Caloric restriction alleviates radiation injuries in a sex‐dependent fashion

Abstract

Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sexspecific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.

The gut microbiota as a booster for radiotherapy: novel insights into radio-protection and radiation injury

“…In their reports, circadian rhythm disturbances [ 7 ] and food additive polysorbate-80 [ 8 ] disturbing the gut microbiota lead to radiation injury deterioration. Whereas modified diets [ 9 , 10 ], anti-cholesterol agent simvastatin [ 9 ] and anti-oxidant molecules [ 11 – 14 ] mitigate radiation injury in a microbiota-dependent manner. Noteworthy, a series of gender-specific phenotypes in relation with gut microbiota interplaying with radiation injury is repeatedly reported in Fan’s animal models [ 5 , 9 , 10 ]whose underlying mechanism is unclear.…”

“…Whereas modified diets [ 9 , 10 ], anti-cholesterol agent simvastatin [ 9 ] and anti-oxidant molecules [ 11 – 14 ] mitigate radiation injury in a microbiota-dependent manner. Noteworthy, a series of gender-specific phenotypes in relation with gut microbiota interplaying with radiation injury is repeatedly reported in Fan’s animal models [ 5 , 9 , 10 ]whose underlying mechanism is unclear. Whether similar manifestations exist in human as a possible explanation for the sex differences in treatment efficacy and toxicity [ 15 ] remain to be investigated.…”

Radiation enteropathy‐related depression: A neglectable course of disease by gut bacterial dysbiosis

“…Another study by Li et al. found that 30% calorie‐restricted dietary preconditioning ameliorated radiation enterotoxicity, which was associated with a reduced abundance of pro‐inflammatory bacteria and increased numbers of short‐chain fatty acid‐producing bacteria 148 . Recently, Wang et al.…”

“…147 Another study by Li et al found that 30% calorie-restricted dietary preconditioning ameliorated radiation enterotoxicity, which was associated with a reduced abundance of pro-inflammatory bacteria and increased numbers of short-chain fatty acid-producing bacteria. 148 Recently, Wang et al found that orally administered carbon nanoparticles can remove ROS, prevent gut bacterial dysbiosis, and reduce the apoptosis of intestinal epithelial cells to play a role in radiation protection. 149…”

High-fat diet alters the radiation tolerance of female mice and the modulatory effect of melatonin

“…14 Furthermore, a calorie-restricted diet consumed for 10 days prior to radiation was found to sex-specifically modulate the structure of gut microbiota and protect mice from the side effects induced by IR. 42 However, the effects of an HFD on radiation-induced damage remains unclear.…”