresh orfrozen	220-240 mL	Colonoscopy	1 or 2	Related or unrelated	Two cases accepted the second FMT due to CDI recurrence, but the efficacy of FMT on CD was not reported
Patel et al[147], 2013	CD combined with CDI (2)	Fresh	18-397 g/180-600 mL	ColonoscopyUpper endoscopy	2	Related or unrelated	CDI recurred in 1 case after the first FMT by colonoscopy, and a second FMT was performed by upper endoscopy; but the efficacy of FMT on CD was not reported
Gordon et al[109], 2013	CD (1)	Fresh	NR	NR	NR	Related	Response to FMT for 6 mo and then relapsed
Quera et al[149], 2013	CD combined with CDI (1)	NR	NR	Colonscopy	NR	NR	Transient bacteremia occurred 24 h after FMTDocumented symptom-free 5 mo after FMT and CDI disappeared
Zhang et al[36], 2013	CD (1)	Fresh	150 mL	Gastroscope	1	Related	Documented clinical remission for more than 9 mo

FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; CDI: Clostridium difficile infection; CD: Crohn’ disease; NR: Not reported.

Table 3 Donor selection for fecal microbiota transplantation

Absolute exclusion criteria[32,104,124]

Failed to provide informed consent

Systematic and local microbial infections (e.g., pathogenic bacteria, virus, ova and parasites)

Current communicable diseases

Malignancy and chemotherapeutics administration

Chronic gastrointestinal disorders

Peptic ulcer diseases

Gastroesophageal reflux disease

GI polyposis

Inflammatory bowel disease

Irritable bowel syndrome

Chronic constipation

Traveler’s diarrhea

Current GI symptoms

Antibiotics administration

Immunosuppressive agents and biological agents

Other medications impact on the gut microbiota (e.g., proton pump inhibitor, prokinetic agents, steroids, aspirin, probiotics, etc.)

High-risk lifestyles (e.g., intravenous drug abuse, risk sexual behaviors, etc.)

Relative exclusion criteria[32,104,124]

Age < 18 and > 70 yr

History of major GI surgery

Metabolic syndrome

Diabetes mellitus

Abnormal body mass index (< or > 18-25 kg/m2)

Systemic autoimmune disease

Atopic diseases(e.g., asthma and eczema)

Chronic pain syndromes (e.g., chronic fatigue syndrome and fibromyalgia)

Neuropsychiatric diseases

Table 4 Donor screening for fecal microbiota transplantation

Common and entail serologic screening items[32,124]

Blood routine

Blood biochemistry

Human immunodeficiency virus-1 and -2

Hepatitis A, B and C virus

Syphilis

Helicobacter pylori

Human T lymphotropic virus

Cytomegalovirus

Epstein-barr virus

Common and entail stool screening items[32,124]

Stool routine

Clostridium difficile toxin A/B

Salmonella sp.

Shigella sp.

Campylobacter sp.

Escherichia coli O157

Staphylococcus aureus

Yersinia

Helicobacter pylori

Vibrio parahaemolyticus and Vibrio cholerae

Candida albicans

Rotavirus

Cryptosporidium

Giardia

Cyclospora

Isospora

Ova and parasites