Gut microbiome recovery after the destructive effect of antibiotics depends on 'keystone' species of bacteria such as Bacteroides thetaiotaomicron.

© A*STAR’s Genome Institute of Singapore (GIS)

Unraveling the gut microbial food web

24 Feb 2021

Keystone bacterial species help to restore gut microbial diversity after treatment with antibiotics, paving the way for improved prebiotic and probiotic formulations.

Like coral reefs and tropical rainforests, our bodies consist of intricate ecosystems that keep us healthy. Typically, these ecosystems are inhabited by diverse communities of microbes, which are often referred to as microbiomes. Within these microbiomes, the micro-organisms are more likely to be organized into a food web, where a few keystone species are essential for the survival of many others.

Disruptions to these ecosystems, such as from antibiotic treatment, are a major cause of long-term changes to the community of microbes.

To understand how the gut recovers from microbiome perturbations, study co-corresponding author Niranjan Nagarajan, a Senior Group Leader at A*STAR’s Genome Institute of Singapore (GIS), and colleagues sought to identify the species of bacteria responsible for the recovery of the full diversity of microbial flora after antibiotic treatment.

Using metagenomics—a technique that analyzes the profiles of micro-organisms within an environment—the researchers studied four cohorts of patients from Singapore, Canada, England and Sweden, each one given different classes of antibiotics.

“The patients were classified into ‘recoverers’ and ‘non-recoverers’ based on the abilities of their gut microbiomes to return to high diversities after antibiotics treatment,” said Nagarajan.

Recoverers exhibited a ‘U-shaped’ diversity profile where their gut microbiome diversities rebounded after antibiotics treatment, while non-recoverers continued to have low gut microbiome diversities within the same period.

In total, 21 microbial species were identified to be significantly associated with microbiome recovery in at least two of the four cohorts. The research team called these recovery-associated bacterial species or RABs.

Looking deeper, the researchers found that the gut microbiome in recovered patients was enriched for genes associated with carbohydrate-degradation and energy-metabolism pathways. Specifically, carbohydrate-active enzyme families of genes—or CAZymes—were more abundant in RABs than other microbial species.

The researchers next used a computational method to look at where RABs fit into the gut microbial food web. They found that many of the 21 RABs were primary species—keystone species that are essential for repopulating the community, such as Bacteroides thetaiotaomicron—while others were tertiary species that play a more synergistic role, such as Bifidobacterium adolescentis.

Using mice studies, the team also showed that the primary and the tertiary RABs synergistically provided a 100-fold boost to absolute microbial abundance. Further, this group also exhibited a higher diversity in the gut microbiome after antibiotic treatment compared to the controls that were administered with either a tertiary species or a control substance.

“We are working on follow-up projects that aim to further characterize the mechanisms and synergies involved in gut microbiome recovery,” said Nagarajan. “In time, we hope to promote gut microbiome recovery through the consumption of appropriate prebiotics and probiotics.”

The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore (GIS).

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Chng, K.R., Ghosh, T.S., Tan, Y.H., Nandi, T., Lee, I.R., et al. Metagenome-wide association analysis identifies microbial determinants of post-antibiotic ecological recovery in the gut. Nature Ecology & Evolution 4, 1256–1267 (2020) | article

About the Researcher

Niranjan Nagarajan

Associate Director

Genome Institute of Singapore
Niranjan Nagarajan is an Associate Director and a Senior Group Leader at A*STAR's Genome Institute of Singapore (GIS), and an Associate Professor at the Department of Medicine and Department of Computer Science at the National University of Singapore. His research focuses on developing cutting edge genome analytic tools and using them to study the role of microbial communities in human health. Nagarajan received a BA degree in Computer Science and Mathematics from Ohio Wesleyan University in 2000, and a PhD degree in Computer Science from Cornell University in 2006. He carried out his postdoctoral research in the Center for Bioinformatics and Computational Biology at the University of Maryland, working on problems in genome assembly and metagenomics.

This article was made for A*STAR Research by Wildtype Media Group