Gut Microbiota-Dependent Modulation of Energy Metabolism

Heiss, Christina N.; Olofsson, Louise E.

doi:10.1159/000481519

Cited by 220 publications

(181 citation statements)

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“…During recent decades, the development of high‐throughput sequencing technology has enabled scientists to perform metagenomic studies, which have hugely contributed to our increased understanding of host‐microbe interaction in health and disease . The microbiota is now recognised as an environmental factor that affects the physiology of the host by playing important roles in, for example host immunity, metabolism and behaviour …”

Section: The Human Microbiotamentioning

confidence: 99%

“…In the gut, microbes metabolise otherwise indigestible complex carbohydrates producing short‐chain fatty acids (SCFAs). The SCFAs can be absorbed by the host and utilised as energy . However, the SCFAs can also act as signalling molecules and, as discussed below, the SCFAs are important for the maturation of the microglia in the CNS .…”

Section: Microbial Signalling To the Cns And The Ensmentioning

confidence: 99%

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The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

Heiss

Olofsson

2019

J Neuroendocrinology

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The gut microbiota has emerged as an environmental factor that modulates the development of the central nervous system (CNS) and the enteric nervous system (ENS). Before obtaining its own microbiota, eutherian foetuses are exposed to products and metabolites from the maternal microbiota. At birth, the infants are colonised by microorganisms. The microbial composition in early life is strongly influenced by the mode of delivery, the feeding method, the use of antibiotics and the maternal microbial composition. Microbial products and microbially produced metabolites act as signalling molecules that have direct or indirect effects on the CNS and the ENS. An increasing number of studies show that the gut microbiota can modulate important processes during development, including neurogenesis, myelination, glial cell function, synaptic pruning and blood‐brain barrier permeability. Furthermore, numerous studies indicate that there is a developmental window early in life during which the gut microbial composition is crucial and perturbation of the gut microbiota during this period causes long‐lasting effects on the development of the CNS and the ENS. However, other functions are readily modulated in adult animals, including microglia activation and neuroinflammation. Several neurobehavioural, neurodegenerative, mental and metabolic disorders, including Parkinson disease, autism spectrum disorder, schizophrenia, Alzheimer's disease, depression and obesity, have been linked to the gut microbiota. This review focuses on the role of the microorganisms in the development and function of the CNS and the ENS, as well as their potential role in pathogenesis.

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Section: The Human Microbiotamentioning

confidence: 99%

Section: Microbial Signalling To the Cns And The Ensmentioning

confidence: 99%

The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

Heiss

Olofsson

2019

J Neuroendocrinology

Self Cite

202

131

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“…In more detailed mechanistic studies with germ-free mice lacking the bile acid sensing farnesoid X nuclear receptor, signaling effects of microbiota-derived secondary bile acids were proposed as a central metabolic hub that is responsible for the contribution of gut microbiota in the development of diet-induced obesity [36,37]. The so far identified microbiotadriven mechanisms, contributing to obesity by modulating host energy balance, were recently reviewed [38]. Since obesity represents a major risk factor for the development of cardiometabolic disease states, it is essential to understand how the gut microbial ecosystem is influenced by nutrition and how this may impact host pathophysiology.…”

Section: In Utero (Me Af Pl)mentioning

confidence: 99%

“…Overnutrition and high-fat diet are recent environmental challenges and major risk factors, which dramatically increase the burden of obesity and related CVD risk [61]. It is meanwhile well-established that obesity results in dysbiosis of the commensal gut microbiota [38,62], an environmental factor contributing to diet-induced obesity [63]. Consequently, the intestinal microbiome profile is presently emerging as a novel factor associated with lifetime CVD risk [64].…”

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confidence: 99%

The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease

2018

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Commensal gut microbiota have recently been implicated in cardiovascular disease (CVD) and cerebrovascular disease. Atherosclerotic plaque formation depends on the colonization status of the host. In addition to host nutrition and the related microbiota-dependent metabolic changes, activation of innate immune pathways triggers the development of atherosclerosis and supports arterial thrombosis. Gnotobiotic mouse models have uncovered that activation of Toll-like receptor-2 by gut microbial ligands supports von Willebrand factor-integrin mediated platelet deposition to the site of vascular injury. Depending on nutritional factors, the microbiota-derived choline-metabolite trimethylamine Noxide (TMAO) increases atherosclerotic plaque size, triggers prothrombotic platelet function and promotes arterial thrombus growth. Hence, the composition of the commensal microbiota is an emerging risk factor for CVD. Here, we provide an overview on microbiota-dependent pathomechanisms that drive the development of CVD and arterial thrombosis.Keywords: Arterial thrombosis r Atherosclerosis r Cardiovascular disease r Microbiota r Toll-like receptors IntroductionAt birth, our body surfaces are colonized by microbial communities (microbiota), representing one of the most densely colonized microbial ecosystems [1]. This process is strongly influenced by genetic, nutritional, and environmental factors [2]. The commensal microbiota constitutes a permanent inflammatory stimulus [3], which is kept in check by the host's immune responses [4]. The microbiota can be viewed as an organ that impacts host physiology [5,6]. Changes in gut microbiota composition were associated with intestinal diseases (e.g. inflammatory bowel disease, colon cancer) and cardiometabolic disease states, such as diet-induced obesity, type 2 diabetes, atherosclerosis, and arterial thrombosis [7]. The results from recent experimental and clinical studies have led to the assumption that Correspondence: Christoph Reinhardt e-mail: Christoph.Reinhardt@unimedizin-mainz.de molecules synthesized by the intestinal microbiota are involved in the development of cardiovascular disease (CVD) [8] and may increase the risk of arterial thrombosis [9, 10] as well as the outcome of ischemic stroke [11]. Experimental evidence from germ-free mouse studies and metagenomics analyses have associated the gut microbiota with obesity [12][13][14][15], type 2 diabetes [3, 16, 17], stroke [11, 18], and CVD [8, 9, 19]. Therefore, targeting the composition and metabolic function of the intestinal microbiota may represent a therapeutic option that in the future may allow prevention and treatment of cardiometabolic diseases [20].Here, we provide a comprehensive overview on the emerging link between gut microbiota and CVD. We delineate the contribution of this complex microbial ecosystem to metabolic inflammation and its impact on host metabolism. The main focus of this review is to highlight how gut microbiota may contribute to the development of CVD, cerebrovascular disease and arterial thromb...

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“…In recent years, it has become more and more apparent that the normal microbiota is important for our health. There is apparently a delicate balance since the microbiota is connected both to modulation of the metabolism and development of neurodegenerative disease [13, 14]. It is very likely that the microbiota will be a common therapeutic target in the future.…”

mentioning

confidence: 99%