Microbially produced imidazole propionate is associated with heart failure and mortality

Open access article online, JACC Heart Failure, April 2023

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


6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice

Article, Gut, February 2023

In this article, Kassem Makki et al, show that modulation of the gut microbiota with oligofructose enriches bacteria involved in 6α-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.

This article was first published online in June 2023 and was published in Gut, issue 72, February 2023.
To the article: Feb;72(2):314-324, 2023

The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease

Review article, Nat Rev Cardiol, 14 Oct 2022

In this review, Rima Chakaroun, Lisa Olsson, Fredrik Bäckhed provide an overview of the current evidence on the interconnectedness of the gut microbiome and CVD against the noisy backdrop of highly prevalent confounders in advanced CVD, such as increased metabolic burden and polypharmacy. We further aim to conceptualize the molecular mechanisms at the centre of these associations and identify actionable gut microbiome-based targets, while contextualizing the current knowledge within the clinical scenario and emphasizing the limitations of the field that need to be overcome.


To the full article in Nature Reviews Cardiology

Microbiome-derived ethanol in nonalcoholic fatty liver disease

Article, Nature Medicine 10 Oct, 2022

Fredrik Bäckhed is one of the Co-authors of this article were it is concluded that the human gut microbiota produces large amounts of ethanol that might be clinically relevant for the pathogenesis of NAFLD. Ethanol production during an MMT should be considered as a noninvasive diagnostic approach for the detection of gut microbiota producing high levels of ethanol and NAFLD risk. In our prospective cohort, high postprandial plasma ethanol concentrations correlated particularly with high relative fecal abundance of lactic acid bacteria. Clinical trials targeting the gut microbiome have not yielded any meaningful outcome in NAFLD thus far. To what extent persistent endogenous ethanol production is causally involved in the highly complex pathogenesis of NAFLD, where a combination of environmental factors, genetic variants, obesity and disturbed lipid homeostasis interact, remains to be elucidated. Nevertheless, our findings suggest that further attention aiming to target the gut microbiota to reduce ethanol production and thereby lower additional risk for NAFLD is justified.

To the full article in Nature Medicine


Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden

Article, Cell Host & Microbe, April 28, 2022

In this study, Lisa Olsson, Valentina Tremaroli and co-authors, investigated the temporal dynamics and the extent of intra- and inter-individual variation for the composition and functional potential of the normal gut microbiota. Our analyses showed that the intra-individual variation accounted for a large portion of the total variation in gut microbiota composition (23%) and that several functional pathways were highly dynamic (median ICC ≈ 0.5).

However, we observed that the extent of intra-individual compositional variation was individual specific and lower in communities with high relative abundance of F. prausnitzii, B. longum, and B. breve, as well as with low temporal variation of F. prausnitzii and low abundance of the ato terminal gene for butyrate synthesis. We noted that all communities, both stable and variable, displayed occasional blooming of species and potential functions belonging to Enterobacteriaceae and other facultative anaerobic or aerotolerant bacteria. Therefore, our results suggest that these fluctuations are part of normal gut microbiota dynamics and homeostatic interaction with the host.

To the article


6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice

Open access article online, Gut, 14 June, 2022

In this online article, Kassem Makki and co-authors demonstrate how fiber supplementation increases microbial production of 6a-hydroxylated bile acids, which improve glucose metabolism through tgr5 induced GLP1 production.

To the article in Gut online


The metabolic role and therapeutic potential of the microbiome

Review article, Endocrine Reviews, 30 January 2022

In a recent review Louise Olofsson and Fredrik discuss how the gut bacterial composition is altered in, and may contribute to, cardiometabolic disease, as well as how the gut bacteria can be targeted to treat and prevent metabolic diseases.

To the review published in Endocrine Reviews

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