Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose–response effects on glucose metabolism in human subjects with metabolic syndrome

Gilijamse, Pim W.; Hartstra, Annick V.; Levin, Evgeni; Wortelboer, Koen; Serlie, Mireille J.; Ackermans, Mariëtte T.; Herrema, Hilde; Nederveen, Aart J.; Imangaliyev, Sultan; Aalvink, Steven; Sommer, Morten Otto Alexander; Levels, Han; Stroes, Erik S.G.; Groen, Albert K.; Kemper, E. Marleen; Vos, Willem M. de; Nieuwdorp, Max; Prodan, Andrei

doi:10.1038/s41522-020-0127-0

Cited by 58 publications

(76 citation statements)

References 36 publications

(71 reference statements)

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“…Probiotics containing SCFA-producing microbes including Bifidobacterium , Enterococcus , and Lactobacillus were suggested to have a variety of health benefits including anti-inflammatory and beneficial metabolic effects [ 158 ]. In addition, oral treatment with specific Bifidobacterium , Lactobacillus , and SCFA-producing Anaerobutyricum soehngenii species had modest blood pressure lowering effects in humans [ 43 , 159 ]. However, our understanding of mechanisms is based on animal research.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Gut Microbiota in Hypertension and Atherosclerosis: A Review

et al. 2020

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Gut microbiota and its metabolites such as short chain fatty acids (SCFA), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO) impact cardiovascular health. In this review, we discuss how gut microbiota and gut metabolites can affect hypertension and atherosclerosis. Hypertensive patients were shown to have lower alpha diversity, lower abundance of SCFA-producing microbiota, and higher abundance of gram-negative bacteria, which are a source of LPS. Animal studies point towards a direct role for SCFAs in blood pressure regulation and show that LPS has pro-inflammatory effects. Translocation of LPS into the systemic circulation is a consequence of increased gut permeability. Atherosclerosis, a multifactorial disease, is influenced by the gut microbiota through multiple pathways. Many studies have focused on the pro-atherogenic role of TMAO, however, it is not clear if this is a causal factor. In addition, gut microbiota play a key role in bile acid metabolism and some interventions targeting bile acid receptors tend to decrease atherosclerosis. Concluding, gut microbiota affect hypertension and atherosclerosis through many pathways, providing a wide range of potential therapeutic targets. Challenges ahead include translation of findings and mechanisms to humans and development of therapeutic interventions that target cardiovascular risk by modulation of gut microbes and metabolites.

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Section: Therapeutic Strategiesmentioning

confidence: 99%

Gut Microbiota in Hypertension and Atherosclerosis: A Review

et al. 2020

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“…For example, in one study the butyrogenic strain Anaerobutyricum soehngenii was identified to positively correlate with improved insulin sensitivity after FMT [ 18 ]. In a recently published phase I/II trial in humans with the metabolic syndrome, supplementation with A. soehngenii was shown to be safe and to improve insulin sensitivity after 4 weeks of daily treatment [ 130 ]. Although no effect on faecal SCFA levels was observed in the given setting, trials like these will open up more treatment opportunities using microbial metabolites.…”

Section: Possible Interventionsmentioning

confidence: 99%

Intestinal microbial metabolites in human metabolism and type 2 diabetes

Herrema

Niess

2020

Diabetologia

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Humans with the metabolic syndrome and type 2 diabetes have an altered gut microbiome. Emerging evidence indicates that it is not only the microorganisms and their structural components, but also their metabolites that influences the host and contributes to the development of the metabolic syndrome and type 2 diabetes. Here, we discuss some of the mechanisms underlying how microbial metabolites are recognised by the host or are further processed endogenously in the context of type 2 diabetes. We discuss the possibility that gut-derived microbial metabolites fuel the development of the metabolic syndrome and type 2 diabetes.

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“…Due to significant interest in development of defined bacterial therapeutics for human health applications 31 and the beneficial role of butyrate produced by gut microbiota on a myriad of health outcomes [17][18][19][20][21][22][23][24][25]32 , we sought to apply our modeling framework to understand how community composition impacts butyrate production in synthetic communities of prevalent and diverse human gut microbes. Butyrate production is a specialized function of a subset of species in the gut (~10-25% of microbial genomes are predicted to harbor this pathway in healthy individuals 33 ).…”

Section: Resultsmentioning

confidence: 99%

Design of synthetic human gut microbiome assembly and function

Clark

Connors

Stevenson

et al. 2020

Preprint

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The assembly of microbial communities and functions emerge from a complex and dynamic web of interactions. A major challenge in microbiome engineering is identifying organism configurations with community-level behaviors that achieve a desired function. The number of possible subcommunities scales exponentially with the number of species in a system, creating a vast experimental design space that is challenging to even sparsely traverse. We develop a model-guided experimental design framework for microbial communities and apply this method to explore the functional landscape of the health-relevant metabolite butyrate using a 25-member synthetic human gut microbiome community. Based on limited experimental measurements, our model accurately forecasts community assembly and butyrate production at every possible level of complexity. Our results elucidate key ecological and molecular mechanisms driving butyrate production including inter-species interactions, pH and hydrogen sulfide. Our model-guided iterative approach provides a flexible framework for understanding and predicting community functions for a broad range of applications.

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Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose–response effects on glucose metabolism in human subjects with metabolic syndrome

Cited by 58 publications

References 36 publications

Gut Microbiota in Hypertension and Atherosclerosis: A Review

Gut Microbiota in Hypertension and Atherosclerosis: A Review

Intestinal microbial metabolites in human metabolism and type 2 diabetes

Design of synthetic human gut microbiome assembly and function

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