Engineered probiotics modulate the endocannabinoid system

Hwang, In Sung; Kim, Hye Rim; Sotto, Ryan De; Chang, Matthew Wook

doi:10.1016/j.biotno.2021.08.001

Cited by 10 publications

(11 citation statements)

References 33 publications

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“…inversely correlate to Faecalibacterium genus (Ding et al, 2020), and a further confirmation of the increase of butyrate faecal level in children with ASD has been previously reported (Wang et al, 2012). Recently, it has been provided evidence that gut microbial metabolites, and specifically butyrate, can directly modulate the eCB tone at gut epithelial level (Hwang et al, 2021). Using different concentrations, the study showed that both eCBs synthetizing enzymes (i.e., NAPE-PLD and DAGL) were reduced by butyrate treatment in dosedependent manner, and that in parallel butyrate was able to upregulate MAGL (but not FAAH) expression in the gut epithelial cells (Hwang et al, 2021).…”

Section: Asd and The Ecb Signaling-gut Microbiota Reciprocal Influencesupporting

confidence: 66%

“…Recently, it has been provided evidence that gut microbial metabolites, and specifically butyrate, can directly modulate the eCB tone at gut epithelial level (Hwang et al, 2021). Using different concentrations, the study showed that both eCBs synthetizing enzymes (i.e., NAPE-PLD and DAGL) were reduced by butyrate treatment in dosedependent manner, and that in parallel butyrate was able to upregulate MAGL (but not FAAH) expression in the gut epithelial cells (Hwang et al, 2021). Accordingly, it seems conceivable that an excessive increase of butyrate level in children with ASD (Wang et al, 2012;Coretti et al, 2018) could contribute to reduce both AEA and 2-AG synthesis and, in particular, cause a depletion of 2-AG tone in the gut epithelium.…”

Section: Asd and The Ecb Signaling-gut Microbiota Reciprocal Influencementioning

confidence: 99%

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The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders

2022

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The latest years have witnessed a growing interest towards the relationship between neuropsychiatric disease in children with autism spectrum disorders (ASD) and severe alterations in gut microbiota composition. In parallel, an increasing literature has focused the attention towards the association between derangement of the endocannabinoids machinery and some mechanisms and symptoms identified in ASD pathophysiology, such as alteration of neural development, immune system dysfunction, defective social interaction and stereotypic behavior. In this narrative review, we put together the vast ground of endocannabinoids and their partnership with gut microbiota, pursuing the hypothesis that the crosstalk between these two complex homeostatic systems (bioactive lipid mediators, receptors, biosynthetic and hydrolytic enzymes and the entire bacterial gut ecosystem, signaling molecules, metabolites and short chain fatty acids) may disclose new ideas and functional connections for the development of synergic treatments combining “gut-therapy,” nutritional intervention and pharmacological approaches. The two separate domains of the literature have been examined looking for all the plausible (and so far known) overlapping points, describing the mutual changes induced by acting either on the endocannabinoid system or on gut bacteria population and their relevance for the understanding of ASD pathophysiology. Both human pathology and symptoms relief in ASD subjects, as well as multiple ASD-like animal models, have been taken into consideration in order to provide evidence of the relevance of the endocannabinoids-microbiota crosstalk in this major neurodevelopmental disorder.

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Section: Asd and The Ecb Signaling-gut Microbiota Reciprocal Influencesupporting

confidence: 66%

Section: Asd and The Ecb Signaling-gut Microbiota Reciprocal Influencementioning

confidence: 99%

The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders

2022

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“…The total RNA of the co-cultured Caco-2 cells was extracted using a Trizol reagent (Hwang et al, 2021). RT-PCR was then performed to analyze the transcription levels of IL-6, IL-8, LL-37, SA1009, CCL20, and hBD-3 using the 2 −ΔΔCT method.…”

Section: Methodsmentioning

confidence: 99%

Engineering of a probiotic yeast for the production and secretion of medium-chain fatty acids antagonistic to an opportunistic pathogen Candida albicans

Ling

Liu

Sam

et al. 2023

Front. Bioeng. Biotechnol.

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Candida albicans is an opportunistic pathogen, with its infection as one of the causes of morbidity or mortality. Notably, the probiotic yeast Saccharomyces cerevisiae var. boulardii has shown the potential to fight against Candida infections. In this study, we aimed to engineer a commercial boulardii strain to produce medium-chain fatty acids (MCFAs) with antagonistic effects against C. albicans. First, we identified and characterized a boulardii strain and created its auxotrophic strain Δura3. Next, we constructed and expressed a heterologous MCFA biosynthetic pathway under the control of inducible and constitutive promoters. Aside from examining MCFA production and secretion, we confirmed MCFAs’ effects on C. albicans’ anti-biofilm and anti-hyphal formations and the immunomodulatory effect of MCFA-containing supernatants on Caco-2 cells. We found that under constitutive promoters, the engineered boulardii strain constitutively produced and secreted a mixture of C6:0, C8:0, and C10:0. The secreted MCFAs then reduced biofilm and hyphal formations in C. albicans SC5314. We also confirmed that MCFAs upregulated the expression of virulence-related genes in SC5314. Furthermore, we found that the constitutively produced MCFAs in the supernatant induced the upregulation of immune response genes in Caco-2 cells co-cultured with SC5314, indicating MCFAs’ roles in immunomodulation. Overall, the engineered boulardii strain produced and secreted MCFAs, as well as demonstrated antagonistic effects against C. albicans SC5314 and immune-modulatory effects in Caco-2. To our knowledge, this represents the first study tackling the metabolic engineering of a commercial probiotic yeast strain to constitutively produce and secrete MCFAs showing anti-Candida effects. Our study forms the basis of the potential development of a live biotherapeutics probiotic yeast against Candida infections through metabolic engineering strategies.

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“…334 EcN has also been engineered to produce 0.5−1 g/L butyrate in vitro but has yet to be evaluated in in vivo models. 335,336 Extracellular adenosine triphosphate (eATP) is an IBDassociated metabolite produced by activated immune cells and the gut microbiome. eATP is known to promote proinflammatory cytokine production and neuron apoptosis, as well as to suppress anti-inflammatory responses.…”

Section: Microbiome Metabolite Modulation Bymentioning

confidence: 99%

“…In addition to the decrease of Firmicutes and increase in Bacteroidetes, analysis of the metabolic pathways of the gut microbiome revealed a significant enhancement of the genes involved in carbohydrate, amino acid, vitamins, and energy metabolism . EcN has also been engineered to produce 0.5–1 g/L butyrate in vitro but has yet to be evaluated in in vivo models. , …”

Section: Strategies To Engineer the Microbiome For Therapeutic Applic...mentioning

confidence: 99%

Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies

et al. 2022

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The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.

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Engineered probiotics modulate the endocannabinoid system

Cited by 10 publications

References 33 publications

The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders

The Endocannabinoids-Microbiota Partnership in Gut-Brain Axis Homeostasis: Implications for Autism Spectrum Disorders

Engineering of a probiotic yeast for the production and secretion of medium-chain fatty acids antagonistic to an opportunistic pathogen Candida albicans

Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies

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