Stability in fecal metabolites amid a diverse gut microbiome composition: a one-month longitudinal study of variability in healthy individuals

Gut Microbes. 2024 Jan-Dec;16(1):2427878. doi: 10.1080/19490976.2024.2427878. Epub 2024 Nov 12.

Abstract

An extensive network of microbial-host interactions exists in the gut, making the gut microbiome a complex ecosystem to untangle. The microbial composition and the fecal metabolites are important readouts to investigate intricate microbiota-diet-host interplay. However, this ecosystem is dynamic, and it is of interest to understand the degree and timescale of changes occurring in the gut microbiota, during disease as well as in healthy individuals. Cross-sectional study design is often used to investigate the microbiome, but this design provides a static snapshot and cannot provide evidence on the dynamic nature of the gut microbiome. Longitudinal studies are better suited to extrapolate causation in a study or assess changes over time. This study investigates longitudinal change in the gut microbiome and fecal metabolites in 14 healthy individuals with weekly sampling over a period of one-month (four time points), to elucidate the temporal changes occurring in the gut microbiome composition and fecal metabolites. Utilizing 16S rRNA amplicon sequencing for microbiome analysis and NMR spectroscopy for fecal metabolite characterization, we assessed the stability of these two types of measurable parameters in fecal samples during the period of one month. Our results show that the gut microbiome display large variations between healthy individuals, but relatively lower within-individual variations, which makes it possible to uniquely identify individuals. The fecal metabolites showed higher stability over time compared to the microbiome and exhibited consistently smaller variations both within and between individuals. This relative higher stability of the fecal metabolites suggests a balanced, consistent output even amid individual's differences in microbial composition and they can provide a viable complementary readout to better understand the microbiome activity.

Keywords: 16S rRNA; NMR; fecal metabolites; gut microbiome; longitudinal study; multi-omics.

MeSH terms

  • Adult
  • Bacteria* / classification
  • Bacteria* / genetics
  • Bacteria* / isolation & purification
  • Bacteria* / metabolism
  • Cross-Sectional Studies
  • Feces* / chemistry
  • Feces* / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Healthy Volunteers*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • RNA, Ribosomal, 16S* / genetics
  • Young Adult

Substances

  • RNA, Ribosomal, 16S

Grants and funding

The study was supported by grants from the Swiss National Science Foundation (SNSF) (MS, Postdoc.Mobility-Stipendium; [grant number P400PM_194492]), Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU) [MS, grant 2023-34191], Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU (FFU) [GFG, grant 28328] and the Norwegian Cancer Society (Kreftforeningen) [GFG, grant 202021-2019]. JVL was funded by Medical Research Council New Investigator Grant [MR/P002536/1] and ERC Starting Grant [715662].