Table 3.
Microbiome-Based Targeted Therapies
| Focus | Important Studies | Findings | Barriers |
|---|---|---|---|
| Direct microbiome therapies | |||
| Probiotics | Agrawal et al, 2012142 | Probiotics pre cirrhosis can improve NAFLD histology, in cirrhosis can reduce dysbiosis, and are effective for reversing secondary prevention of OHE, reducing hospitalizations for decompensating events, but may or may not improve cognition (MHE) | Duration of administration, standardization of formulations |
| Bajaj et al, 2014143 | |||
| Dhiman et al, 2014124 | |||
| Duseja et al, 2019121 | |||
| FMT to prevent disease | Philips et al, 2017144 | FMT was safe, reduced Proteobacteria and increased Actinobacteria post FMT, improved liver disease severity, reduced RR for death at 3 mo and improved survival at 1 y in severe AH. In chronic hepatitis B, FMT group showed microbial changes and reduced HBeAg. FMT increased diversity post FMT in all PSC patients with 3 of 10 experiencing a >50% reduction in ALP, reduction in shortterm alcohol craving and consumption, and AUD-related hospitalizations. | More data needed, expertise, cost, safety, and long-term consequences |
| Philips et al, 2018145 | |||
| Ren et al, 2017146 | |||
| Allegretti et al, 2019147 | |||
| Bajaj et al, 202082 | |||
| FMT to prevent decompensation | Bajaj et al, 2017148 | FMT increased diversity and beneficial taxa along with cognition on short-term follow-up. Brain function, hospitalizations, and cirrhosis-related decompensation, including OHE events remained low on long-term follow-up with persistent engraftment. | |
| Bajaj et al, 2017149 | Can be associated with infections if donors are not screened adequately. | ||
| Bajaj et al, 2019155 | |||
| Bajaj et al, 2019129 | |||
| DeFilipp et al, 2020150 | |||
|
| |||
| Microbiome-augmenting strategies | |||
| FXR/FGF19 analogue | Harrison et al, 2020151 | Aldafermin (FGF19 analogue) use for 24 wk resulted in improvement in NASH and fibrosis. | Still in trial phase |
| Dietary | Bajaj et al, 201875 | In the decompensated stage, Turkish patients had higher beneficial taxa, such as Ruminococcaceae and other Clostridiales, and a lower Enterococcaceae vs US-based patient. Vegetable use and Prevotellaceae, which increase with vegetable use were associated with protection from hospitalization in United States, Mexican and Turkish cohorts. | Standardization of diet, cultural differences, harmonization of diet in microbiota studies |
| Cox et al, 2020152 | High protein, high fermented milk products, and greater vegetables were associated with better outcomes | ||
| Bajaj et al, 202076 | |||
| Periodontal therapy/cleaning | Bajaj et al, 2018153 | In patients with HE there was reduction in Enterobacteriaceae and Streptococcaceae, increase in Ruminococcaceae in stool microbiome and reduction in cirrhosis salivary Pasteurellaceae and Streptococcaceae post periodontal cleaning. | Larger-scale data needed; dental coverage is limited or not emphasized. |
ALP, alkaline phosphatase; FGF, fibroblast growth factor; HBeAg, hepatitis B e antigen; OHE, overt hepatic encephalopathy; PSC, primary sclerosing cholangitis.