Dialogue between the microbiome and immune system

Segmented filamentous bacteria (SFB) and its ability to protect against infection

The dialogue between our body and intestinal microbiome is a crucial component of our health that begins at birth and continues throughout life. A key period is weaning, when a newborn diversifies his or her diet, allowing numerous new microbial species to colonize the digestive tract. These new arrivals include a species of bacteria that has particularly caught the attention of researches in recent years: segmented filamentous bacteria (SFB).

Identified in the gut of numerous invertebrate and vertebrate species (termites, trout, rodents, pigs, primates, humans), this bacteria has the distinct characteristic of attaching itself to the intestinal cells, sending a strong signal to the immune system.^1–6 Even though our immune system is programmed to alert the entire body in the event of an unexpected encounter, SFB’s attachment to the intestinal lining does not trigger disease or fever in healthy subjects. On the contrary, research has shown that, in rodents, this bacteria contributes to reinforcing the tonicity of the immune system, in particular by helping prepare the body’s defenses, thereby increasing resistance to bacterial infections.³

Very recently, researchers from various teams have been able to demonstrate that SFB can even induce a powerful signal to protect against and/or cure colitis caused by viruses.^7-7b This research on mice recognizes the importance that certain species of bacteria in the microbiome might have for humans during intestinal infections caused by viruses. One study focuses on the protective effect of SFB against rotavirus, a major cause of outbreaks of gastroenteritis around the world. Rotavirus affects an average of 140 million people annually, young children in particular, and causes some 500,000 deaths worldwide every year (INRS – ANSES). The mechanisms by which SFB acts against this virus are not fully understood but appear to involve the accelerated renewal of the layer of cells that line the intestinal lumen, known as intestinal epithelial cells. The involvement of these cells in the phenomena of resistance to infection by this virus has not been documented until now. This research, while preliminary, opens up new avenues for the preventative and/or curative treatment of rotavirus infections in humans that may involve the microbiome. Caution is nevertheless advised since the presence of SFB in the intestines of rodents has also been associated with autoimmune diseases such as encephalitis and arthritis.^8,9 Additional research is thus necessary to understand how to exploit the protective effects of certain species in the microbiome such as SFB against infections while simultaneously limiting the collateral damage of a subsequent excessive immune response.¹⁰

1. Klaasen, H. L. B. M. et al. Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species. Lab. Anim. 27, 141–150 (1993).

2. Gaboriau-Routhiau, V. et al. The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses. Immunity 31, 677–689 (2009).

3. Ivanov, I. I. et al. Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria. Cell 139, 485–498 (2009).

4. Schnupf, P. et al. Growth and host interaction of mouse segmented filamentous bacteria in vitro. Nature 520, 99–103 (2015).

5. Prakash, T. et al. Complete Genome Sequences of Rat and Mouse Segmented Filamentous Bacteria, a Potent Inducer of Th17 Cell Differentiation. Cell Host Microbe 10, 273–284 (2011).

6. Yin, Y. et al. Comparative analysis of the distribution of segmented filamentous bacteria in humans, mice and chickens. ISME J. 7, 615–621 (2013).

7. Bolsega, S. et al. Composition of the Intestinal Microbiota Determines the Outcome of Virus-Triggered colitis in Mice. Frontiers in Immunology 10, 1708 (2019)

7b. Shi, Z. et al. Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection. Cell 179, 644-658.e13 (2019).

8. Teng, F. et al. Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer’s Patch T Follicular Helper Cells. Immunity 44, 875–888 (2016).

9. Lee, Y. K., Menezes, J. S., Umesaki, Y. & Mazmanian, S. K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. 108, 4615–4622 (2011).

10. Flannigan, K. L. & Denning, T. L. Segmented filamentous bacteria-induced immune responses: a balancing act between host protection and autoimmunity. Immunology 154, 537–546 (2018).