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Isolation and structural identification of glycopolymers of Bifidobacterium bifidum BIM B-733D as putative players in pathogenesis of autoimmune thyroid diseases

Kiseleva, E. P. ; Mikhailopulo, K. I. ; Novik, G. I. ; Dey, Estera LU ; Zdorovenko, E. L. ; Shashkov, A. S. and Knirel, Y. A. (2013) In Beneficial microbes 4(4). p.375-391
Abstract
Bifidobacterium bifidum 791 (commercially available as B. bifidum BIM B-733D) cell-surface biopolymers (BPs) interact selectively with human serum thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies (anti-TPO and anti-Tg, respectively). BPanti-TPO and BPanti-Tg were isolated from the soluble fraction of B. bifidum BIM B-733D by affinity chromatography with anti-TPO or anti-Tg, respectively. Homogeneity of affinity eluates (AE(anti-TPO) and AE(anti-Tg)) was tested by size exclusion chromatography. For each AE, the elution profiles generated on the basis of absorbance at 280 nm do not conform to ELISA data for functional activity characteristic of BPs. Moreover, high functional activity was detected in chromatographic fractions... (More)
Bifidobacterium bifidum 791 (commercially available as B. bifidum BIM B-733D) cell-surface biopolymers (BPs) interact selectively with human serum thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies (anti-TPO and anti-Tg, respectively). BPanti-TPO and BPanti-Tg were isolated from the soluble fraction of B. bifidum BIM B-733D by affinity chromatography with anti-TPO or anti-Tg, respectively. Homogeneity of affinity eluates (AE(anti-TPO) and AE(anti-Tg)) was tested by size exclusion chromatography. For each AE, the elution profiles generated on the basis of absorbance at 280 nm do not conform to ELISA data for functional activity characteristic of BPs. Moreover, high functional activity was detected in chromatographic fractions that had significantly different molecular weights and no absorbance at 280 nm, which suggests a non-protein (carbohydrate) nature of BPanti-TPO and BPanti-Tg. The semi-preparative size exclusion chromatography of AE(anti-TPO) and AE(anti-Tg) with detection by refractometer gave 5,000-7,000 Da fractions containing substances that interact selectively with either anti-TPO (BPanti-TPO) or anti-Tg (BPanti-Tg) according to ELISA data. Analysis by two-dimensional NMR spectroscopy including a H-1, C-13-heteronuclear single-quantum coherence experiment indicated that both substances are linear alpha-1,6-glucans. For the first time, an immunological similarity (molecular mimicry) of glycopolymers of B. bifidum BIM B-733D and human thyroid proteins, TPO and Tg, was shown. On the whole, our data point to a possible role of bifidobacteria in the pathogenesis of autoimmune thyroid diseases (ATD). The main requirements for triggering/acceleration or prevention/abrogation of ATD by bifidobacteria through molecular mimicry mechanism are hypothesised to be (1) genetic predisposition to ATD and (2) intestinal epithelium penetration by alpha-1,6-glucan. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
molecular mimicry, 6-glucan, alpha-1, autoantibodies
in
Beneficial microbes
volume
4
issue
4
pages
375 - 391
publisher
Wageningen Academic Publishers
external identifiers
  • wos:000328272900009
  • scopus:84891588241
  • pmid:24311320
ISSN
1876-2891
DOI
10.3920/BM2013.0015
language
English
LU publication?
yes
id
342737b2-cda5-4828-8926-3b05313c0613 (old id 4272738)
date added to LUP
2016-04-01 10:50:49
date last changed
2022-04-04 21:51:40
@article{342737b2-cda5-4828-8926-3b05313c0613,
  abstract     = {{Bifidobacterium bifidum 791 (commercially available as B. bifidum BIM B-733D) cell-surface biopolymers (BPs) interact selectively with human serum thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies (anti-TPO and anti-Tg, respectively). BPanti-TPO and BPanti-Tg were isolated from the soluble fraction of B. bifidum BIM B-733D by affinity chromatography with anti-TPO or anti-Tg, respectively. Homogeneity of affinity eluates (AE(anti-TPO) and AE(anti-Tg)) was tested by size exclusion chromatography. For each AE, the elution profiles generated on the basis of absorbance at 280 nm do not conform to ELISA data for functional activity characteristic of BPs. Moreover, high functional activity was detected in chromatographic fractions that had significantly different molecular weights and no absorbance at 280 nm, which suggests a non-protein (carbohydrate) nature of BPanti-TPO and BPanti-Tg. The semi-preparative size exclusion chromatography of AE(anti-TPO) and AE(anti-Tg) with detection by refractometer gave 5,000-7,000 Da fractions containing substances that interact selectively with either anti-TPO (BPanti-TPO) or anti-Tg (BPanti-Tg) according to ELISA data. Analysis by two-dimensional NMR spectroscopy including a H-1, C-13-heteronuclear single-quantum coherence experiment indicated that both substances are linear alpha-1,6-glucans. For the first time, an immunological similarity (molecular mimicry) of glycopolymers of B. bifidum BIM B-733D and human thyroid proteins, TPO and Tg, was shown. On the whole, our data point to a possible role of bifidobacteria in the pathogenesis of autoimmune thyroid diseases (ATD). The main requirements for triggering/acceleration or prevention/abrogation of ATD by bifidobacteria through molecular mimicry mechanism are hypothesised to be (1) genetic predisposition to ATD and (2) intestinal epithelium penetration by alpha-1,6-glucan.}},
  author       = {{Kiseleva, E. P. and Mikhailopulo, K. I. and Novik, G. I. and Dey, Estera and Zdorovenko, E. L. and Shashkov, A. S. and Knirel, Y. A.}},
  issn         = {{1876-2891}},
  keywords     = {{molecular mimicry; 6-glucan; alpha-1; autoantibodies}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{375--391}},
  publisher    = {{Wageningen Academic Publishers}},
  series       = {{Beneficial microbes}},
  title        = {{Isolation and structural identification of glycopolymers of Bifidobacterium bifidum BIM B-733D as putative players in pathogenesis of autoimmune thyroid diseases}},
  url          = {{http://dx.doi.org/10.3920/BM2013.0015}},
  doi          = {{10.3920/BM2013.0015}},
  volume       = {{4}},
  year         = {{2013}},
}