Transient intestinal infections affect host adaptation to nutritional restriction

Recent PNAS Studies have revealed that transient intestinal infection not only promotes white adipose tissue (WAT) expansion and host weight gain, but also optimizes host carbohydrate metabolism.

study: Infection-induced microbiota facilitate host adaptation to nutrient limitation. Image credit: mi_viri / Shutterstock.com

Metabolism and Gut Microbiota

The human gut microbiota plays an important role in host physiology and fitness by regulating the metabolism and immune system. Additionally, these microbes extract energy through biochemical reactions of proteins, fats and carbohydrates obtained from the human diet.

Several studies have shown the versatile ability of the human microbiome to rapidly adapt to dietary changes. Therefore, human diet is one of the main determinants of microbiome diversity and metabolic output.

The gut microbiota diversity of malnourished hosts differs significantly compared to hosts accustomed to a high-fat Western diet. Fat-rich diets raise triglycerides and blood sugar levels, which, along with body fat, increase the risk of diabetes and other health problems. regulates the host’s use and storage of dietary energy.

In particular, host metabolism can be favorably or adversely regulated by the presence of specific taxa within the microbiome.For example, mucolytic bacteria Akkermansia muciniphila It protects the host from obesity and diabetes. vice versa, Bilophila Wadswazia Rapidly proliferates in response to fat-induced bile acids and enhances metabolic syndrome.

In addition to diet, infections and antibiotic treatments also affect the diversity of the host microbiome. For example, overuse of antibiotics is strongly associated with decreased gut microbiota diversity and associated increased prevalence of various inflammatory and metabolic diseases.

Exposure to a few pathogens has been found to be beneficial to the host by improving the host’s health. This discovery live Experiments using wild and laboratory mice revealed that wild mice, which are frequently exposed to a wide range of pathogens, are less susceptible to influenza infection, colon cancer, obesity, and metabolic syndrome than laboratory mice. became.

Although dysregulated host metabolism can alter microbiota resistance to pathogens, the potential impact of infection on microbiota regulation of host metabolism is clear.

About research

In the current study, the impact of infection on host metabolism was assessed using: Yersinia pseudotuberculosis (Yptb) A model of transient intestinal infection. Yptb is a food-borne bacterium that causes transient weight loss in infected mice before being cleared from the gut and peripheral tissues within 4 weeks after infection.

Fifteen weeks after infection, convalescent mice began to gain significantly more weight than untreated controls. However, this weight gain was not related to food intake.

Investigation result

X-ray imaging of Yptb-infected mice 15 weeks post-infection revealed a significant expansion of peripheral body fat. Weight gain was observed in her three major WAT depots: mesenteric, perigonadal, and subcutaneous.

Higher circulating levels of adiponectin, a hormone secreted by WAT, were found in Post-Yptb mice. WAT expansion may result from increased adipocyte size and proliferation of progenitor cells.

Evaluation of the proliferation marker Ki-67 at 4 weeks after Yptb revealed the presence of adipocyte progenitor cells in the mesentery and perigonads, but not in subcutaneous WAT. Similar her Ki-67 expression was not seen in naive control mice. This highlights the role of Ki-67 on increasing adipocyte hyperplasia. These findings suggest that previous intestinal infection can stimulate physiological remodeling of WAT and promote long-term weight gain after pathogen clearance.

The authors also showed that infection-induced gut microbiota can alter host metabolism to use carbohydrates, resulting in elevated glucose disposal, weight gain, and expanded WAT. also observed. Carbohydrate metabolism optimized for this type of infection can also promote host fitness and prevent malnutrition based on limited protein and fat availability.
Therefore, previous infections appear to promote resistance to malnutrition, especially when malnutrition is caused by limited consumption of protein and fat.

Consistent with previous reports, the findings of the current study highlight the importance of environmental stressors for fully developing and optimizing host physiology. Nevertheless, the authors were unable to elucidate mechanisms associated with infection-induced microbiota in distal tissue changes such as WAT and systemic physiology (carbohydrate metabolism). To further develop these findings, the authors now investigate how parastellar-associated molecular patterns (MAMPs) and/or metabolites synergize to promote host metabolism long after infection. doing.

Conclusion

The current study has elucidated the role of previous infections in mediating host adaptation to nutrient instability. Importantly, infection-induced gut microbiota was found to optimize host metabolism towards carbohydrate utilization.

In resource-poor settings where infections and undernutrition are prevalent, infection-optimized carbohydrate metabolism may be adapted. A Western diet can make them maladjusted.