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"Collins, Stephanie"
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Bile acids and the gut microbiota: metabolic interactions and impacts on disease
Despite decades of bile acid research, diverse biological roles for bile acids have been discovered recently due to developments in understanding the human microbiota. As additional bacterial enzymes are characterized, and the tools used for identifying new bile acids become increasingly more sensitive, the repertoire of bile acids metabolized and/or synthesized by bacteria continues to grow. Additionally, bile acids impact microbiome community structure and function. In this Review, we highlight how the bile acid pool is manipulated by the gut microbiota, how it is dependent on the metabolic capacity of the bacterial community and how external factors, such as antibiotics and diet, shape bile acid composition. It is increasingly important to understand how bile acid signalling networks are affected in distinct organs where the bile acid composition differs, and how these networks impact infectious, metabolic and neoplastic diseases. These advances have enabled the development of therapeutics that target imbalances in microbiota-associated bile acid profiles.The gut microbiota metabolizes bile acids, thereby influencing human health and diseases including obesity, colitis and cancer. In this Review, Patterson and colleagues discuss host–microbiota interactions and their influence on the bile acid pool as well as therapeutic implications.
Journal Article
Choices : all-new tales of Valdemar
\"The Heralds of Valdemar are the kingdom's ancient order of protectors. They are drawn from all across the land, from all walks of life, and at all ages--and all are Gifted with abilities beyond those of normal men and women. They are Mindspeakers, FarSeers, Empaths, ForeSeers, Firestarters, FarSpeakers, and more. These inborn talents--combined with training as emissaries, spies, judges, diplomats, scouts, counselors, warriors, and more--make them indispensable to their monarch and realm. Sought and Chosen by mysterious horse-like Companions, they are bonded for life to these telepathic, enigmatic creatures. The Heralds of Valdemar and their Companions ride circuit throughout the kingdom, protecting the peace and, when necessary, defending their land and monarch. Now, twenty-three authors ride with Mercedes Lackey to her magical land of Valdemar, adding their own unique voices to the Heralds, Bards, Healers, and other heroes of this beloved fantasy realm.\"--Amazon.com.
Book
Caloric restriction disrupts the microbiota and colonization resistance
Diet is a major factor that shapes the gut microbiome
1
, but the consequences of diet-induced changes in the microbiome for host pathophysiology remain poorly understood. We conducted a randomized human intervention study using a very-low-calorie diet (NCT01105143). Although metabolic health was improved, severe calorie restriction led to a decrease in bacterial abundance and restructuring of the gut microbiome. Transplantation of post-diet microbiota to mice decreased their body weight and adiposity relative to mice that received pre-diet microbiota. Weight loss was associated with impaired nutrient absorption and enrichment in
Clostridioides difficile
, which was consistent with a decrease in bile acids and was sufficient to replicate metabolic phenotypes in mice in a toxin-dependent manner. These results emphasize the importance of diet–microbiome interactions in modulating host energy balance and the need to understand the role of diet in the interplay between pathogenic and beneficial symbionts.
Severe caloric restriction in humans leads to reversible changes in the gut microbiota that promote weight loss and the expansion of an enteric pathogen in mice.
Journal Article
Distinct fecal microbiome between wild and habitat-housed captive polar bears (Ursus maritimus): Impacts of captivity and dietary shifts
Understanding the gut microbiome of polar bears can shed light on the effects of climate change-induced prolonged ice-free seasons on their health and nutritional status as a sentinel species. The fecal microbiome of habitat-housed captive polar bears who had consumed a high protein diet long-term was compared with that of the wild population. Individual differences, season, year and dietary inclusion of a brown seaweed ( Fucus spiralis ; part of the natural diet of wild polar bears), as a representation for nutritional change, were investigated for their effects on the fecal microbiome of captive polar bears. Microbial variations among fecal samples from wild and captive polar bears were investigated using 16s rRNA gene based metataxonomic profiling. The captive bears exhibited more diverse fecal microbiota than wild bears (p<0.05). The difference was due to significantly increased Firmicutes , Campilobacterota and Fusobacteriota , decreased Actinobacteriota (p<0.05), and absent Bdellovibrionota and Verrucomicrobiota in the captive bears. Compared with other factors, individual variation was the main driver of differences in fecal microbial composition in the captive bears. Seaweed consumption did not alter microbial diversity or composition, but this did not rule out dietary influences on the hosts. This is the first study, to the best of our knowledge, comparing the fecal microbiota of captive and wild polar bears and it reveals distinct differences between the two groups, which could result from many factors, including available food sources and the ratio of dietary macronutrients. Our findings provide preliminary insights into climate-change induced dietary shifts in polar bears related to climate-associated habitat change.
Journal Article
Bile salt hydrolase catalyses formation of amine-conjugated bile acids
Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes
1
–
6
; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine
N
-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine
N
-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of
bsh
and mutants in
Escherichia coli
and
bsh
knockout and complementation in
Bacteroides fragilis
to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of
bsh-
expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.
We find that bile salt hydrolase
N
-acyltransferase activity can form bacterial bile acid amidates that are positively correlated with the colonization of gut bacteria that assist in the regulation of the bile acid metabolic network.
Journal Article
Response to Critics
This is a response to the critial comments by Anne Schwenkenbecher, Olle Blomberg, Bill Wringe and Gunnar Björnsson.
Journal Article
Precis of Group Duties: Their Existence and Their Implications for Individuals
This paper provides an overview of Group Duties: Their Existence and Their Implications for Individuals.
Journal Article
Collective Responsibility Gaps
Which kinds of responsibility can we attribute to which kinds of collective, and why? In contrast, which kinds of collective responsibility can we not attribute—which kinds are 'gappy'? This study provides a framework for answering these questions. It begins by distinguishing between three kinds of collective (diffuse, teleological, and agential) and three kinds of responsibility (causal, moral, and prospective). It then explains how gaps—i.e. cases where we cannot attribute the responsibility we might want to—appear to arise within each type of collective responsibility. It argues some of these gaps do not exist on closer inspection, at least for some collectives and some of the time.
Journal Article
Positive clinical outcome using a modified dosing regimen of benznidazole in dogs at high risk for infection or acutely infected with Trypanosoma cruzi
Abstract
Trypanosoma cruzi infection in dogs can cause heart failure and sudden death with few treatment options available. A litter of 4 dogs living in a T cruzi endemic area were randomized to prophylaxis and nonprophylaxis groups as part of a study evaluating a modified benznidazole dosing regimen administered twice weekly to prevent T cruzi infection during a vector transmission season. The 2 dogs that received prophylaxis remained healthy without T cruzi infection or cardiac disease for >2 years. One dog that did not receive prophylaxis died unexpectedly with acute T cruzi–induced pancarditis, and the second dog tested positive for T cruzi and developed complex arrhythmias with markedly increased cardiac troponin I and improved with a higher benznidazole treatment dose. Although the small sample size precludes definitive conclusions, we describe the potential clinical benefit of prophylactic and early treatment with modified benznidazole dosing regimens for dogs with T cruzi infection.
Journal Article