No abstract

Background During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice. Methods Fecal and blood samples from adult (n = 42, 100–300 days) and aging (n = 32, 550–750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin. Results We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces. Conclusions We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.

Here, we show a connection between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. Specifically, we show that the mild colitis symptoms seen in IL-1α-deficient mice following administration of DSS are correlated with the unique gut microbiota compositions of the mice. However, when these mice are exposed to WT microbiota by cohousing, their gut microbiota composition returns to resemble that of WT mice, and their disease severity increases significantly. As inflammatory bowel diseases are such common diseases, with limited effective treatments to date, there is a great need to better understand the interactions between microbiota composition, the immune system, and colitis. This study shows correlation between microbiota composition and DSS resistance; it may potentially lead to the development of improved probiotics for IBD treatment.

How do stressful life events increase the risk for autoimmune disorders? Here we show that chronic social stress in mice promotes the expression of virulent genes in the gut microbiota and alters the microbial translocation into the mesenteric lymph nodes. Our results also suggest that the consequent immune response to the stress-affected microbiota may endanger the tolerance for self. The presence of specific translocated bacteria and the immune response in the mesenteric lymph nodes can be diminished using an inhibitor of the bacterial communication system without drastically affecting the gut microbial composition as antibiotics do.

Rheumatoid arthritis (RA) is characterized by chronic autoinflammation of the joints, with a prevalence of about 1% in Western populations. Evidence in recent years has linked RA to changes in the gut microbiota (dysbiosis). Interestingly, helminths have been shown to have therapeutic activity in RA. Specifically, a glycoprotein containing phosphorylcholine (PC) extracted from helminths was found to have immunomodulatory activity. We have previously developed a novel chimeric compound composed of tuftsin-PC (TPC) that attenuates the joint destruction in mice with collagen-induced arthritis (CIA). Here, we address the interrelationship between TPC immunomodulatory activity and the gut microbiota in CIA mice. Preventive therapy with TPC in mice with arthritis maintained a physiological arthritis score as well as a steady gut microbial environment, similar to that of healthy controls, in contrast to CIA mice with severe disease. The microbial composition differed significantly between healthy and phosphate-buffered saline-treated CIA mice, enabling classifying test samples by machine learning based on levels of a small number of bacterial species. Using these bacterial biomarkers, all TPC-treated CIA mice were classified as healthy. Thus, we describe a clear correlation between TPC treatment, healthy gut microbial communities, and prevention of arthritis. This is the first study to demonstrate the immunomodulatory effect of helminth derivatives in autoimmune diseases and the link to gut microbiota.