Sucrose-rich diets promote hepatic de novo lipogenesis (DNL) and steatosis through interactions with the gut microbiota. However, the role of sugar-microbiota dynamics in the absence of dietary fat remains unclear.  In this article, first author Mattias Bergentall with several co-authors from our lab, conclude that sucrose-microbiota interactions and SREBP-1c are required for DNL and hepatic steatosis in the absence of dietary fat. These findings provide new insights into the complex interplay between diet, gut microbiota, and metabolic regulation.

To the article in Molecular Metabolism

Our former team member Alba Carreras and our current team member Katharina Beck are co-authors of this article, studying how ImP produced by the gut microbes promotes the development of atherosclerosis.

Imidazole propionate (ImP), a microbially produced metabolite, is linked to type 2 diabetes. Its effects on endothelial cells and atherosclerotic coronary artery disease were previously unknown. Studies in humans and animals show ImP contributes to endothelial dysfunction and atherosclerosis, indicating ImP metabolism could be a therapeutic target for cardiovascular disease.

To the article in Arteriosclerosis, Thrombosis, and Vascular Biology

Type 2 diabetes (T2D) is influenced by genetic and environmental factors, including the gut microbiome. Recent research in two Swedish cohorts (n=1,167) identified over 500 blood metabolites linked to impaired glucose control, with about one-third associated with an altered gut microbiome. Metabolic disruptions in microbiome–metabolome dynamics may mediate compromised glucose homeostasis. Short-term lifestyle changes, such as diet and exercise, modulated microbiome-associated metabolites. This study suggests the microbiome–metabolome axis as a modifiable target for T2D management, with optimal benefits from lifestyle modifications.

To the article in Nature Medicine

This article on MASLD heterogeneity includes three co-authors from our lab; Rima Chakaroun, Lisa Olsson and Valentina Tremaroli.

Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. This article investigates the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity.

In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies.

To the article in Nature Medicine 

In this article, we focused on the generation of secondary bile acids by 7α-dehydroxylating bacteria and demonstrated that addition of a very low abundant bacteria to a community can change the metabolic output dramatically. We show that Clostridium scindens converts cholic acid into the secondary bile acid deoxycholic acid (DCA) very efficiently even though the abundance of C. scindens is low, but still detectable by digital droplet PCR. We showed that colonization of germ-free female mice with a community containing C. scindens induces DCA production and affects host metabolism. Finally, we also showed that DCA correlates with impaired glucose metabolism and a worsened lipid profile in individuals with type 2 diabetes, which implies that this metabolic pathway may contribute to the development of cardiometabolic disease.

To the article in Nature Communications

In collaboration with Daniel J Drucker at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, we made the surprising observation more than 10 years ago that GLP-1R deficient mice dies. Further work led by our team member Thomas Greiner, with the support from the Mucin Biology Groups at the University of Gothenburg, revealed involvement of goblet cells.

The microbiota increases energy availability through fermentation of dietary fibers to short-chain fatty acids in conventionally raised mice. Energy deficiency in germ-free (GF) mice increases glucagon-like peptide-1 (GLP-1) levels, which slows intestinal transit. To further analyze the role of GLP-1-mediated signaling in this model of energy deficiency, we re-derived mice lacking GLP-1 receptor (GLP-1R KO) as GF. Our findings reveal a heretofore unrecognized role for GLP-1R signaling in the maintenance of colonic physiology and survival during energy deprivation.

To the article in Molecular Metabolism online

In this paper first author Marc Schöler aim to determine how dietary fatty acid composition affects the gut microbiota profile, microbiota-mediated metabolic regulation, and development of hepatic steatosis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and a leading cause of liver-related mortality. Hepatic steatosis, the first step in NAFLD development, is determined by several factors including uptake and disposal of fatty acids, de novo lipogenesis and fatty acid oxidation within the liver. The composition of dietary fatty acids can affect several of these processes.

To the article "The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis" in Nature Communications

In a study that our and Mattias Lorentzon's research groups published in Nature, we isolated Faecalibacterium prausnitzii, a butyrate-producing bacterium with anti-inflammatory properties, together with another bacterium, Desulfovibrio piger. The latter has beneficial effects on Faecalibacterium prausnitzii's growth and butyrate acid production. By then training the oxygen-sensitive Faecalibacterium prausnitzii in a favorable electrochemical environment, we were able to isolate more oxygen-resistant bacteria. We have now been able to show that the bacterial combination is safe for humans and we are now conducting studies to investigate if the addition of these bacteria has beneficial effects on blood sugar control in individuals with pre-diabetes.

To the article "Synergy and oxygen adaptation for development of next-generation probiotics" in Nature online.

This article, by first author Antonio Molinaro, was recently published online in JACC Heart Failure and shows how the gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.

Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure.

In this study, ImP serum was measurements in 2 large and independent clinical cohorts of patients (European [n = 1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. ImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. This article shows that elevated ImP was a significant independent predictor of 5-year mortality.

To the article online