SCI 발표논문

SCI 발표논문

← SCI 발표논문 목록

J Neurogastroenterol Motil. 2021;27(1):134-146.

Changes in Cecal Microbiota and Short-chain Fatty Acid During Lifespan of the Rat.

, , , , , , , , , , , ,

제1저자 최수인, 손주희 · 교신저자 김나영

PMID 33380558 PMC7786083 DOI 10.5056/jnm20148 IF 3.7 소화기내과
소속 (5)
  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
  2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  3. Digestive Disease Research Institute and DCNbio research center, Wonkwang University, Iksan, Jeollabuk-do, Korea.
  4. Department of Internal Medicine, Wonkwang University Sanbon Medical Center, Gunpo-si, Gyeonggi-do, Korea.
  5. Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Korea.

Abstract

BACKGROUND/AIMS The gut microbiota regulates intestinal immune homeostasis through host-microbiota interactions. Multiple factors affect the gut microbiota, including age, sex, diet, and use of drugs. In addition, information on gut microbiota differs depending on the samples. The aim of this study is to investigate whether changes in cecal microbiota depend on aging.

METHODS Gut microbiota in cecal contents of 6-, 31-, and 74-week-old and 2-year-old male Fischer-344 rats (corresponding to 5-, 30-, 60-, and 80-year-old humans in terms of age) were analyzed using 16S ribosomal RNA metagenome sequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) based on the Kyoto Encyclopedia of Genes and Genomes orthology. Moreover, short-chain fatty acid (SCFA) level in cecum and inflammation related factors were measured using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay.

RESULTS Alpha and beta diversity did not change significantly with age. At the family level, Lachnospiraceae and Ruminococcaceae, which produce SCFAs, showed significant change in 31-week-old rats: Lachnospiraceae significantly increased at 31 weeks of age, compared to other age groups, while Ruminococcaceae decreased. Butyrate levels in cecum were significantly increased in 31-week-old rats, and the expression of inflammation related genes was increased followed aging. Especially, EU622775_s and EU622773_s, which were highly abundance species in 31-week-old rats, showed significant relationship with butyrate concentration. Enzymes required for producing butyrate-acetyl-CoA transferase, butyryl-CoA dehydrogenase, and butyrate kinase-were not predicted by PICRUSt.

CONCLUSIONS Major bacterial taxa in the cecal lumen, such as Lachnospiraceae, well-known SCFAs-producing family, changed in 31-week-old rats. Moreover, unknown species EU622775_s and EU622773_s showed strong association with cecal butyrate level at 31 weeks of age.

Keywords

AgingButyrateCecumMicrobiotaRats

Figures

Figure 1
Figure 1 Beta and alpha diversity of cecal microbiota of 6-week-old (6 wk), 31-week-old (31 wk), 74-week-old (74 wk), and 2-year-old (2 yr) rats. (A) Principal coordinates analysis (PCoA) of cecal microbiota depending on the age of the rats. x-axis: 1st PC, percent variation explained 14.951%; y-axis: 2nd PC, percent variation explained 9.904%. (B-D) Comparison of the alpha diversity index of the cecal microbiota at different ages; (B) the observed operational taxonomic unit (OTU) count, (C) Chao 1, and (D) Shannon index. NS, not significant.
Figure 2
Figure 2 The compositional characteristics of cecal microbiota vary with age at the (A) phylum level, and at the (B-G) family level. **P < 0.01 from Mann-Whitney U test with Holm-Bonferroni correction as post hoc analysis followed by Kruskal-Wallis test. 6 wk, 6-week-old; 31 wk, 31-week-old; 74 wk, 74-week-old; 2 yr, 2-year-old.
Figure 3
Figure 3 Linear discriminant analysis effect size (LEfSe) analysis results comparing 2 age groups (A-F). (G) The ratio of commensal to opportunistic pathogens calculated from LEfSe results. The 6- and 31-week-old groups showed a higher ratio steadily than the other age groups. 6 wk, 6-week-old; 31 wk, 31-week-old; 74 wk, 74-week-old; 2 yr, 2-year-old. LDA, linear discriminant analysis; NC, not characterized.
Figure 4
Figure 4 Enterotypes in the cecal microbiota. (A) Principal coordinates analysis (PCoA) separated the 2 enterotypes. (B) Dominant bacteria and their abundance in each enterotype at family level. In enterotype 2 (E2), EU622775_s (C), and EU622773_s (D) showed a significant difference compared to enterotype 1 (E1) but there was no difference in the case of Akkermansia muciniphila (E). **P < 0.01, ***P < 0.001 from Mann-Whitney U test. 6 wk, 6-week-old; 31 wk, 31-week-old; 74 wk, 74-week-old; 2 yr, 2-year-old. NS, not significant.
Figure 5
Figure 5 Cecum luminal butyrate concentration (A), IL-6 (B), and gene related with inflammation transcriptional expression such as cyclooxygenase-2 (COX-2) (C), inducible nitric oxide synthase (iNOS) (D), TNF-α (E), and claudin-2 (F) were compared. *P < 0.05, ***P < 0.001 from Mann-Whitney U test with Holm-Bonferroni correction as post hoc analysis followed by Kruskal-Wallis test. 6 wk, 6-week-old; 31 wk, 31-week-old; 74 wk, 74-week-old; 2 yr, 2-year-old.
Figure 6
Figure 6 The correlation analysis between luminal butyrate concentration and compositional change of microbiota in cecum. (A) Lachnospiraceae, (B-C) EU622775_s, and (D-E) EU622773_s. **P < 0.01 from Mann-Whitney U test with Holm-Bonferroni correction as post hoc analysis followed by Kruskal-Wallis test. Dotted line indicates linear regression. 6 wk, 6-week-old; 31 wk, 31-week-old; 74 wk, 74-week-old; 2 yr, 2-year-old.
Figure 7
Figure 7 Relative abundance of known butyrate-producing bacteria based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and NCBI BLASTp, above a score of 1200 and 50% identity. (A) Oscillibacter species, (B) Intestinimonas butyriciproducens, (C) Kineothrix alysoides, (D) Flintibacter butyricus group, and (E) Pseudoflavonifractor_uc. *P < 0.05 from Mann-Whitney U test with Holm-Bonferroni correction as post hoc analysis followed by Kruskal-Wallis test. 6 wk, 6-week-old; 31 wk, 31-week-old; 74 wk, 74-week-old; 2 yr, 2-year-old.

그림 출처: PubMed Central 공개 논문 (PMC7786083)

Conflict of interest statement

Conflicts of interest: None.

그 밖의 정보
출판 형태
Journal Article
저널
Journal of neurogastroenterology and motility · ISSN 2093-0879
참고문헌
38편