Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice

Article in Nature Communications, June 7, 2021

Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice. 

Here, we show that a mixture more representative of the complex composition of dietary protein consumed by humans in western societies promotes distinct metabolic perturbations, such as increased weight gain and insulin resistance, compared to a diet containing only casein and we explore the potential role of the gut microbiota in these effects. More specifically, we show the impact of consuming mixed dietary proteins compared to casein on liver metabolism through incomplete mitochondrial oxidation of fatty acids, as well as the activation of the mTORC1/S6K1 signaling pathway. These findings highlight the importance of considering protein sources in the diet of animal models of diet-induced obesity.

To the article in Nature Communications

Developmental trajectory of the healthy human gut microbiota during the first 5 years of life

Article in Cell Host & Microbe, March 31, 2021

The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota is still relatively unknown. Josefine Roswall, Lisa Olsson et al analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory.

To the article in Cell Host & Microbe

The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study

Article published in Cell Metabolism Volume 32, Issue 3, 1 September 2020

Wu et al. showed the link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D.

To the article in Cell Metabolism, July 10, 2020


Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Article in Nature Communications, 18 November, issue 11, 2020

Molinaro et. al show that imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.

In summary, our data suggest that an unhealthy diet may contribute to an altered microbial community type with increased potential to metabolize dietary histidine to ImP, which in turn contributes to impaired glucose metabolism by activating MAPK signaling leading to degradation of insulin receptor substrate and inflammatory signaling. Since ImP has been observed to be increased in subjects with glucose intolerance and type 2 diabetes of several origins, personalized dietary recommendation or inhibition of urdA might be helpful for reducing circulating ImP levels.

To article in Nature Communications

Microbial imidazole propionate affects responses to metformin through p38γ - dependent inhibitory AMPK phosphorylation

Short article in Cell Metabolism October, Volume 32, issue 4, 2020

Koh et al. show that imidazole propionate, a microbial metabolite, impairs the glucose-lowering effect of the antidiabetic drug metformin and inhibits metformin-induced AMPK activation by activating p38γ/Akt/inhibitory AMPK serine phosphorylation. They further show that metformin action is restored by blocking imidazole propionateactivated p38γ.

To the article published in Cell Metabolism

Gut microbial metabolites as multi-kingdom intermediates

Review article in Nature Reviews Microbiology, 23 September 2020

Bäckhed et. al discuss major microbial metabolites, highlight how they affect host health & provide a framework for integrating discovery-based metabolite studies with mechanistic work.

To the review published in Nature Microbiology


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