Table 4.
Overview of the Infectious Diseases or Patient Groups With Risk of Infectious Disease in Which the Microbiome Has Been Targeted for Prevention or Treatment and Tested in Human Clinical Trials
| Patient Category | Disease | Target and Known Effects | Key Refs. |
|---|---|---|---|
| Critically ill, adult | VAP | SDD for the prevention of respiratory tract infections. Probiotics for the prevention of VAP. Moderate evidence supports the indication. | [1, 2] |
| Mortality | SDD and probiotics for the prevention of mortality. Strong evidence for SDD. No conclusions possible based on limited evidence for probiotics. | [2–5] | |
| Critically ill, neonatal | Necrotizing enterocolitis | Probiotics for the prevention of NEC. Strong evidence supporting derived from meta-analyses supporting probiotics for prevention of NEC severity and mortality. However, recent RCT, not included in the meta-analysis, showed no benefit of probiotic in NEC. | [6, 7, 39] |
| Candidemia | Probiotics tested for prevention of candidemia, Candida colonization, and candiduria. No conclusions possible based on limited evidence | [8] | |
| Late-onset sepsis | Probiotics for the prevention of late-onset sepsis in preterm infants. Moderate evidence supporting probiotics for the prevention of late-onset mortality. | [7, 9] | |
| Surgical | Trauma | Probiotics for the prevention of “infectious complications” and mortality. SDD for prevention of “infectious complications and mortality”. Heterogeneous studies, with some support for use, no conclusions possible based on limited evidence. | [10, 11] |
| Post-GI surgery | Probiotics for the prevention of infectious complications and mortality. Heterogenous studies, with some support for use. No conclusions possible based on limited evidence. | [12, 13] | |
| Oncology and hematology | HSCT and chemotherapy complications | Microbiome composition and diversity can act as a predictor for the risk of blood stream and other infections. FMT (study ongoing) and probiotics to decrease infectious complications and GvHD—no conclusions possible based on limited evidence to date. | [14–16] |
| Mucositis | Probiotics for the prevention and treatment of chemotherapy and radiation-induced mucositis and diarrhea. Few studies, significant heterogeneity, no conclusions possible based on limited evidence. | [17, 18] | |
| HIV | Disease progression | Probiotics and synbiotics for improvement of immune function. Small, heterogeneous studies, no conclusions possible based on limited evidence. | [19] |
| Diarrhea | Probiotics to decrease diarrhea in HIV patients. Small, heterogeneous studies, no conclusions possible based on limited evidence. | [20] | |
| Upper respiratory | Upper respiratory tract infection | Probiotics for prevention of URTI in children. Small, heterogeneous studies, some support of use, no conclusions possible based on limited evidence. | [21, 22] |
| Gastrointestinal | Clostridium difficile and antibiotic-associated diarrhea | FMT effective as treatment for refractory C difficile. Bacteriotherapy for prevention. Probiotics for prevention. Moderate quality evidence suggests probiotics are safe and effective. | [23–25] |
| Acute infectious gastroenteritis | Probiotics for the prevention and treatment of infectious gastroenteritis. Evidence supports probiotics use in the treatment of persistent diarrhea in pediatric patients and shortening and reducing stool frequency in adults and infants. | [26, 27] | |
| Traveler’s diarrhea | Probiotics for the prevention of traveler’s diarrhea. Limited and inconclusive evidence that probiotics prevent traveler’s diarrhea. | [28, 29] | |
| Amebiasis | Probiotics for the treatment of amebiasis in children. No conclusions possible based on limited evidence. | [30] | |
| Helicobacter pylori | Probiotics for the adjunctive treatment of H pylori. No evidence probiotics improve eradication. | [31] | |
| Spontaneous bacterial peritonitis | Probiotics for the prevention of SBP in patients with ascites. No evidence that probiotics prevent SBP. | [32] | |
| Urogenital | Urinary tract infection | Probiotics for the prevention of (recurrent) UTI. No significant benefit, no conclusions possible based on limited evidence. | [33] |
| Antimicrobial resistance | Multiresistant infections or colonization | FMT for treatment of multidrug-resistant colonization and AMR genes. FMT can reduce antibiotic-resistant organisms and genes, but evidence to date of clinical consequences only in case series and reports. | [34–36] |
| Vaccines | Polio vaccine, rotoavirus vaccine | Antibiotics (azithromycine) to improve oral polio vaccine efficacy showed no effect. There is a significant association between microbiome composition and rotavirus vaccine. | [37, 38] |
Abbreviations: AMR, antimicrobial resistance; FMT, fecal microbiota transplant; GI, gastrointestinal; GvHD, graft-versus-host disease; HIV, human immunodeficiency virus; HSCT, hematopoietic stem cell transplantation; NEC, necrotizing enterocolitis; SBP, spontaneous bacterial peritonitis; RCT, randomized control trial; SDD, selective digestive tract decontamination; URTI, upper respiratory tract infection; UTI, urinary tract infection; VAP, ventilator-associated pneumonia.
NOTE: Please see Supplementary Material for list of references.