High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE-/-mice.
Atherosclerosis appears to have multifactorial causes - microbial component like lipopolysaccharides (LPS) and other pathogen associated molecular patterns may be plausible factors. The gut microbiota is an ample source of such stimulants, and its dependent metabolites and altered gut metagenome has been an established link to atherosclerosis. In this exploratory pilot study, we aimed to elucidate whether microbial intervention with probiotics L. rhamnosus GG (LGG) or pharmaceuticals telmisartan (TLM) could improve atherosclerosis in a gut microbiota associated manner.



Atherosclerotic phenotype was established by 12 weeks feeding of high fat (HF) diet as opposed to normal chow diet (ND) in apolipoprotein E knockout (ApoE-/-) mice. LGG or TLM supplementation to HF diet was studied.



Both LGG and TLM significantly reduced atherosclerotic plaque size and improved various biomarkers including endotoxin to different extents. Colonial microbiota analysis revealed that TLM restored HF diet induced increase in Firmicutes/Bacteroidetes ratio and decrease in alpha diversity; and led to a more distinct microbial clustering closer to ND in PCoA plot. Eubacteria, Anaeroplasma, Roseburia, Oscillospira and Dehalobacteria appeared to be protective against atherosclerosis and showed significant negative correlation with atherosclerotic plaque size and plasma adipocyte - fatty acid binding protein (A-FABP) and cholesterol.



LGG and TLM improved atherosclerosis with TLM having a more distinct alteration in the colonic gut microbiota. Altered bacteria genera and reduced alpha diversity had significant correlations to atherosclerotic plaque size, plasma A-FABP and cholesterol. Future studies on such bacterial functional influence in lipid metabolism will be warranted.
5S12, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong. cyk.carol@hotmail.com.
Yee Kwan
YK
Chan
5N01, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong. manreet@hku.hk.
Manreetpal Singh
MS
Brar
Food and Research Health Centre, University of Eastern Finland, Joensuu, Finland.
Pirkka V
PV
Kirjavainen
L943, Laboratory Block, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
Yan
Y
Chen
L943, Laboratory Block, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
Jiao
J
Peng
L943, Laboratory Block, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
Daxu
D
Li
5N01, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong.|Bioinformatics Center, Nanjing Agricultural University, Nanjing, China.
Frederick Chi-Ching
FC
Leung
5S12, Kadoorie Biological Sciences Building, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong. elnezami@hku.hk.|Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. elnezami@hku.hk.|5S13, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong. elnezami@hku.hk.
Hani
H
El-Nezami
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood*; D003106:Colon / Q000382:microbiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D052201:Lacticaseibacillus rhamnosus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010865:Pilot Projects; D019936:Probiotics / Q000008:administration & dosage*; D000077333:Telmisartan
D001057:Apolipoproteins E; D001562:Benzimidazoles; D001565:Benzoates; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D002784:Cholesterol; D000077333:Telmisartan
Atherosclerosis; Gut microbitoa; LGG; Probiotics; Telmisartan