A recent one PNAS study reveals that transient intestinal infection not only promotes white adipose tissue (WAT) expansion and weight gain, but also optimizes host carbohydrate metabolism.
Examination: Infection-induced microbiota promote host adaptation to nutrient restriction. Image credit: mi_viri / Shutterstock.com
Metabolism and the gut microbiome
The human gut microbiome plays a critical role in host physiology and fitness by regulating metabolism and the immune system. In addition, these microbes extract energy through biochemical reactions of proteins, fats and carbohydrates obtained from the human diet.
Several studies have indicated the versatile ability of the human microbiome to rapidly adapt to dietary changes. Therefore, the human diet is one of the main determinants of microbiome diversity and metabolic production.
The gut microbiome diversity of malnourished hosts is significantly different compared to those accustomed to a high-fat Western diet. A diet high in fat increases triglycerides and blood sugar levels, along with body fat, which in turn increases the risk of diabetes and other health problems. Although an individual’s diet determines the microbial diversity in the gut, these microbes regulate the host’s use and storage of dietary energy.
In particular, host metabolism can be positively or detrimentally regulated by the presence of specific taxa in the microbiome. For example, the mucus-degrading bacteria Akkermansia muciniphila protects the host from obesity and diabetes. Vise versa Bilophila wadsworthia grow rapidly in response to fat-induced bile acids to exacerbate metabolic syndromes.
In addition to diet, infections and antibiotic treatments also affect host microbiome diversity. For example, overuse of antibiotics has been strongly associated with reduced gut microbiota diversity, which has been associated with the increased incidence of various inflammatory and metabolic diseases.
A small degree of pathogen exposure was shown to be beneficial to the host by improving the host’s fitness. This finding was confirmed by a Direct experiment with wild mice and laboratory mice, which revealed that wild mice, which are more frequently exposed to a wide range of pathogens, are less affected by influenza infection, colon cancer, obesity and metabolic syndromes compared to laboratory mice.
Although dysregulated host metabolism can alter microbiota resistance to pathogens, the potential impacts of infection on microbiota regulation of host metabolism remain clear.
About the study
In the current study, the effect of infection on host metabolism was assessed using Yersinia pseudotuberculosis (Yptb) model of transient intestinal infection. Yptb, a foodborne bacterium, causes transient weight loss in infected mice before being cleared from the gut and peripheral tissues within four weeks of infection.
At fifteen weeks post-infection, convalescent mice began to gain significantly more weight than naïve control mice. However, this increase in weight was not related to food intake.
Radiographs of Yptb-infected mice fifteen weeks after infection revealed a significant expansion of peripheral body fat. The weight gain was observed in three main WAT depots, namely mesenteric, perigonadal and subcutaneous.
A higher circulating level of adiponectin, a hormone secreted by WAT, was found in Post-Yptb mice. WAT expansion can be attributed to an increase in the size of adipocytes and the proliferation of progenitors.
Assessment of the proliferation marker Ki-67 four weeks after Yptb revealed the presence of adipocyte progenitors in mesenteric and perigonadal but not in subcutaneous WAT. Similar Ki-67 expression was not found in the naïve control mice, highlighting the role of Ki-67 in increased adipocyte hyperplasia. These results suggest that prior intestinal infection may stimulate the physiological remodeling of WAT and promote long-term weight gain after pathogen clearance.
The authors also observed that infection-induced gut microbiota could alter host metabolism to utilize carbohydrates, resulting in elevated glucose disposal, weight gain, and WAT expansion. This type of infection-optimized carbohydrate metabolism could also promote host fitness based on limited availability of protein and fat and prevent malnutrition.
Thus, previous infection appears to promote resistance to malnutrition, especially if the malnutrition was caused by limited consumption of proteins and fats.
Consistent with previous reports, the results of the current study underscore the importance of environmental stressors to fully develop and optimize host physiology. Nevertheless, the authors failed to elucidate the mechanism associated with infection-induced microbiota altering distal tissues such as WAT and systemic physiology (carbohydrate metabolism). To extend these findings, the authors are currently investigating how Parasutterella-associated molecular patterns (MAMPs) and/or metabolites synergize to promote host metabolism long-term after infection.
The present study elucidated the role of prior infection in mediating host adaptation to nutrient precarity. Importantly, infection-induced gut microbiota was shown to optimize host metabolism toward carbohydrate utilization.
In underresourced environments where infection and nutrient deficiency are prevalent, infection-optimized carbohydrate metabolism may be adaptive. However, infection-induced carbohydrate metabolism may be maladaptive in a ketogenic or high-sugar Western diet.
- Siqueira, DMK, Andrade-Oliveira, V., Stacy, A., et al. (2023) Infection-induced microbiota promotes host adaptation to nutrient restriction. PNAS 124(4) doi:10.1073/pnas.2214484120