Differential Effects of Sulfur Amino Acid-Restricted and Low-Calorie Diets on Gut Microbiome Profile and Bile Acid Composition in Male C57BL6/J Mice

Abstract Diet can affect health and longevity by altering the gut microbiome profile. Sulfur amino acid restriction (SAAR), like caloric restriction, extends lifespan. But, its effect on the gut microbiome profile and functional significance of such effects are understudied. We investigated whether SAAR alters the gut microbiome profile and bile acid composition, an index of microbial metabolism. We also compared these changes with those induced by a 12% low-calorie diet (LCD). Male 21-week-old C57BL6/J mice were fed control (CD; 0.86% methionine), SAAR (0.12% methionine), and LCD diets (0.86% methionine). After 10 weeks on the diet, plasma markers and fecal microbial profiles were determined. SAAR mice had lower body weights and IGF-1, and higher food intake and FGF-21 than CD mice. Compared to SAAR mice, LCD mice had higher body weights, and lower FGF-21 and food intake, but similar IGF-1. β-Diversity indices were different between SAAR and LCD, and LCD and CD, but not between CD and SAAR. In groupwise comparisons of individual taxa, differences were more discernable between SAAR and LCD than between other groups. Abundances of Firmicutes, Clostridiaceae, and Turicibacteraceae were higher, but Verrucomicrobia was lower in SAAR than in LCD. Secondary bile acids and the ratio of secondary to primary bile acids were lower in SAAR than in LCD. SAAR favored bile acid conjugation with glycine at the expense of taurine. Overall, SAAR and LCD diets induced distinct changes in the gut microbiome and bile acid profiles. Additional studies on the role of these changes in improving health and lifespan are warranted.

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Structural Basis for Human Norovirus Capsid Binding to Bile Acids

Journal of Virology ◽

10.1128/jvi.01581-18 ◽

2018 ◽

Vol 93 (2) ◽

Cited By ~ 23

Author(s):

Turgay Kilic ◽

Anna Koromyslova ◽

Grant S. Hansman

Keyword(s):

Bile Acid ◽

Amino Acid ◽

Bile Acids ◽

Natural Infection ◽

Structural Basis ◽

Amino Acid Side Chain ◽

Blood Group Antigens ◽

Human Norovirus ◽

Bile Acid Binding ◽

P Domain

ABSTRACT A recently developed human norovirus cell culture system revealed that the presence of bile enhanced or was an essential requirement for the growth of certain genotypes. Before this discovery, histo-blood group antigens (HBGAs) were the only well-studied cofactor known for human noroviruses, and there was evidence that several genotypes poorly bound HBGAs. Therefore, the purpose of this study was to investigate how human norovirus capsids interact with bile acids. We found that bile acids had low-micromolar affinities for GII.1, GII.10, and GII.19 capsids but did not bind GI.1, GII.3, GII.4, or GII.17. We showed that bile acid bound at a partially conserved pocket on the norovirus capsid-protruding (P) domain using X-ray crystallography. Amino acid sequence alignment and structural analysis delivered an explanation of selective bile acid binding. Intriguingly, we discovered that binding of the bile acid was the critical step to stabilize several P domain loops that optimally placed an essential amino acid side chain (Asp375) to bind HBGAs in an otherwise HBGA nonbinder (GII.1). Furthermore, bile acid enhanced HBGA binding for a known HBGA binder (GII.10). Altogether, these new data suggest that bile acid functions as a loop-stabilizing regulator and enhancer of HBGA binding for certain norovirus genotypes. IMPORTANCE Given that human norovirus virions likely interact with bile acid during a natural infection, our evidence that an HBGA nonbinder (GII.1) can be converted to an HBGA binder after bile acid binding is of major significance. Our data provide direct evidence that, like HBGAs, bile acid interaction on the capsid is an important cofactor for certain genotypes. However, more unanswered questions seem to arise from these new discoveries. For example, is there an association between the bile acid requirement and the prevalence of certain genotypes? That is, the GII.1 and GII.10 (bile acid binders) genotypes rarely caused outbreaks, whereas the GII.4 and GII.17 genotypes (bile acid nonbinders) were responsible for large epidemics. Therefore, it seems plausible that certain genotypes require bile acids, whereas others have modified their bile acid requirements on the capsid.

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Bile Acid Coenzyme A: Amino Acid N‐Acyltransferase in the Amino Acid Conjugation of Bile Acids

Methods in Enzymology - Phase II Conjugation Enzymes and Transport Systems ◽

10.1016/s0076-6879(05)00022-4 ◽

2005 ◽

pp. 374-394 ◽

Cited By ~ 11

Author(s):

Erin M. Shonsey ◽

Mindan Sfakianos ◽

Michelle Johnson ◽

Dongning He ◽

Charles N. Falany ◽

...

Keyword(s):

Bile Acid ◽

Amino Acid ◽

Bile Acids ◽

Coenzyme A

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Abstract P473: Obstructive Sleep Apnea Results In Microbial Bile Acid Biotransformations To Promote Atherosclerosis

Circulation Research ◽

10.1161/res.129.suppl_1.p473 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Amulya Lingaraju ◽

Stephany Flores Ramos ◽

Emily Gentry ◽

Orit Poulsen ◽

Pieter C Dorrestein ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Bile Acid ◽

Sleep Apnea ◽

Bile Acids ◽

Gut Microbiome ◽

Atherosclerotic Lesion ◽

Farnesoid X Receptor ◽

Lesion Formation ◽

Aortic Lesion ◽

Obstructive Sleep

Obstructive sleep apnea (OSA) is an independent exacerbator of cardiovascular disease (CVD). However, it is unclear how OSA or it’s characteristic components, intermittent hypoxia and hypercapnia (IHC), increase CVD risk. Our previous work has shown that IHC reproducibly changes the gut microbiome dynamics in murine models of atherosclerosis and that these changes could affect host cardiovascular physiology through bile acids and phosphocholines. In our initial targeted metabolomics approach, changes in particular bile acids, such as taurocholic acid, taurodeoxycholic acid, and muricholic acid, were associated with and were predictive of IHC exposure in atherosclerotic Ldlr-/- mice. In a more recent study, we identified the formation of novel, microbially-synthesized conjugated bile acids by the gut microbiome that are more potent farnesoid X receptor agonists than other previously described bile acids, and thus, potentially can affect atherosclerosis formation. To determine whether these novel bile acids are associated with IHC-induced atherosclerosis, we characterized luminal bile acid changes in Ldlr-/- mice in an OSA model. We hypothesize that IHC alters the amount of microbially-synthesized novel bile acids and that these bile acids are associated with IHC-induced atherosclerosis. To test this hypothesis, we subjected atherogenic diet-fed Ldlr-/- mice to either room-air (control) or IHC conditions (n=10/condition) and assessed atherosclerotic lesion formation after 12 weeks post-diet. Mice under IHC conditions had significantly higher aortic lesion formation compared to controls. Assessment of fecal bile acid metabolites indicated changes in novel bile acid levels under IHC conditions. Moreover, correlational analysis showed that these novel bile acid changes were positively correlated with atherosclerotic lesion amounts, mainly driven by IHC conditions. Our results demonstrate that bile acid changes through microbial biotransformations occur under IHC conditions and could be the mechanistic link between OSA-induced microbiome changes and atherosclerosis.

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Molecular Physiology of Bile Acid Signaling in Health, Disease and Aging

Physiological Reviews ◽

10.1152/physrev.00049.2019 ◽

2020 ◽

Cited By ~ 2

Author(s):

Alessia Perino ◽

Hadrien Demagny ◽

Laura Alejandra Velazquez-Villegas ◽

Kristina Schoonjans

Keyword(s):

Bile Acid ◽

Gut Microbiota ◽

Bile Acids ◽

Gut Microbiome ◽

Signaling Molecules ◽

Therapeutic Strategies ◽

Fine Tuning ◽

Physiological Effects ◽

Adaptive Responses ◽

Molecular Physiology

Over the last two decades, bile acids (BAs) have become established as important signaling molecules that enable fine-tuned inter-tissue communication from the liver, their site of production, over the intestine, where they are modified by the gut microbiota, to virtually any organ, where they exert their pleiotropic physiological effects. The chemical variety of BAs, to a large extent determined by the gut microbiome, also allows for a complex fine-tuning of adaptive responses in our body. This review provides an overview of the mechanisms by which BA receptors coordinate several aspects of physiology and highlights new therapeutic strategies for diseases underlying pathological BA signaling.

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