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Professor Ana Domingos and DPhil student Conan O’Brien review a new study demonstrating that fasting and re-feeding causes monocytes to re-enter the bone marrow and alter the body's response to infection.

© Dr Graham Beards
Micrograph of Giemsa-stained monocytes

Fasting is generally considered to be beneficial for the human body, provided it does not lead to starvation. Researchers have observed that fasting can improve immunity and inflammatory responses by reducing the levels of inflammatory immune cells circulating in the blood stream. It has also been shown to impact nutrient signalling pathways and ‘slow down’ ageing, demonstrating that it can promote a longer life and health span. However, the mechanisms underpinning these effects have not yet been fully explored. Particularly in the context of immunity and inflammation, the majority of studies have focused solely on the effects of fasting, but not the effects of fasting followed by re-feeding and the subsequent effects on inflammation. Consequently, our understanding of these processes remains incomplete.

Professor Ana Domingos and DPhil student Conan O’Brien have reviewed a recent piece of innovative new research that sought to reveal the full fate of the inflammatory immune cells following fasting. In this study from Janssen and colleagues, their findings showed that monocytes – the precursors of macrophages – re-enter the bone marrow and in fact become more inflammatory or ‘hangry’ during fasting. The research team then observed the effects of fasting when the body has a bacterial infection. To do so they introduced pseudomonas aeruginosa, an opportunistic pathogen that can cause pneumonia and blood infections in the immunocompromised. The team observed enhanced systemic inflammation, more inflammatory macrophages, and reduced survival. As a result, the study shows that fasting and re-feeding can in fact be maladaptive and harmful in the context of infection.

Having reviewed these results, Conan O’Brien said: “It is surprising that, in this inflammatory context, fasting appears to be harmful, given that it has been shown to be mostly beneficial in other contexts. Moreover, immune cells such as monocytes usually move in a uni-directional manner from bone marrow to blood to tissue. Here they show that upon fasting, monocytes return to the bone marrow, only to burst out again upon re-feeding, more inflammatory than before.

“Given the rising prevalence of fasting for the perceived health benefits, and importance of monocytes and macrophages in mediating immunity and a wide variety of physiological processes, this study warrants further investigations into the effects of fasting on bodily function.

“These findings may suggest that fasting should be avoided by people whose immune systems are compromised, should it increase susceptibility to infection in humans in the same way as shown in this study.”

The full review ‘Old and “hangry” monocytes turn from friend to foe under assault’ is published in Immunity.