Segmented filamentous bacteria and their occurrence in animal vendor facilities

by Laura Griffin, PhD | Published: October 10th, 2024

 

Key TakeawaysKey Takeaways

  • Segmented filamentous bacteria (SFB) play a crucial role in host immune system maturation, particularly in activating Th17 cells, which are important for gut barrier function and immune regulation. Their presence influences inflammatory disease progression in rodents, such as exacerbating colitis in specific models.
  • Initial studies suggested that SFB was vendor-specific, however, later research revealed that SFB presence varies within vendor facilities and changes over time, prompting researchers to avoid assumptions based on vendor alone.
  • Taconic Biosciences no longer routinely tests for SFB due to low demand but offers specialized testing on request. For microbiome studies requiring consistent bacterial presence, customized colonies or specialized services like Taconic’s TruBIOME® are recommended.

 

Segmented filamentous bacteria (SFB) were discovered in the mid-1960s in the ileums of mice and rats. These gram-positive, anaerobic, spore-forming commensals have since been identified in many vertebrate and invertebrate animal species, as well as in humans1. Despite occurrence in multiple species, SFB demonstrates host-specificity, meaning the cross-species colonization even between mice and rats does not occur2. With respect to rodents, longitudinal studies of juvenile mice have indicated that SFB appears around 20 days of age and rapidly becomes one of the dominant genera in the murine gut. Their status is transient, however, and SFB recede significantly as mice mature to adulthood3

SFB are unique in that they do not invade epithelial cells, penetrate the epithelial barrier, or induce inflammation; rather they possess unique characteristics that allow them to adhere to the ileal mucosa. They lack amino acid biosynthesis enzymes and adherence to the mucosa allows the bacteria to obtain essential nutrients from the host2. This interaction concurrently influences host immune system development, as SFB resides in close proximity to Peyer’s patches where naïve T cells undergo activation and expansion to helper T cells1,4. The most recognized immunomodulatory capability of SFB relates to its ability to drive maturation of IL-17-producing CD4+ T cells (Th17 cells), which possess antimicrobial and anti-inflammatory effects, while also playing a role in gut barrier function. SFB have also demonstrated an influence on IgA production and innate lymphoid cell-mediated barrier protection2. As such, it has been shown in rodents that the presence of SFB may influence inflammatory disease progression; for example, the presence of SFB in the gut of scid mice has been reported to exacerbate the colitis phenotype in a T cell transfer model of inflammatory bowel disease3.

SFB Abundance Across Animal Vendors

Following the discovery of the association of SFB with immune system maturation, several research units began to investigate Th17 abundance in relation to SFB across animal vendors. In a hallmark study by Ivanov et al.5, it was noted that C57BL/6J mice from the Jackson Laboratory had very low abundance of Th17 cells compared to C57BL/6NTac mice from Taconic Biosciences. Moreover, microbial transfer of cecal contents from conventional Taconic C57BL/6NTac mice into germ-free counterparts, also from Taconic, induced Th17 accumulation. Th17 accumulation was not observed when this procedure was replicated using conventional and germ-free C57BL/6 mice from the Jackson Laboratory. Cohabitation of the conventional Jackson and Taconic mice also induced Th17 accumulation in the Jackson mice.

Based on the data presented by Ivanov et al. in 2009, the preclinical research community broadly concluded that all mice from the Jackson Laboratory are devoid of SFB and all conventional Taconic mice have SFB. This finding resonated particularly with researchers concerned with the effect of SFB-supported Th17 cell maturation and potential downstream effects related to host immunity. The preclinical research community saw a marked change in animal purchasing behavior, particularly among microbiome research units, with researchers ordering animals from specific vendors based on the supposed presence or absence of SFB.

This behavior has persisted for over a decade, based on a simplistic interpretation of these research results, which were representative of specific vendor colonies at a specific time, rather than more broadly representative of all stock at a particular vendor. In fact, in 2015 the Ivanov group reported finding SFB present in some animals from both vendors. In this particular study, the researchers divulged that they screen all incoming animal cohorts for SFB and have found SFB to be present in some cohorts from the Jackson Laboratory as well as from Taconic.  Moreover, they stated that the abundance of this bacteria is barrier-specific; thus cohorts of mice from certain locations at Jackson may contain SFB whilst cohorts from Taconic may not4

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With this revised statement in mind, if SFB status is important for a particular research study, animals should not be selected based on assumed SFB status. Do not assume that all barriers within a vendor facility are SFB positive or negative, nor that SFB status in a location is static over time. It may be beneficial to routinely monitor SFB status upon receipt of animal cohorts if this is a critical factor for your studies.

SFB Reporting and Restriction at Taconic

There are several Taconic health standards available to choose from when purchasing animals, from conventional through germ-free. Taconic previously tested for and reported SFB on all health reports, and the Taconic Excluded Flora (EF) health standard excluded SFB for the benefit of microbiome researchers. Taconic ceased routine SFB testing and reporting in 2022 due to insufficient market demand, and the Excluded Flora health standard was retired. This aligned Taconic with other major rodent vendors, none of which treated SFB as an organism on which to report or exclude. Taconic does not currently offer any conventional animals with guaranteed SFB presence or exclusion but can provide limited SFB testing for orders upon request. Germ-free mice, several strains of which are available from Taconic, lack SFB along with other gut bacteria and micro-organisms, but these represent special-purpose animals which are not recommended for routine studies.

Options for Microbiome Studies

For studies in which presence and consistency of a particular microbiome over time is critical, standard vendor animals may not be sufficient. Separate colonies of microbiome-controlled animals can be generated from axenic starting stock and maintained via specialized husbandry. Taconic offers the TruBIOME® service to address this need.


References:

  1. Oemcke LA, Anderson RC, Altermann E, Roy NC, McNabb WC. The Role of Segmented Filamentous Bacteria in Immune Barrier Maturation of the Small Intestine at Weaning. Front Nutr. 2021;8:759137. doi:10.3389/fnut.2021.759137
  2. Flannigan KL, Denning TL. Segmented filamentous bacteria‐induced immune responses: a balancing act between host protection and autoimmunity. Immunology. 2018;154(4):537-546. doi:10.1111/imm.12950
  3. Ericsson AC, Hagan CE, Davis DJ, Franklin CL. Segmented filamentous bacteria: commensal microbes with potential effects on research. Comp Med. 2014;64(2):90-98.
  4. Farkas AM, Panea C, Goto Y, Nakato G, Galan-Diez M, Narushima S, et al. Induction of Th17 cells by segmented filamentous bacteria in the murine intestine. J Immunol Methods. 2015;421:104-111. doi:10.1016/j.jim.2015.03.020
  5. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, et al. Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria. Cell. 2009;139(3):485-498. doi:10.1016/j.cell.2009.09.033

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