The Role of Segmented Filamentous Bacteria in Immune Barrier Maturation of the Small Intestine at Weaning

The microbiological, physical, chemical, and immunological barriers of the gastrointestinal tract (GIT) begin developing in utero and finish maturing postnatally. Maturation of these barriers is essential for the proper functioning of the GIT. Maturation, particularly of the immunological barrier, involves stimulation by bacteria. Segmented filamentous bacteria (SFB) which are anaerobic, spore-forming commensals have been linked to immune activation. The presence and changes in SFB abundance have been positively correlated to immune markers (cytokines and immunoglobulins) in the rat ileum and stool samples, pre- and post-weaning. The abundance of SFB in infant stool increases from 6 months, peaks around 12 months and plateaus 25 months post-weaning. Changes in SFB abundance at these times correlate positively and negatively with the production of interleukin 17 (IL 17) and immunoglobulin A (IgA), respectively, indicating involvement in immune function and maturation. Additionally, the peak in SFB abundance when a human milk diet was complemented by solid foods hints at a diet effect. SFB genome analysis revealed enzymes involved in metabolic pathways for survival, growth and development, host mucosal attachment and substrate acquisition. This narrative review discusses the current knowledge of SFB and their suggested effects on the small intestine immune system. Referencing the published genomes of rat and mouse SFB, the use of food substrates to modulate SFB abundance is proposed while considering their effects on other microbes. Changes in the immune response caused by the interaction of food substrate with SFB may provide insight into their role in infant immunological barrier maturation.

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Whole tissue homogenization preferable to mucosal scraping in determining the temporal profile of segmented filamentous bacteria in the ileum of weanling rats

Access Microbiology ◽

10.1099/acmi.0.000218 ◽

2021 ◽

Vol 3 (3) ◽

Author(s):

Linda A. Oemcke ◽

Rachel C. Anderson ◽

Jasna Rakonjac ◽

Warren C. McNabb ◽

Nicole C. Roy

Keyword(s):

Immunoglobulin A ◽

Interleukin 17 ◽

Filamentous Bacteria ◽

Sprague Dawley ◽

Suitable Alternative ◽

Segmented Filamentous Bacteria ◽

Sprague Dawley Rats ◽

Weanling Rats ◽

Ileal Tissue ◽

Mucosal Scraping

Segmented filamentous bacteria (SFB) are thought to play a role in small intestine immunological maturation. Studies in weanling mice have shown a positive correlation between ileal SFB abundance and plasma and faecal interleukin 17 (IL-17) and immunoglobulin A (IgA) concentrations. Although the first observation of SFB presence was reported in rats, most studies use mice. The size of the mouse ileum is a limitation whereas the rat could be a suitable alternative for sufficient samples. Changes in SFB abundance over time in rats were hypothesized to follow the pattern reported in mice and infants. We characterized the profile of SFB colonization in the ileum tissue and contents and its correlation with two immune markers of gastrointestinal tract (GIT) maturation. We also compared two published ileum collection techniques to determine which yields data on SFB abundance with least variability. Whole ileal tissue and ileal mucosal scrapings were collected from 20- to 32-day-old Sprague-Dawley rats. SFB abundance was quantified from proximal, middle and distal ileal tissues, contents and faeces by quantitative PCR using SFB-specific primers. Antibody-specific ELISAs were used to determine IL-17 and IgA concentrations. Significant differences in SFB abundance were observed from whole and scraped tissues peaking at day 22. Variability in whole ileum data was less, favouring it as a better collection technique. A similar pattern of SFB abundance was observed in ileum contents and faeces peaking at day 24, suggesting faeces can be a proxy for ileal SFB abundance. SFB abundance at day 26 was higher in females than males across all samples. There were significant differences in IgA concentration between days 20, 30 and 32 and none in IL-17 concentration, which was different from reports in mice and infants.

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Differential Roles of Segmented Filamentous Bacteria and Clostridia in Development of the Intestinal Immune System

Infection and Immunity ◽

10.1128/iai.67.7.3504-3511.1999 ◽

1999 ◽

Vol 67 (7) ◽

pp. 3504-3511 ◽

Cited By ~ 169

Author(s):

Yoshinori Umesaki ◽

Hiromi Setoyama ◽

Satoshi Matsumoto ◽

Akemi Imaoka ◽

Kikuji Itoh

Keyword(s):

Small Intestine ◽

Immune System ◽

Large Intestine ◽

Immunoglobulin A ◽

Cell Receptor ◽

Intraepithelial Lymphocytes ◽

Filamentous Bacteria ◽

Segmented Filamentous Bacteria ◽

Intestinal Immune System ◽

Gnotobiotic Mice

ABSTRACT The presence of microflora in the digestive tract promotes the development of the intestinal immune system. In this study, to evaluate the roles of two types of indigenous microbe, segmented filamentous bacteria (SFB) and clostridia, whose habitats are the small and large intestines, respectively, in this immunological development, we analyzed three kinds of gnotobiotic mice contaminated with SFB, clostridia, and both SFB and clostridia, respectively, in comparison with germfree (GF) or conventionalized (Cvd) mice associated with specific-pathogen-free flora. In the small intestine, the number of αβ T-cell receptor-bearing intraepithelial lymphocytes (αβIEL) increased in SFB-associated mice (SFB-mice) but not in clostridium-associated mice (Clost-mice). There was no great difference in Vβ usage among GF mice, Cvd mice, and these gnotobiotic mice, although the association with SFB decreased the proportion of Vβ6+ cells in CD8β− subsets to some extent, compared to that in GF mice. The expression of major histocompatibility complex class II molecules on the epithelial cells was observed in SFB-mice but not in Clost-mice. On the other hand, in the large intestine, the ratio of the number of CD4−CD8+ cells to that of CD4+ CD8−cells in αβIEL increased in Clost-mice but not in SFB-mice. On association with both SFB and clostridia, the numbers and phenotypes of IEL in the small and large intestines changed to become similar to those in Cvd mice. In particular, the ratio of the number of CD8αβ+ cells to that of CD8αα+ cells in αβIEL, unusually elevated in the small intestines of SFB-mice, decreased to the level in Cvd mice on contamination with both SFB and clostridia. The number of immunoglobulin A (IgA)-producing cells in the lamina propria was more elevated in SFB-mice than in Clost-mice, not only in the ileum but also in the colon. The number of IgA-producing cells in the colons of Clost-mice was a little increased compared to that in GF mice. Taken together, SFB and clostridia promoted the development of both IEL and IgA-producing cells in the small intestine and that of only IEL in the large intestine, respectively, suggesting the occurrence of compartmentalization of the immunological responses to the indigenous bacteria between the small and large intestines.

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Pharmacological Rationale for Targeting IL-17 in Asthma

Frontiers in Allergy ◽

10.3389/falgy.2021.694514 ◽

2021 ◽

Vol 2 ◽

Author(s):

Siti Farah Rahmawati ◽

Maurice te Velde ◽

Huib A. M. Kerstjens ◽

Alexander S. S. Dömling ◽

Matthew Robert Groves ◽

...

Keyword(s):

Severe Asthma ◽

Inhaled Corticosteroids ◽

Current Knowledge ◽

Experimental Models ◽

Airflow Limitation ◽

Interleukin 17 ◽

Asthma Phenotype ◽

T Helper 2 ◽

Bronchial Biopsies

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

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Segmented filamentous bacteria in the rodent small intestine: Their colonization of growing animals and possible role in host resistance toSalmonella

Microbial Ecology ◽

10.1007/bf02010451 ◽

1982 ◽

Vol 8 (2) ◽

pp. 181-190 ◽

Cited By ~ 56

Author(s):

Christian D. Garland ◽

Adrian Lee ◽

Melvyn R. Dickson

Keyword(s):

Small Intestine ◽

Host Resistance ◽

Filamentous Bacteria ◽

Segmented Filamentous Bacteria

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Segmented Filamentous Bacteria Are Potent Stimuli of a Physiologically Normal State of the Murine Gut Mucosal Immune System

Infection and Immunity ◽

10.1128/iai.67.4.1992-2000.1999 ◽

1999 ◽

Vol 67 (4) ◽

pp. 1992-2000 ◽

Cited By ~ 241

Author(s):

Gwen L. Talham ◽

Han-Qing Jiang ◽

Nicolaas A. Bos ◽

John J. Cebra

Keyword(s):

T Cells ◽

Immune System ◽

Immunoglobulin A ◽

Mucosal Immune System ◽

Filamentous Bacteria ◽

Mesenteric Lymph Nodes ◽

Segmented Filamentous Bacteria ◽

Iga Antibody ◽

Autochthonous Bacteria ◽

Iga Production

ABSTRACT Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the intestinal tracts of many species, including humans. We studied the effect of SFB on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice with SFB. At various time points during 190 days of colonization, fragment cultures of small intestine and Peyer’s patches (PP) were analyzed for total immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes indicating germinal center reactions (GCRs) and the activation of CD4+ T cells in PP were determined by using fluorescence-activated cell sorter analyses. A second group of SFB-monoassociated mice was colonized with a gram-negative commensal,Morganella morganii, to determine if the mucosal immune system was again stimulated and to evaluate the effect of prior colonization with SFB on the ability of M. morganii to translocate to the spleen and mesenteric lymph nodes. We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that GCRs only gradually waned over the entire length of colonization, that natural IgA production was increased to levels 24 to 63% of that of conventionally reared mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of total IgA. Also, the proportion of CD4+, CD45RBlow T cells, indicative of activated cells, gradually increased in the PP to the level found in conventionally reared mice. Secondary colonization with M. morganii was able to stimulate GCRs anew, leading to a specific IgA antibody response. Previous stimulation of mucosal immunity by SFB did not prevent the translocation of M. morganii in the double-colonized mice. Our findings generally indicate that SFB are one of the single most potent microbial stimuli of the gut mucosal immune system.

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The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses

Immunity ◽

10.1016/j.immuni.2009.08.020 ◽

2009 ◽

Vol 31 (4) ◽

pp. 677-689 ◽

Cited By ~ 912

Author(s):

Valérie Gaboriau-Routhiau ◽

Sabine Rakotobe ◽

Emelyne Lécuyer ◽

Imke Mulder ◽

Annaïg Lan ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Filamentous Bacteria ◽

Helper T Cell ◽

Cell Responses ◽

Segmented Filamentous Bacteria

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Role of interleukin-23/interleukin-17 axis in T-cell-mediated actions in hypertension

Cardiovascular Research ◽

10.1093/cvr/cvaa257 ◽

2020 ◽

Author(s):

Akinori Higaki ◽

Ahmad U M Mahmoud ◽

Pierre Paradis ◽

Ernesto L Schiffrin

Keyword(s):

Observational Studies ◽

Current Knowledge ◽

Interleukin 17 ◽

Preclinical Studies ◽

Rodent Models ◽

Blood Pressure Elevation ◽

Immune Mechanisms ◽

Treatment Of Hypertension ◽

Interleukin 23

Abstract Current knowledge suggests that hypertension is in part mediated by immune mechanisms. Both interleukin (IL)-23 and IL-17 are up-regulated in several experimental hypertensive rodent models, as well as in hypertensive humans in observational studies. Recent preclinical studies have shown that either IL-23 or IL-17A treatment induce blood pressure elevation. However, the IL-23/IL-17 axis has not been a major therapeutic target in hypertension, unlike in other autoimmune diseases. In this review, we summarize current knowledge on the role of these cytokines in immune mechanisms contributing to hypertension, and discuss the potential of IL-23/IL-17-targeted therapy for treatment of hypertension.

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Interactions between gut-associated lymphoid tissue and colonization levels of indigenous, segmented, filamentous bacteria in the small intestine of mice

Canadian Journal of Microbiology ◽

10.1139/w98-122 ◽

1998 ◽

Vol 44 (12) ◽

pp. 1177-1182 ◽

Cited By ~ 26

Author(s):

J Snel ◽

C C Hermsen ◽

H J Smits ◽

N A Bos ◽

WMC Eling ◽

...

Keyword(s):

Small Intestine ◽

Immune System ◽

Lymphoid Tissue ◽

Immune Reaction ◽

Mucosal Immune System ◽

Filamentous Bacteria ◽

Segmented Filamentous Bacteria ◽

Swiss Mice ◽

Age Dependent ◽

Old Mice

Unlike most other indigenous bacteria, segmented filamentous bacteria (SFB) are potent activators of the mucosal immune system. SFB are strongly anchored to the epithelial cells of the small intestine where they have a preference for mucosal lymphoid epithelium. Since SFB are only present in high numbers shortly after weaning, it was investigated whether an SFB-induced immune reaction results in the removal of these bacteria from the small intestine. A correlation was found between age and colonization levels in the small intestines of SFB monoassociated Swiss mice. Five-week-old athymic BALB/c (nu/nu) mice showed lower colonization levels than their heterozygous littermates, but the opposite was found at the age of 12 weeks. However, SFB inoculation of germfree Swiss mice resulted in higher colonization levels in 5-week-old mice when compared with 4-month-old mice. We conclude that SFB colonization levels in the small intestine are likely influenced by the activity of the mucosal immune system. However, an additional age-dependent factor that modulates SFB colonization levels cannot be excluded.Key words: segmented filamentous bacteria, small intestine, gut-associated lymphoid tissue.

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