Transient gut infection influences hosts’ adaptation to nutrient restriction

A recent PNAS study reveals that transient gut infection not only promotes white adipose tissue (WAT) expansion and host weight gain but also optimizes host metabolism for carbohydrates.

Study: Infection-elicited microbiota promotes host adaptation to nutrient restriction. Image Credit: mi_viri /

Study: Infection-elicited microbiota promotes host adaptation to nutrient restriction. Image Credit: mi_viri /

Metabolism and the gut microbiome

The human gut microbiome plays a vital role in the host’s 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 capacity of the human microbiome to adapt to dietary changes rapidly. Hence, the human diet is one of the main determining factors of microbiome diversity and metabolic output.

The gut microbiome diversity of malnourished hosts is significantly different compared to those accustomed to a high-fat Western diet. A diet rich in fat enhances triglycerides and blood glucose levels, along with body fat which, in turn, increases the risk for diabetes and other health problems. Although an individual’s diet determines microbial diversity in the gut, these microbes regulate the host’s use and storage of energy derived from the diet.

Notably, host metabolism can be regulated favorably or detrimentally by the presence of specific taxa within the microbiome. For example, the mucus-degrading bacterium Akkermansia muciniphila protects the host from obesity and diabetes. Conversely, Bilophila wadsworthia rapidly grows in response to fat-induced bile acids to enhance metabolic syndromes.

In addition to diet, infection and antibiotic treatments also affect host microbiome diversity. For example, the overuse of antibiotics has been strongly linked with reduced gut microbiota diversity, which has been associated with the increased prevalence of various inflammatory and metabolic diseases. 

A small degree of pathogenic exposure was found to be beneficial to the host by improving the host's fitness. This finding was corroborated by an in vivo experiment using wild mice and laboratory mice, which revealed that wild mice that are more frequently exposed to a wide range of pathogens are less affected by influenza infection, colon cancer, obesity, and metabolic syndromes as compared with laboratory mice.

Although dysregulated host metabolism can alter the microbiota’s resistance to pathogens, the potential impacts of infection on the microbiota’s regulation of host metabolism remain clear.

About the study

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

After fifteen weeks of the infection, convalescent mice started gaining significantly more weight than naïve control mice. However, this increase in weight was not related to food intake.

Study findings

X-ray imaging of Yptb-infected mice fifteen weeks post-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 at four weeks post-Yptb revealed the presence of adipocyte progenitors in the mesenteric and perigonadal but not in subcutaneous WAT. Similar Ki-67 expression was not found in the naïve control mice, which highlights the role of Ki-67 for increased adipocyte hyperplasia. These findings suggest that prior gut infection can stimulate the physiological remodeling of WAT and promote long-term weight gain after pathogen clearance.

The authors also observed that infection-elicited gut microbiota could shift host metabolism to use carbohydrates, which results in elevated glucose disposal, weight gain, and WAT expansion. This type of infection-optimized carbohydrate metabolism could also promote host fitness based on limited protein and fat availability and prevent malnutrition.
Thus, prior infection appears to promote resistance to malnutrition, particularly if the malnutrition was caused by limited consumption of proteins and fats.

Consistent with previous reports, the current study's findings underscore the importance of environmental stressors for fully developing and optimizing host physiology. Nevertheless, the authors failed to elucidate the mechanism associated with infection-elicited microbiota in altering distal tissues, such as WAT and systemic physiology (carbohydrate metabolism). To expand upon these findings, the authors are currently exploring how Parasutterella-associated molecular patterns (MAMPs) and/or metabolites synergize to promote host metabolism long-term after infection.


The current study elucidated the role of prior infection in mediating host adaptation to nutrient precarity. Importantly, infection-induced gut microbiota was found to optimize host metabolism toward carbohydrate utilization.

In under-resourced settings where infection and nutrient deficiency prevail, infection-optimized carbohydrate metabolism could be adaptive. However, infection-induced carbohydrate metabolism could be maladaptive in a ketogenic or high-sugar Western diet.

Journal reference:
  • Siqueira, D. M. K., Andrade-Oliveira, V., Stacy, A., et al. (2023) Infection-elicited microbiota promotes host adaptation to nutrient restriction. PNAS 124(4) doi:10.1073/pnas.2214484120
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.


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