Metabolic engineering of human gut microbiome: Recent developments and future perspectives

Li, Peishun; Roos, Stefan; Luo, Hao; Ji, Boyang; Nielsen, Jens

doi:10.1016/j.ymben.2023.06.006

Cited by 11 publications

(3 citation statements)

References 107 publications

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“…On the contrary, despite the advantages and the embedded challenges, using this technology for gene editing in GEMs might bring risks and devastating consequences on the enteric prokaryotic inhabitants and the entire human genome [ 125 ]. Genetically engineered probiotics or synthetic microbial consortia should be regulated as drugs, not as less-controlled food supplements [ 126 ]. Their gut delivery could bring unexpected consequences, causing biosafety problems that should be addressed and overcome by regulatory authorities.…”

Section: The New Gems Can Change the Long-term Natural Evolution Of T...mentioning

confidence: 99%

The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health

Lerner,

Benzvi,

Vojdani

2024

Microorganisms

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Gut luminal dysbiosis and pathobiosis result in compositional and biodiversified alterations in the microbial and host co-metabolites. The primary mechanism of bacterial evolution is horizontal gene transfer (HGT), and the acquisition of new traits can be achieved through the exchange of mobile genetic elements (MGEs). Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by the GEMs’ horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on the human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to August 2023 using appropriate MeSH entry terms was performed. The GEMs’ horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cell inhabitants. The worldwide regulatory authority’s safety control of GEMs is not enough to protect public health. Viability, biocontainment, and many other aspects are only partially controlled and harmful consequences for public health should be avoided. It is important to remember that prevention is the most cost-effective strategy and primum non nocere should be the focus.

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Section: The New Gems Can Change the Long-term Natural Evolution Of T...mentioning

confidence: 99%

The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health

Lerner,

Benzvi,

Vojdani

2024

Microorganisms

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“…Additionally, the future development of gut-intervention therapies may involve the use of microbial-based therapeutics. This includes the development of engineered probiotics or microbial consortia that can deliver specific therapeutic functions to the gut[ 52 , 53 ]. For example, scientists are exploring the use of genetically modified probiotic strains that can produce beneficial metabolites or modulate the host immune response.…”

Section: The Future Of Gut-intervention Therapies For T2dmmentioning

confidence: 99%

Gut-targeted therapies for type 2 diabetes mellitus: A review

Xu,

Liu,

et al. 2024

World J Clin Cases

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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. The global prevalence of T2DM has reached epidemic proportions, affecting approximately 463 million adults worldwide in 2019. Current treatments for T2DM include lifestyle modifications, oral antidiabetic agents, and insulin therapy. However, these therapies may carry side effects and fail to achieve optimal glycemic control in some patients. Therefore, there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM. The gut microbiota, which refers to the community of microorganisms that inhabit the human gut, has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity. Alterations in gut microbiota composition and diversity have been observed in T2DM patients, with a reduction in beneficial bacteria and an increase in pathogenic bacteria. This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function. Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM. One potential approach is the use of probiotics, which are live microorganisms that confer health benefits to the host when administered in adequate amounts. Several randomized controlled trials have demonstrated that certain probiotics, such as Lactobacillus and Bifidobacterium species, can improve glycemic control and insulin sensitivity in T2DM patients. Mechanisms may include the production of short-chain fatty acids, the improvement of gut barrier function, and the reduction of inflammation. Another gut-targeted therapy is fecal microbiota transplantation (FMT), which involves the transfer of fecal material from a healthy donor to a recipient. FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM. A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity. However, FMT carries potential risks, including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable. In addition to probiotics and FMT, other gut-targeted therapies are being investigated for the management of T2DM, such as prebiotics, synbiotics, and postbiotics. Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria, while synbiotics combine probiotics and prebiotics. Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host. The NIH SPARC program, or the Stimulating Peripheral Activity to Relieve Conditions, is a research initiative aimed at developing new therapies for a variety of health conditions, including T2DM. The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs, in order to regulate glucose levels in the body. The goal of this approach is to develop targeted, non-invasive therapies that can help patients better manage their diabetes. One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve, which plays an important role in regulating glucose metabolism. Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM. Gut-targeted therapies, such as probiotics and FMT, have shown potential for improving glycemic control and insulin sensitivity in T2DM patients. However, further research is needed to determine the optimal dose, duration, and safety of these therapies.

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“…Increasingly, metabolic modeling is being employed to investigate the dynamics of microbial communities due to the advantages of in silico analysis over complex in vivo analyses of bacterial communities. The application of metabolic modeling approaches in engineering communities has been reviewed elsewhere [43], along with suggested strategies and available tools [44][45][46]. Utilizing GEMs, the metabolic functions of the human gut microbiome have been effectively investigated.…”

Section: Digestion and Essential Nutrient Provisionmentioning

confidence: 99%

Engineering Gut Symbionts: A Way to Promote Bee Growth?

Sattayawat,

Inwongwan,

Noirungsee

et al. 2024

Insects

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Bees play a crucial role as pollinators, contributing significantly to ecosystems. However, the honeybee population faces challenges such as global warming, pesticide use, and pathogenic microorganisms. Promoting bee growth using several approaches is therefore crucial for maintaining their roles. To this end, the bacterial microbiota is well-known for its native role in supporting bee growth in several respects. Maximizing the capabilities of these microorganisms holds the theoretical potential to promote the growth of bees. Recent advancements have made it feasible to achieve this enhancement through the application of genetic engineering. In this review, we present the roles of gut symbionts in promoting bee growth and collectively summarize the engineering approaches that would be needed for future applications. Particularly, as the engineering of bee gut symbionts has not been advanced, the dominant gut symbiotic bacteria Snodgrassella alvi and Gilliamella apicola are the main focus of the paper, along with other dominant species. Moreover, we propose engineering strategies that will allow for the improvement in bee growth with listed gene targets for modification to further encourage the use of engineered gut symbionts to promote bee growth.

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Metabolic engineering of human gut microbiome: Recent developments and future perspectives

Cited by 11 publications

References 107 publications

The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health

The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health

Gut-targeted therapies for type 2 diabetes mellitus: A review

Engineering Gut Symbionts: A Way to Promote Bee Growth?

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