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Caenorhabditis elegans as a Convenient Animal Model for Microbiome Studies

Microbes constitute the most prevalent life form on Earth, yet their remarkable diversity remains mostly unrecognized. Microbial diversity in vertebrate models presents a significant challenge for investigating host–microbiome interactions. The model organism Caenorhabditis elegans has many advantages for delineating the effects of host genetics on microbial composition. In the wild, the C. elegans gut contains various microbial species, while in the laboratory it is usually a host for a single bacterial species. There is a potential host–microbe interaction between microbial metabolites, drugs, and C. elegans phenotypes. This mini-review aims to summarize the current understanding regarding the #microbiome in C. elegans. Examples using C. elegans to study host–microbe–metabolite interactions are discussed.

1. Introduction

1.1. C. elegans as a Model Organism

Caenorhabditis elegans is a free-living nematode found worldwide in diverse environments, and it usually hosts a microbial community similar to that found in the surrounding environment. The wild-type strain of C. elegans—often known as “soil nematode”, Sydney Brenner’s C. elegans, or the iconic N2 strain—was isolated from decomposed mushrooms in Bristol, United Kingdom [1]. C. elegans, although usually mistaken for a soil nematode, can readily be isolated from rotting vegetables or human-made compost heaps, which have an abundant pool of the nematode’s bacterial nutrition source.

A four-year survey of French orchards by Félix and Duveauin showed the presence of flourishing populations of C. elegans in decomposing fruits and plants [2]. C. elegans is found in rotting fruits of many kinds, as well as in the rotting stems of herbaceous plants. It is often found with C. briggsae. Both species can be found in the same fruit (20% of decaying apples from Orsay, France), and exhibit reproducible seasonal shifts in abundance. Rotting fruits and stems frequently incorporate hundreds of worms and all their life phases, including a rare type of male.

In its natural habitat, the C. elegans microbiota includes a gut microbial community and possibly microbes physically associated with its surface. C. elegans interacts with a wide range of microorganisms, comprising bacteria, fungi, and other microbes. Various factors, including soil type, geographic location, and environmental conditions, influence the composition of its microbiome [3]. As a result, the microbiome of C. elegans may exhibit considerable variation.

1.2. Advantages in Biomedical and Microbiome Studies

Symbiotic microbes develop different relationships with their host. Mammalian microorganisms mainly display mutualism in evolution. Disruptions in the balance of the host–microbiome relationship, referred to as dysbiosis, can alter the growth, fitness, and metabolism of the host [4]. This can result in development of various diseases [5]. With an enhanced appreciation of their contributions to host pathophysiology, the exploration of the human microbiota has garnered much attention in recent years [6]. A complete understanding of the complex host–microbiome interactions is essential for developing effective microbial therapeutics. However, it can be challenging to investigate host–microbiome interactions in vertebrate models, as the relationship between an individual member of the mammalian microbiome and the host is influenced by variable factors, such as host genetics, the environment, and heterogeneity of the mammalian immune system.

Studies with other commonly used animals, such as murine models, are limited by the cost and restrictions of high-throughput analysis. The genome of C. elegans has been fully sequenced and annotated, and nematodes are highly amenable to genetic manipulations through traditional forward/reverse genetic screening and novel genome-editing technology, such as CRISPR [7]. This organism’s short lifespan is also useful for studying biological phenomena such as longevity.

The life cycle of C. elegans consists of an initial embryonic stage followed by four distinctive larval stages (L1–L4), which culminate in the adult stage (Figure 1). The N2 strain of C. elegans completes one generation every 3.5 days at 20 °C. This organism may enter a long-term survival stage, referred to as dauer (which means “duration” in German), as an alternative to the standard L3 larval stage (Figure 1). The distinct developmental stages allow for the study of embryogenesis, development, and dauer formation. The life cycle also allows for the establishment of large-scale cultures for high-throughput study. The transparency of the C. elegans body allows direct observations of anatomical structures and fluorescently tagged molecules of interest. Additionally, the nematodes can be easily cryopreserved, and many strains are available from the Caenorhabditis Genetics Center “ (accessed on 14 June 2024)”. These attributes make C. elegans a widely accepted model organism for biomedical research.

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