Mechanistic insights into the attenuation of intestinal inflammation and modulation of the gut microbiome by krill oil using in vitro and in vivo models

Abstract

Background: The anti-inflammatory property of ω-3 polyunsaturated fatty acids (PUFA) has been exploited in the management of inflammatory bowel disease (IBD) with promising results. However, it remains unclear if PUFA play a significant role in the resolution of inflammation and promotion of mucosal healing. Krill oil (KO) is a natural product rich in PUFA and the potent antioxidant, astaxanthin. In this study, we attempted to understand the mechanisms through which KO modulates the gut microbiome and metabolome using in vitro and in vivo colitis models and a multi-omics based approach. Results: KO significantly decreased LPS-induced IL1β and TNFα expression in human macrophages in vitro in a dosedependent manner by regulating a broad spectrum of signaling pathways, including NF-κB and NOD-like receptor signaling, and displayed a synergistic effect with COX2 and IKK2 inhibitors in attenuating inflammatory pathways. Moreover, KO was involved in the resolution of inflammation by promoting M2 polarization and enhancing macrophagemediated intracellular bacterial killing. Parasite-dependent intestinal mucosal damage and microbial dysbiosis induced by Trichuris suis infection in pigs were partially restored by feeding KO. KO supplementation reduced the abundance of Rickettsiales and several species of Lactobacillus, which were among the important features identified by random forests analysis contributing to classification accuracy for KO supplementation. Several microbial signatures with strong predictive power for the status of both infection and supplementation were identified. The inhibitory effect of KO on histidine metabolism was identified using untargeted metabolomics. KO supplementation reduced several key metabolites related to histamine metabolism by suppressing the expression of a gene encoding L-histidine decarboxylase in the colon mucosa and reducing histamine biosynthesis of microbial origin. Moreover, the pro-resolving properties of KO were validated using a Citrobacter rodentium-induced Th1-dependent colitis murine model. Further, microbial signatures with high prediction accuracy for colitis-related pathophysiological traits were identified in mice.

Molecular and metabolomic changes in the proximal colon of pigs infected with Trichuris suis

“…Evidence is mounting that these metabolic features are microbiome-dependent and contribute to the control of infection and level of inflammation in pigs 16,17 but are also relevant to intestinal inflammation in humans 106,107 . Recent evidence has shown that other dietary components such as omega-3-enriched krill oil can enhance the diversity of the intestinal microbiome and level of inflammation in pigs infected with T. suis 108 . Dietary interventions that modulate metabolic and infectious diseases that are also important in humans have been used successfully in pigs supplemented with defined micro-and macro-nutrients 109,110 , phytonutrients 111 and probiotics 112 as well as more complex food matrices that also effect change in microbiome linked to disease outcome (Solano-Aguilar et al, in review).…”

The gut microbiome in differential diagnosis of diabetic kidney disease and membranous nephropathy

“…We found an increase in the aerobic metabolism module, containing amino acid metabolism (alanine, aspartate and glutamate) and the citrate cycle; this result indicated the potential of the microbial environment to shift toward more aerotolerant conditions ( Table S4 ). We also observed overexpression of histidine metabolism in DKD; its product histamine might be involved in mediating the inflammatory response [ 51 ]. ABC transporters mediate the transport of hydrophilic compounds and promote the growth of various bacteria, such as Mycobacterium tuberculosis [ 52 ].…”

Diet-induced Changes in Bacterial Communities in the Jejunum and Their Associations with Bile Acids in Angus Beef Cattle

“…Amplicons were nally puri ed using Agencourt AMPure XP bead kits (Beckman Coulter Genomics, Danvers, MA). The library pool was sequenced in an Illumina MiSeq sequencer with an Illumina MiSeq Reagent Kit according to a protocol previously described [36].…”