Finally, we documented a wide association between the GM, behavior, BDNF, and the immune system, and although not stating causality, the present study emphasizes the need for more research into the impact of the GM on behavior both in general and in disease. Although Salmonella is a Gram-negative organism, the clinical picture and inflammatory response in systemic Salmonella infections differs from that in other Gram-negative sepsis. This is most likely due to the behaviour of Salmonella as facultative intracellular pathogens, and to the fact that the pattern of cytokine induction differs from other Gram-negative infections. In mice, TNFa is undetectable in the circulation until several days after S. typhimurium infection, whereas TNFa rises at 1 hour after extracellular Gram-negative infection. The level of cytokinemia during Salmonella infections does not reach the toxic levels seen in endotoxic shock, and inhibition of TNFa during Salmonella infection worsens the outcome. Considering these differences in the pathogenesis of Salmonella and extracellular Gram-negative infections, one would envisage either beneficial effects of lipoproteins on the host resistance to Salmonella through blockade of cellular internalization, or deleterious effects by blocking the induction of cytokines by Salmonella LPS that are required for the activation of host defense. In the present study, we investigated the effect of lipoproteins on the outcome of Salmonella infection. In the present study, we demonstrate that hyperlipoproteinemic mice are resistant against S. typhimurium infection. The protection was not due to the absence of the LDLR in the knock-out mouse strain, but to a direct effect of hyperlipoproteinemia. The beneficial effect of lipoproteins was exerted by blocking the interaction of Salmonella with host cells, including endothelial cells and monocytes, which led to inhibition of organ invasion. This resulted in an altered distribution of the microorganism to the organs of the host, and increased survival. It has previously been shown that lipoproteins bind and neutralize LPS, with beneficial effects in Gram-negative infections. As S. typhimurium is an LPS-containing Gram-negative bacterium, and Salmonella LPS plays a crucial role in cytokine stimulation and induction of mortality in vivo, an improved survival of LDLR2/2 mice during systemic S. typhimurium infection would have been expected.