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Research on gut microbiota has generally focused on fecal samples, representing luminal content of the large intestine. However, nutrient uptake is restricted to the small intestine. Abundant immune cell populations at this anatomical site combined with diminished mucus secretion and looser junctions (partly to allow for more efficient fluid and nutrient absorption) also results in intimate host-microbe interactions despite more rapid transit. It is thus crucial to dissect key differences in both ecology and physiology between small and large intestine to better leverage the immense potential of human gut microbiota imprinting, including probiotic engraftment at biological sensible niches. Here, we provide a detailed review unfolding how the physiological and anatomical differences between the small and large intestine affect gut microbiota composition, function, and plasticity. This information is key to understanding how gut microbiota manipulation, including probiotic administration, may strain-dependently transform host-microbe interactions at defined locations.

Research on gut microbiota has generally focused on fecal samples, representing luminal content of the large intestine. However, nutrient uptake is restricted to the small intestine. Abundant immune cell populations at this anatomical site combined with diminished mucus secretion and looser junctions (partly to allow for more efficient fluid and nutrient absorption) also results in intimate host-microbe interactions despite more rapid transit. It is thus crucial to dissect key differences in both ecology and physiology between small and large intestine to better leverage the immense potential of human gut microbiota imprinting, including probiotic engraftment at biological sensible niches. Here, we provide a detailed review unfolding how the physiological and anatomical differences between the small and large intestine affect gut microbiota composition, function, and plasticity. This information is key to understanding how gut microbiota manipulation, including probiotic administration, may strain-dependently transform host-microbe interactions at defined locations.

Free fatty acid receptor-4 (FFAR4), also known as GPR120, has been reported to mediate the beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) by inducing an anti-inflammatory immune response. Thus, activation of FFAR4 has been reported to ameliorate chronic low-grade inflammation and insulin resistance accompanying obesity. However, conflicting reports on the role of FFAR4 in mediating the effects of ω3-PUFAs are emerging, suggesting that FFAR4 may not be the sole effector. Hence analyses of the importance of this receptor in relation to other signaling pathways and prominent effects of ω3-PUFAs remain to be elucidated. In the present study, we used Ffar4 knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucrose ω3-PUFA; or high fat, high sucrose ω6-PUFA diet for 36 weeks. We demonstrate that both KO and HET mice fed ω3-PUFAs were protected against obesity, hepatic triacylglycerol accumulation, and whole-body insulin resistance. Moreover, ω3-PUFA fed mice had increased circulating protein levels of the anti-inflammatory adipokine, adiponectin, decreased fasting insulin levels, and decreased mRNA expression of several proinflammatory molecules within visceral adipose tissue. In conclusion, we find that FFAR4 signaling is not required for the reported anti-inflammatory and insulin-sensitizing effects mediated by ω3-PUFAs.

The obesity epidemic seems to increase at an alarming pace with the concomitant rise in comorbidities, not only hampering life quality of the individual, but also enduring a massive economic burden for society. Consequently, the search for new strategies in combating obesity and its associated sequelae are of huge interest. The chronic low-grade inflammation accompanying obesity has been established as an important driver of the often related development of insulin resistance. Hence, limiting inflammation could impede this deterioration, curbing the risk for progression towards type 2 diabetes. The discovery that G-protein coupled receptor (GPR)120 mediated insulin-sensitizing and anti-inflammatory effects of long chain omega-3 polyunsaturated fatty acids (ω3-PUFAs), thrusted this receptor to the forefront of obesity research as a potential drug target. Nevertheless, conflicting reports on the importance of GPR120 appear to emerge, hence the hierarchy of this signaling pathway in relation to other well-established prominent effects of ω3-PUFAs remain to be elucidated. In the present study, we used a high fat diet-fed mouse model comprising GPR120 knock outs (KO) and heterozygotes (HET) fed either a low fat (LF), high fat fish oil (FO) or high fat soy oil diet (SO) for 36 weeks. During this period, weight and feed intake were monitored, and insulin and glucose tolerance tests were performed. Subsequently, various immunological and metabolic markers were investigated by RT-qPCR to elucidate genotypic differences. Interestingly, we demonstrate that FO-fed mice are protected against obesity development, steatosis, and insulin resistance. Additionally, FO-fed mice had increased adiponectin levels and decreased fasting insulinaemia. Still, mice exhibited glucose intolerance alongside increased insulin secretion, suggesting a pre-diabetic state. This correlated with diminished Glut4 expressions in adipose tissues. Most importantly, none of these effects wer