Table 2.

Future directions of microbiome-targeted therapies for hepatic encephalopathy.

	Future directions
Trial design	Patient selection: target specific groups in need of more effective and/or better tolerated intervention (e.g. at high risk of developing recurrent overt HE, or those who do not tolerate lactulose) Primary outcome selection: clinically important primary outcomes such as overt HE, cognitive function, quality of life, or other patient-reported outcomes (microbiome changes may be included as secondary outcome) Translational component: explore mechanism within clinical trials High rigour: minimise bias through blinding, randomisation ± risk stratification; meet enrolment target to achieve adequate power for trial
Microbiome therapy selection	Target gut segment: match route of administration to optimal gut segment (upper vs. lower intestine) for that mechanism Living biotherapeutics: select probiotic consortium with biological actions with potential to reverse HE, determine optimal dose and duration, assess need for antibiotic priming to ensure grafting Faecal microbiota transplant: determine characteristics of ideal donor, optimal dose regimen and preparation
Personalised approach	Patient enterotype: determine baseline microbiome characteristics to match appropriate microbiome therapy Biomarkers of response: identify other biomarkers predictive of response to microbiome therapies

HE, hepatic encephalopathy.