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Gut microbes control the body's thermostat

Summary: In both healthy people and those with life-threatening infections, the gut microbiome appears to help regulate body temperature.

Source: University of Michigan

What is considered normal body temperature varies from person to person, but overall, the average basal temperature of the human body has decreased since the 1860s for unknown reasons. One study points to the gut microbiome as a potential regulator of body temperature, both in health and during life-threatening infections.

The study, led by Robert Dickson, MD, and his colleagues at the UM Medical School, used data from health records of patients hospitalized with sepsis and mouse experiments to examine the interaction between the mix of bacteria residing in the gut, temperature fluctuation and health outcomes. .

Sepsis, the body’s response to a life-threatening infection, can cause drastic changes in body temperature, the trajectory of which is linked to mortality.

Work published in American Journal of Respiratory and Critical Care Medicine in 2019 demonstrated that patients hospitalized with sepsis vary widely in their temperature responses, and this variation predicts their survival.

“There’s a reason why temperature is a vital sign,” said Kale Bongers MD Ph.D., clinical instructor in the Department of Internal Medicine and lead author of the study. “It is easily measured and gives us important information about the inflammatory and metabolic state of the body.”

However, the causes of this temperature variation, both in sepsis and in health, remain unknown.

“We know that temperature response is important in sepsis because it strongly predicts who lives and who dies,” Dickson said. “But we don’t know what drives this variation and whether it can be modified to help patients.”

To try to understand the cause of this variation, the team analyzed rectal swabs from 116 patients admitted to the hospital. Patients’ gut microbiota varied widely, confirming that it is a potential source of variation.

“Arguably, our patients have more variation in their microbiota than they do in their own genetics,” Bongers said. “Any two patients are more than 99% identical in their own genomes, while they can have literally 0% overlap in their gut bacteria.”

The authors found that this variation in gut bacteria was correlated with patient temperature trajectories in the hospital. In particular, common bacteria of the phylum Firmicutes were most strongly associated with increased febrile response. These bacteria are common, vary between patients, and are known to produce important metabolites that enter the bloodstream and influence the body’s immune response and metabolism.

This shows a diagram of the intestines
Patients’ gut microbiota varied widely, confirming that it is a potential source of variation. The image is in the public domain

To confirm these findings under controlled conditions, the team used mouse models, comparing normal mice with genetically identical mice lacking a microbiome. Experimental sepsis caused dramatic temperature changes in conventional mice, but had a muted effect on the temperature response of germ-free mice. Among mice with microbiome, variation in temperature response was strongly correlated with the same bacterial family (Lachnospiraceae) found in humans.

“We found that the same type of gut bacteria explained temperature variation in both our human subjects and our laboratory mice,” Dickson said. “It gave us confidence in the validity of our findings and gives us a target to understand the biology behind this discovery.”

Even healthy mice without microbiome had lower basal body temperatures than conventional mice. Treating normal mice with antibiotics also lowered their body temperature.

The study highlights an underappreciated role of the gut microbiome in body temperature and may explain the decline in basal body temperature over the past 150 years.

“While we certainly haven’t proven that changes in the microbiome explain the drop in human body temperature, we think it’s a reasonable hypothesis,” Bongers said. “Human genetics have not changed significantly over the last 150 years, but changes in diet, hygiene and antibiotics have had profound effects on our gut bacteria.”

More research is needed to understand whether targeting the microbiome to modulate body temperature can help alter outcome for patients with sepsis.

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Author: Press office
Source: University of Michigan
Contact: Press Office – University of Michigan
Image: The image is in the public domain

Original search: Closed access.
“The gut microbiome modulates body temperature in both sepsis and health” by Kale S Bongers et al. American Journal of Respiratory and Critical Care Medicine


Gut microbiome modulates body temperature in both sepsis and health

Justification: Among patients with sepsis, variation in temperature trajectories predicts clinical outcomes. In healthy individuals, normal body temperature is variable and has consistently declined since the 1860s. The biological underpinnings of this temperature variation in disease and health are unknown.

Goals. Establish and interrogate the role of the gut microbiome in calibrating body temperature.

Methods: We performed a series of translational analyzes and experiments to determine whether and how variation in gut microbiota explains variation in body temperature in sepsis and health. We studied patient temperature trajectories using data from electronic medical records. We characterized the gut microbiota in hospitalized patients using 16S ribosomal RNA gene sequencing. We modeled sepsis using intraperitoneal lipopolysaccharide in mice and modulated the microbiome using antibiotics, germ-free and gnotobiotic animals.

Measures and main results: Consistent with previous work, we identified four temperature trajectories in patients hospitalized with sepsis that predict clinical outcomes. In a separate cohort of 116 hospitalized patients, we found that patients’ gut microbiota composition on admission predicted their temperature trajectories. Compared with conventional mice, germ-free mice reduced temperature loss during experimental sepsis. Among conventional mice, the heterogeneity of the temperature response in sepsis was strongly explained by variation in the intestinal microbiota. Healthy germ-free mice treated with antibiotics had lower baseline body temperatures when compared to controls. The Lachnospiraceae family has been consistently associated with temperature trajectories in hospitalized patients, experimental sepsis, and mice treated with antibiotics.

Conclusions: The gut microbiome is a key modulator of body temperature variation in both health and critical illness and is therefore an important and understudied target for modulating physiological heterogeneity in sepsis.