Lifelong Exposure to Caloric Restriction Restores the Microbiota of Aging Mice
Authors: Dursun Ali , Tuna Bilge , Keles Nazim , Dogan Soner , Sudagidan Mert , Cetiner Ozlem , Balci Tugce , Kavruk Murat , Ozalp Veli 
Published: May 2023

Gut microbiota regulates immunological response, oxidative stress, and intestinal cell cycle. Aging, poor diets, and sedentary lifestyles may change microbiota composition, causing obesity, diabetes, and many forms of cancer, including colorectal cancer. Caloric restriction (CR) increases healthy longevity, although its long-term implications are not well known. This research examines the effects of chronic and intermittent CR on colonic health and their potential benefits.10 weeks old female C57BL/6 mice were enrolled into three dietary groups: ad libitum (AL), chronic caloric restriction (CCR), and intermittent caloric restriction (ICR)(n=20 in each group). CCR group was applied to 15 % of restriction compared to AL group, while mice in ICR groups were applied to 60 % of restriction for one week (ICR-R) followed by AL diet for three weeks (ICR-RF) in a cyclic manner starting at 10 weeks of age until 81/82 weeks. The stool samples from caecum were collected at four different time points: week 10 (baseline), week 17/18, week 49/50, and week 81/82 (each week, n=5). The samples were homogenized in buffer solution. The microbiota composition was examined using 16S rRNA amplicon sequencing and metagenomic analysis. Total DNA was extracted and bacterial 16S rRNA V3-V4 gene regions were amplified. The sequencing was carried out using the iSEQ100 system (Illumina) pair-end read type and two reads of 151 bp read length. The sequencing data were analyzed by 16S Metagenomic software to determine the taxonomic distribution of bacterial communities from the kingdom to the species level.Barnesiella, Clostridium, and Eisenbergiella were the most prevalent genera across all diet types. In the AL group, Clostridium species grew by 14% from week 10 to week 82 in caecum stool samples. In the CCR group, the 12% increase in Clostridium species at week 50 of mouse age relative to baseline group was recovered by week 80. Eisenbergiella species in the ICR-R group declined by 14% in week 80 compared to baseline levels, but Clostridium species remained unchanged. In the ICR-RF group, Barnesiella species rose by about 17% between weeks 10 and 17, but returned to baseline by week 80. In addition, Eisenbergiella species declined by about 9 percent in week 17 of the ICR-RF group, but afterwards returned to baseline. Eisenbergiella species reduced across diet groups in all groups except the ICR-RF group. The relative abundance of Barnesiella species rose in the AL and CCR groups, whereas it was maintained in the ICR-RF and reduced in the ICR-R group. When comparing all groups, the rise in the amount of Clostridium species was only detected in the older AL groups.The present study proves that CR, particularly ICR, is very efficient in maintaining or restoring a healthy microbiome composition against age-related alterations. In addition, the current research reveals that changes in microbiota profile in the cancer-preventive effects of CR depend on the type of caloric intake. Atilim University Research Funds; ATU-BAD-2122-03 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.