High Throughput Sequencing Reveals Distinct Microbial Populations Within the Mucosal and Luminal Niches in Healthy Individuals

Overview

Journal Gut Microbes

Specialties Gastroenterology
Microbiology

Date 2015 Apr 28

PMID 25915459

Citations 115

Authors

Yehuda Ringel

Nitsan Maharshak

Tamar Ringel-Kulka

Elizabeth Ashley Wolber

R Balfour Sartor

Ian M Carroll

Affiliations

Soon will be listed here.

Abstract

Background: The intestinal microbiota is associated with human health and diseases. The luminal microbiota (LM) and the mucosal-associated microbiota (MAM) are 2 distinct ecosystems with different metabolic and immunological functions.

Aim: To characterize the intestinal LM and MAM in humans using high throughput sequencing of the 16S rRNA gene.

Methods: Fresh fecal samples and distal colonic mucosal biopsies collected from 24 healthy subjects before (fecal) and during (mucosa) a flexible sigmoidoscopy of an un-prepared bowel. High throughput sequencing of the 16S rRNA gene was used to characterize bacterial communities. Sequences were processed using the QIIME pipeline.

Results: LM and MAM populations were significantly different (ANOSIM: R = 0.49, P = 0.001). The LM displayed tighter clustering compared to the MAM (average weighted UniFrac distances 0.27 ± 0.05 vs. 0.43 ± 0.09, P < 0.001, respectively), and showed higher diversity (Shannon diversity index: 4.96 ± 0.37 vs 4.14 ± 0.56, respectively, P < 0.001). The dominant phyla in the LM and MAM were significantly different: Firmicutes (41.4% vs. 29.1%, FDR < 0.0001, respectively), Bacteroidetes (20.2% vs. 26.3%, FDR < 0.05, respectively), Actinobacteria (22% vs. 12.6%, FDR < 0.0001, respectively) and Proteobacteria (9.3% vs. 19.3%, FDR < 0.0001, respectively). The abundance of 56 genera differed significantly (FDR < 0.1) between the 2 niches. All of the genera in the fecal microbiota were present in the MAM while 10 genera were found to be unique to the MAM.

Conclusion: The LM and MAM are distinct microbial ecosystems that differ significantly from each other in microbial diversity and composition. These two microbial niches should be investigated independently to better understand the role of the intestinal microbiota in health and disease.

Citing Articles

MIIST305 mitigates gastrointestinal acute radiation syndrome injury and ameliorates radiation-induced gut microbiome dysbiosis.

Mitra D, Armijo G, Ober E, Baker S, Turner H, Broustas C Gut Microbes. 2025; 17(1):2458189.

PMID: 39930324 PMC: 11817531. DOI: 10.1080/19490976.2025.2458189.

Study of Microbiota Associated to Early Tumors Can Shed Light on Colon Carcinogenesis.

Aspesi A, La Vecchia M, Sala G, Ghelardi E, Dianzani I Int J Mol Sci. 2025; 25(24.

PMID: 39769073 PMC: 11677268. DOI: 10.3390/ijms252413308.

Comparison of mucosal microbiota populations across the gastrointestinal tract of healthy dogs.

Lin C, Cross T, Swanson K Anim Microbiome. 2025; 7(1):2.

PMID: 39762940 PMC: 11702091. DOI: 10.1186/s42523-024-00368-7.

Effect of Chemotherapy on Abundance in Colorectal Cancer Patients: A Study on Relapsing Patients.

Zuraik A, Daboul Y, Awama M, Yazigi H, Kayasseh M, Georges M Indian J Microbiol. 2024; 64(4):1938-1950.

PMID: 39678992 PMC: 11645352. DOI: 10.1007/s12088-024-01279-6.

Antibiotic-perturbed microbiota and the role of probiotics.

Szajewska H, Scott K, de Meij T, Forslund-Startceva S, Knight R, Koren O Nat Rev Gastroenterol Hepatol. 2024; 22(3):155-172.

PMID: 39663462 DOI: 10.1038/s41575-024-01023-x.

References

Araujo-Perez F, Mccoy A, Okechukwu C, Carroll I, Smith K, Jeremiah K . Differences in microbial signatures between rectal mucosal biopsies and rectal swabs. Gut Microbes. 2012; 3(6):530-5. PMC: 3495790. DOI: 10.4161/gmic.22157. View

Momozawa Y, Deffontaine V, Louis E, Medrano J . Characterization of bacteria in biopsies of colon and stools by high throughput sequencing of the V2 region of bacterial 16S rRNA gene in human. PLoS One. 2011; 6(2):e16952. PMC: 3037395. DOI: 10.1371/journal.pone.0016952. View

Parkes G, Rayment N, Hudspith B, Petrovska L, Lomer M, Brostoff J . Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome. Neurogastroenterol Motil. 2011; 24(1):31-9. DOI: 10.1111/j.1365-2982.2011.01803.x. View

Carroll I, Ringel-Kulka T, Siddle J, Ringel Y . Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012; 24(6):521-30, e248. PMC: 3975596. DOI: 10.1111/j.1365-2982.2012.01891.x. View

Lozupone C, Lladser M, Knights D, Stombaugh J, Knight R . UniFrac: an effective distance metric for microbial community comparison. ISME J. 2010; 5(2):169-72. PMC: 3105689. DOI: 10.1038/ismej.2010.133. View

Kamada N, Seo S, Chen G, Nunez G . Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013; 13(5):321-35. DOI: 10.1038/nri3430. View

Sokol H, Lepage P, Seksik P, Dore J, Marteau P . Molecular comparison of dominant microbiota associated with injured versus healthy mucosa in ulcerative colitis. Gut. 2006; 56(1):152-4. PMC: 1856643. DOI: 10.1136/gut.2006.109686. View

Lyra A, Forssten S, Rolny P, Wettergren Y, Lahtinen S, Salli K . Comparison of bacterial quantities in left and right colon biopsies and faeces. World J Gastroenterol. 2012; 18(32):4404-11. PMC: 3436058. DOI: 10.3748/wjg.v18.i32.4404. View

Preheim S, Perrotta A, Friedman J, Smilie C, Brito I, Smith M . Computational methods for high-throughput comparative analyses of natural microbial communities. Methods Enzymol. 2013; 531:353-70. DOI: 10.1016/B978-0-12-407863-5.00018-6. View

10.

Backhed F, Fraser C, Ringel Y, Sanders M, Sartor R, Sherman P . Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe. 2012; 12(5):611-22. DOI: 10.1016/j.chom.2012.10.012. View

11.

Kim Y, Ho S . Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep. 2010; 12(5):319-30. PMC: 2933006. DOI: 10.1007/s11894-010-0131-2. View

12.

Walker A, Sanderson J, Churcher C, Parkes G, Hudspith B, Rayment N . High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol. 2011; 11:7. PMC: 3032643. DOI: 10.1186/1471-2180-11-7. View

13.

Swidsinski A, Loening-Baucke V, Verstraelen H, Osowska S, Doerffel Y . Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology. 2008; 135(2):568-79. DOI: 10.1053/j.gastro.2008.04.017. View

14.

Albenberg L, Esipova T, Judge C, Bittinger K, Chen J, Laughlin A . Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology. 2014; 147(5):1055-63.e8. PMC: 4252572. DOI: 10.1053/j.gastro.2014.07.020. View

15.

Ringel Y, Maharshak N . Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2013; 305(8):G529-41. PMC: 3798736. DOI: 10.1152/ajpgi.00207.2012. View

16.

Arthur J, Gharaibeh R, Uronis J, Perez-Chanona E, Sha W, Tomkovich S . VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sci Rep. 2013; 3:2868. PMC: 3792409. DOI: 10.1038/srep02868. View

17.

Caporaso J, Kuczynski J, Stombaugh J, Bittinger K, Bushman F, Costello E . QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010; 7(5):335-6. PMC: 3156573. DOI: 10.1038/nmeth.f.303. View

18.

Carroll I, Ringel-Kulka T, Siddle J, Klaenhammer T, Ringel Y . Characterization of the fecal microbiota using high-throughput sequencing reveals a stable microbial community during storage. PLoS One. 2012; 7(10):e46953. PMC: 3465312. DOI: 10.1371/journal.pone.0046953. View

19.

Carroll I, Ringel-Kulka T, Keku T, Chang Y, Packey C, Sartor R . Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2011; 301(5):G799-807. PMC: 3220325. DOI: 10.1152/ajpgi.00154.2011. View

20.

Eckburg P, Bik E, Bernstein C, Purdom E, Dethlefsen L, Sargent M . Diversity of the human intestinal microbial flora. Science. 2005; 308(5728):1635-8. PMC: 1395357. DOI: 10.1126/science.1110591. View