Xylo-Oligosaccharides in Prevention of Hepatic Steatosis and Adipose Tissue Inflammation: Associating Taxonomic and Metabolomic Patterns in Fecal Microbiomes with Biclustering.

Jukka Hintikka,Sanna Lensu,Satu Pekkala,Marjaana Honkanen,Sira Karvinen,Jere Lindén,Tim Garrels,Leo Lahti,Elina Mäkinen

doi:10.3390/ijerph18084049

Abstract

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

Highlights

Up to 90% of the obese population in Western countries is estimated to suffer from non-alcoholic fatty liver disease (NAFLD)
We and others have found that the growth of F. prausnitzii can be naturally increased by feeding it with prebiotic xylo-oligosaccharides (XOS) [5,7] and we further found that XOS
We found a decent coherence within the biclusters considering the ontology and structure of the metabolites

Summary

Introduction

Up to 90% of the obese population in Western countries is estimated to suffer from non-alcoholic fatty liver disease (NAFLD). NAFLD is defined as excessive fat accumulation in the liver, which is not caused by excessive alcohol consumption or steatogenic drug use. Simple NAFLD can progress to steatohepatitis, which is characterized by steatosis along with inflammation and hepatocyte degeneration, and cirrhosis, exposing the patient to a risk of hepatic failure and hepatocellular carcinoma [1]. The pathogenesis of liver diseases has been shown to involve the digestive system and in particular the microbes that it hosts [2]. A very likely explanation could be the flux of microbial metabolites into the portal circulation, facilitated by inflammation in the gastrointestinal tract [3].

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