GUT MICROBIOTA AS A

TARGET FOR
PERSONALIZED NAFLD
INTERVENTIONS

Sofia Kirke Forslund

@inanna_nalytica
Host-microbiome interaction in disease risk and progression
Host-microbiome interaction in disease risk and progression
Host-microbiome interaction in disease risk and progression
Host-microbiome interaction in disease risk and progression
Host-microbiome interaction in disease risk and progression
High-throughput systems medicine
FATMAL
Rodent model for varying proportions of dietary fats

Schoeler et al.,
MS in preparation
 Rodent model for varying proportions of dietary fats
FATMAL Phenotype impacts

Schoeler et al.,
MS in preparation
 Rodent model for varying proportions of dietary fats
FATMAL
Microbiome impacts

Schoeler et al.,
MS in preparation
 Rodent model for varying proportions of dietary fats
FATMAL
Microbiome impacts

Schoeler et al.,
MS in preparation
 Rodent model for varying proportions of dietary fats
FATMAL
Microbiome vs hepatic gene regulation

Schoeler et al.,
MS in preparation
 Rodent model for varying proportions of dietary fats
Transfer of diet-induced microbiome improves steatotic phenotype
FATMAL

Schoeler et al.,
MS in preparation
 Moderate but present association between consumption of
different types of fat and gut microbiome composition in a
FATMAL
human cohort

Schoeler et al.,
MS in preparation
 Moderate but present association between consumption of
different types of fat and gut microbiome composition in a
FATMAL
human cohort

Schoeler et al.,
MS in preparation
Approach for confounder-aware search for treatment
efficacy drivers in a nutritional intervention

Collaborators on CORONA:
Müller/Dechend lab
(MDC/Charité), Wilck lab
(Charité), Kleinewietfeld lab
(VIB), Linker lab (MDC/Charité),
Michalsen lab (Immanuel-
Krankenhaus)…

"Fasting alters the gut microbiome

reducing blood pressure and body weight
in metabolic syndrome patients ", Maifeld,
Nature Communications 2021
 Approach for confounder-aware search for treatment
efficacy drivers in a nutritional intervention


Intervention by 1-week Buchinger fasting
followed by DASH diet

Control group on DASH diet only

Microbiome + host phenotyping + immune
cell cytometry

Maifelt et al., Nat Comm 2021

 Approach for confounder-aware search for treatment
efficacy drivers in a nutritional intervention

Microbiome and immunome shift distinctly upon fasting and revert upon its
cessation (multivariate analysis)

Maifelt et al., Nat Comm 2021

 Approach for confounder-aware search for treatment
efficacy drivers in a nutritional intervention

Microbiome and immunome shift distinctly upon fasting and revert upon its
cessation (multivariate analysis)

Maifelt et al., Nat Comm 2021

Approach for confounder-aware search for treatment
efficacy drivers in a nutritional intervention

Strong phenotype effect even accounting for treatment changes

Maifelt et al., Nat Comm 2021

Approach for confounder-aware search for treatment
efficacy drivers in a nutritional intervention

Fasting appears to deplete

commensals (including
butyrate producers) and enrich
for pathobionts, with changes
reversing during re-feeding

Maifelt et al., Nat Comm 2021

Approach for confounder-aware search for treatment
efficacy drivers in a nutritional intervention

Treatment responders
(improvement in BP and/or
reduced need for anti-HTA
medication) have
characteristic microbiome
features which fasting
normalizes

Maifelt et al., Nat Comm 2021

 Evidence for fasting-induced microbiome changes
possibly enhancing hepatic health

Other available human

studies of fasting and calory
restriction (mostly lower-
resolution and smaller scale)
support core signature we
demonstrated

Forslund, Journal of Internal Medicine, in revision

Planned/ongoing clinical trial of an isocaloric dietary
intervention in a population at risk for NAFLD
Host-microbiome factors in cardiovascular disease team
Further directions?