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. 2021 Nov 27;9:235. doi: 10.1186/s40168-021-01181-z

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — Effect of long-term TMAO exposure on BBB integrity and cognitive function of mice in conjunction with sub-acute inflammatory challenge. A Body weight gain in mice treated with TMAO through their drinking water (0.5 mg/ml) over 2 months, combined with a chronic low-dose administration of LPS (0.5 mg/kg/week, i.p.). Data are expressed as mean ± s.e.m., n = 8 mice, columns with different letters are significantly different at P < 0.05. B Cerebellar permeability index to sodium fluorescein 2h following administration in animals previously treated with TMAO through their drinking water (0.5 mg/ml) over 2 months, combined with a chronic low-dose administration of LPS (0.5 mg/kg/week, i.p.). Data are expressed as mean ± s.e.m., n = 8 mice, columns with different letters are significantly different at P < 0.05. C Typical confocal microscopic images of perivascular IgG deposition in male C57Bl/6J mice treated with TMAO through their drinking water (0.5 mg/ml) over 2 months, combined with a chronic low-dose administration of LPS (0.5 mg/kg/week, i.p.). Griffonia simplicifolia isolectin B₄ (red) defines endothelial cells, areas of IgG deposition (white) are highlighted by arrow heads. D Distance travelled, E movement speed and F percentage of time in the centre as measured in the OFT in animals previously treated with TMAO through their drinking water (0.5 mg/ml) over 2 months, combined with a chronic low-dose administration of LPS (0.5 mg/kg/week, i.p.). Data are expressed as mean ± s.e.m., n = 8 mice. G Novel object discrimination index, calculated as described in Methods, of animals previously treated with TMAO through their drinking water (0.5 mg/ml) over 2 months, combined with a chronic low-dose administration of LPS (0.5 mg/kg/week, i.p.). Data are expressed as mean ± s.e.m., n = 8 mice, columns with different letters are significantly different at P < 0.05. H Percentage of spontaneous alternation and I total distance travelled in the Y-maze test for animals previously treated with TMAO through their drinking water (0.5 mg/ml) over 2 months, combined with a chronic low-dose administration of LPS (0.5 mg/kg/week, i.p.). Data are expressed as mean ± s.e.m., n = 8 mice