Gut microbes regulate the body’s thermostat

Overview: 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 in general, the average basal temperature of the human body has declined for unknown reasons since the 1860s. A 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 UM Medical School, used health record data from patients hospitalized with sepsis and mouse experiments to examine the interplay between the mix of bacteria in the gut, temperature fluctuations 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 the American Journal of Respiratory and Critical Care Medicine in 2019 has shown that hospitalized patients with sepsis vary widely in their temperature responses, and this variation predicts their survival.

“There’s a reason temperature is a vital sign,” says Kale Bongers MD Ph.D., a clinical instructor in the Department of Internal Medicine and lead author of the study. “It’s both easy to measure and tells us important information about the body’s inflammatory and metabolic state.”

Yet the causes of this temperature variation, both in sepsis and health, have remained 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 hospitalized patients. The gut microbiota of the patients varied widely, confirming that it is a potential source of variation.

“No doubt our patients have more variation in their microbiota than in their own genetics,” said Bongers. “Any two patients are more than 99% identical in their own genomes, while they may have literally 0% overlap in their gut bacteria.”

The authors found that this variation in gut bacteria was related to the patient’s temperature ranges in the hospital. In particular, common bacteria from the Firmicutes phylum were most strongly associated with an enhanced fever response. These bacteria are common, vary by patient, and are known to produce important metabolites that enter the bloodstream and affect the body’s immune response and metabolism.

This shows a diagram of the intestines
The gut microbiota of the patients 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 to genetically identical mice lacking a microbiome. Experimental sepsis caused dramatic changes in the temperature of conventional mice, but had a blunted effect on the temperature response of germ-free mice. In mice with a microbiome, variation in temperature response was highly correlated with the same family of bacteria (Lachnospiraceae) found in humans.

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

Even when healthy, mice lacking a 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 could explain the decrease 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,” says Bongers. “Human genetics have not changed substantially in the last 150 years, but changes in diet, hygiene and antibiotics have had profound effects on our gut bacteria.”

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

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About this neuroscience research news

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

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


Abstract

The gut microbiome modulates body temperature in both sepsis and health

Rationale: In patients with sepsis, variation in temperature ranges predicts clinical outcomes. In healthy individuals, normal body temperature is variable and has been constantly declining since the 1860s. The biological underpinnings of this temperature variation in disease and health are unknown.

Goals: To identify and investigate the role of the gut microbiome in calibrating body temperature.

methods: We performed a series of translational analyzes and experiments to determine if and how variation in the gut microbiota explains the variation in body temperature in sepsis and health. We studied patients’ temperature trajectories using electronic medical record data. 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 antibiotic, germ-free and gnotobiotic animals.

Measurements and main results: Consistent with previous work, we identified four temperature ranges in patients hospitalized with sepsis that predicted clinical outcomes. In a separate cohort of 116 hospitalized patients, we found that the gut microbiota composition of patients on admission predicted their temperature ranges. Germ-free mice had less temperature loss during experimental sepsis compared to conventional mice. In conventional mice, the heterogeneity of the temperature response in sepsis was strongly explained by variation in the gut microbiota. Healthy germ-free and antibiotic-treated mice both had lower basal body temperatures compared to controls. The Lachnospiraceae family was consistently associated with temperature ranges in hospitalized patients, experimental sepsis, and antibiotic-treated mice.

Conclusions: The gut microbiome is an important modulator of body temperature variation, both in health and critical illness, and thus represents an important, under-explored target for modulating physiological heterogeneity in sepsis.

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