Smell prepares nematodes and the human gut to combat infections

Many organisms instinctively avoid the smell of deadly pathogens, but a recent study by the University of California, Berkeley, reveals that the nematode C. elegans not only detects the odor of pathogenic bacteria but also prepares its intestinal cells to defend against a potential infection. So Smell prepares nematodes and the human gut to combat infections, the research was published on June 21 in the journal Science Advances.

Date	August 7, 2024
Source	University of California – Berkeley
Summary	In both nematodes and humans, mitochondrial stress in the nervous system triggers a body-wide response, particularly affecting the gut.

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A recent study revealed that in nematodes, the odor of a pathogen activates the nervous system to signal this response throughout the organism, preparing intestinal cell mitochondria to combat bacterial infection. Humans might also be able to detect pathogenic smells that prime the gut for an infection.

Just see what is C. elegans?

• Like humans, nematodes often face gut infections from harmful bacteria. In response, C. elegans destroys iron-containing organelles called mitochondria, which are responsible for producing cellular energy, to protect iron from bacteria that steal it. Iron is crucial for many enzymatic reactions, especially in generating ATP, the cell’s energy currency.
• The discovery of this protective response in nematodes suggests that other organisms, including mammals, may also have the ability to respond defensively to the scent of pathogens, according to Andrew Dillin, a UC Berkeley professor of molecular and cell biology and a Howard Hughes Medical Institute (HHMI) investigator.
• So far, this response has only been observed in C. elegans. Still, the discovery is surprising, given that the nematode is one of the most extensively studied organisms in labs, where biologists have tracked every cell from embryo to death.
• There’s evidence suggesting that beyond this mitochondrial response, a more generalized immune response might be triggered just by smelling bacterial odors. Since olfaction plays a significant role in regulating physiology and metabolism across animals, it’s entirely possible that mammals also have a similar mechanism to C. elegans.

How do Smell prepares nematodes and the human gut to combat infections?

• Stress in the nervous system activates protective cellular responses, particularly through a suite of genes that stabilize proteins in the endoplasmic reticulum, a process known as the unfolded protein response (UPR). This UPR serves as a “first aid kit” for mitochondria, which are not only the cell’s powerhouses but also play essential roles in signaling, cell death, and growth.
• The errors in the UPR network can lead to disease and aging and that mitochondrial stress in one cell can communicate with mitochondria across the body. What environmental factors trigger the nervous system to signal this stress?
• Our nervous system evolved to detect environmental cues and maintain homeostasis throughout the organism. The smell neurons detect these cues and identified the specific odorants from pathogens that activate this response.
• Mitochondria’s sensitivity to the smell of pathogenic bacteria might be a vestige from when mitochondria were free-living bacteria before becoming the power plants of eukaryotic cells about 2 billion years ago. These eukaryotes eventually evolved into multicellular organisms with specialized organs, like animals and humans.
• The smell of pathogens triggers an inhibitory response, sending a signal throughout the body. This was evident when he ablated olfactory neurons in the worm, causing all peripheral cells, particularly intestinal cells, to exhibit the stress response typical of threatened mitochondria. The study also identified serotonin as a key neurotransmitter communicating this information body-wide.
• Now mapping the neural circuits from smell neurons to peripheral cells and investigating the neurotransmitters involved. Researchers are also exploring whether a similar response occurs in mice in relation toSmell prepares nematodes and the human gut to combat infections.

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