Engineered Akkermansia muciniphila: A promising agent against diseases (Review)
- Authors:
- Published online on: October 29, 2020 https://doi.org/10.3892/etm.2020.9415
- Article Number: 285
-
Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
1. Introduction
With increasing economic development, chronic non-communicable diseases have emerged as a substantial global concern due to common risk factors, such as unhealthy diets and environmental pollution (1,2). Although a range of pharmacological and surgical interventions are constantly being devised to address the increased numbers of cases of non-communicable diseases, the side effects and contraindications of certain medicines or radiotherapy have limited the number of patients that are able to receive such treatments (3,4). Furthermore, the unavoidable postoperative complications such as surgical site infection, abscess, active bleeding, hematoma and anastomotic leak, resulting from surgery may worsen a patient's state (5). Therefore, researchers have begun to consider other possibilities to cope with this global problem (6,7). The term dysbiosis refers to the major changes in the gut microbial ecosystems that contribute to a range of metabolic disorders, including obesity, type 1 and type 2 diabetes and inflammatory bowel disease (8-11). Numerous other types of disease like autism or allergies have also been associated with an imbalance in gut microflora composition (12,13). Several strategies to normalize human gut microbial ecosystems are available to treat different syndromes, including fecal microbiota transplantation, which has demonstrated promising results (14). At present, probiotics are commonly used to improve the intestinal environment (15-17).
To further determine the relationship between the gut microflora and a healthy human state, the use of metagenomics and metatranscriptomic sequencing techniques has been proven to provide a compositional snapshot of the microbial species in the gut, as well as to sequence their expressed genes (18,19). With the elucidated genetic background of different gut microflora, it also provides a wide range of possibilities to modulate the gut microflora composition genetically for greater therapy. Advances in synthetic biology have extended this therapeutic potential, as selected bacteria can be tailored to deliver drugs or molecules to act directly on the host (20). An increasing abundance of human-associated bacteria have been identified to provide health benefits, including Lactococcus lactis (L. lactis), Escherichia coli (E. coli) and Bifidobacterium, making them desirable engineering targets for therapeutic application (21-27). Similar efforts may also be applied to Akkermansia muciniphila (A. muciniphila), a microbial species that has been proposed as a novel candidate for probiotic therapy (28). In the present review paper, the potential of A. muciniphila as an engineered bacterium was discussed by first reviewing other engineered bacteria. The review covered its colonization sites in human intestines, therapeutic effects and probiotic characteristics, prior to identifying potential avenues for modification.
2. Commonly engineered bacteria used for the treatment of diseases
The most commonly engineered bacteria provide a platform to develop probiotics as a novel direction in therapeutic studies. In the following sections, some of these cases are discussed in further detail. By noting similarities in their therapeutic effects, characterization status and the strategies used for their modification, the current review aimed to demonstrate why A. muciniphila is being considered for similar engineering approaches.
E. coli. E. coli is an inhabitant of the human gastrointestinal tract; its well-characterized genome, accessible and versatile plasmid vector, susceptibility to genetic manipulation and high recombinant protein synthesis rates renders it one of the most desirable hosts for the expression of recombinant proteins (29,30). Since recombinant human insulin was first produced in E. coli by Genentech in 1978, numerous genetic engineering strategies have been developed for E. coli, providing a genetic circuit model for the subsequent genetic manipulation of bacteria (31). For example, by deleting the arginine repressor gene of E. coli Nissle (EcN) and integrating a feedback-resistant arginine synthase into the intergenic region controlled by the fnrS promoter, Kurtz et al (24) generated the SYNB1020 clinical candidate for the treatment of hyperammonemia. In addition, Whelan et al (32) ligated a functional nematode gene into the pMu13 plasmid and transformed it into EcN; in the EcN, the expressed nematode cystatin, reported to have anti-inflammatory properties, decreased the inflammatory monocyte/macrophage migration and positively affected the epithelial barrier function in both mice and piglets. The introduced genetic material was able to overcome the defense barrier of the host cell and was stably maintained as a plasmid with the aid of selectable markers and a compatible origin of replication, or by integration into the genome (24).
Lactobacillus (LAB)
LAB is a commensal intestinal microbiota species with widespread use in the production of fermented foods (33,34). By virtue of its numerous health-promoting effects in humans and its decoded genetic sequence, LAB has become one of the most convincing engineered probiotics (35-37). In 2015, Yang et al (27) constructed the recombinant strain LAB plantarum (L. plantarum) NC8, which expresses angiotensin-converting enzyme inhibitory peptides (ACEIPs) for prolonging antihypertensive effects; the recombinant expression vector pSIP409-ACEIP was built by replacing the gusA gene in the pSIP409 plasmid with genes encoding ACEIPs. Through incubating its DNA with available methyltransferases in vitro to match the host's DNA methylation patterns, the transformation efficiency of L. plantarum was raised to a level comparable with that of E. coli. This vector was subsequently transformed into L. plantarum NC8. An antihypertensive effect was noted following the oral administration of the engineered strain to spontaneously hypertensive rats, as evidenced by a reduction in abnormal systolic blood pressure and in triglyceride, endothelin and angiotensin II levels. For further consideration, the expression levels of the integrated genes should be monitored and regulated (38).
Different promoter-repressor systems have been constructed for the induction of recombinant protein expression in L. plantarum to evaluate their stability and efficiency (39). An increasing number of systems have emerged, such as the quorum-sensing system, chemical-based induction system and temperature-sensitive system, which enhanced the abilities of microbes to sense, respond to and record their local environment, as well as improving the ability to evaluate and control the expression levels of the desired genes, which are designed to produce the required product (40-42).
Bifidobacterium
Of all the commensal bacteria inhabitants in the mammalian gut, bacteria of the Bifidobacterium genus represent some of the most prevalent probiotic species, which have been used to prevent or treat colorectal cancer, diarrhea, necrotizing enterocolitis and IBD (43-48) In view of these prominent therapeutic characteristics, molecular genetic studies are of crucial importance. Among the Bifidobacterium genus, Bifidobacterium longum (B. longum) was identified to exert more significant positive effects on the gut environment compared with others (49). The complete genome sequence of this strain has been deciphered and it frequently used in genetic manipulation. As it was discovered to selectively grow in the hypoxic regions of solid tumours, genetic modifications to B. longum for cancer therapy have been proposed (45). In a previous study, the tumstatin gene was inserted into a plasmid and electrically transformed into the B. longum NCC2705 strain, which generated an anticancer effect in tumor-bearing mice by inhibiting the apoptotic vascular endothelial cells of the transplanted tumours (50). A similar strategy was employed in other B. longum strains, enabling them to express more anticancer drugs (51-53). These achievements demonstrate the strength and utility of engaging the immune system at the level of the intestinal mucosa using ingested microbes.
Commonly engineered pathogens
Foodborne pathogens, such as Salmonella typhimurium (S. typhimurium) and Listeria monocytogenes (L. monocytogenes), have also been engineered using an attenuation operation for therapeutic purposes (54). Examples of attenuation strategies include interrupting the transport of lipids, purines and/or metabolites (54). A previous study developed an attenuated S. typhimurium strain, VNP20009 DNase I, which contained defective adenine and lipopolysaccharide metabolism genes, and a plasmid with a humanized toxin DNase I sequence inserted; the results indicated that the combination of VNP20009 DNase I and triptolide significantly reduced tumor volume, prolonging the survival of mice (55). A similar strategy has been adopted for modifying the L. monocytogenes strain for use as a vaccine for different types of disease; for instance, the administration of the Lmdd-multiple peptide fusing genes (MPFG) strain, which was based on a vaccine against hepatocellular carcinoma (HCC) (56), created an antitumor response towards the human leukocyte antigen (HLA) epitopes of MPFG (HLA-A0201), presenting a potentially feasible strategy for the prevention of HCC (57). Biocontainment and biosafety are crucial factors in the clinical application, to avoid the harm that engineered pathogens like S. typhimurium and L. monocytogenes cause, thus the attenuation of these strains to lower the expression levels of pernicious genes is a critical step. At present, to achieve greater control and safety, kill switches and genetic firewalls have been added into genetic circuits (58).
3. Next generation of engineered bacteria: A. munciphila Akkermansia
Overview of A. muciniphila
A. muciniphila was first isolated from a fecal sample in anaerobic medium containing gastric mucin (its sole energy source) in 2004 by Derrien et al (59). A. muciniphila was discovered to directly bind to enterocytes to enable colonization, while its degradation of mucin was identified to stimulate mucin production and increase mucin thickness, thereby strengthening epithelial integrity (60). In addition, metabolites, mainly short-chain fatty acids, produced by A. muciniphila were found to be absorbed in the colon and serve as an energy source for colonocytes, and they also exhibited potential therapeutic and anti-inflammatory effects in various types of metabolic disorder, such as obesity, IBD, and diabetes (61-63), as illustrated in Fig. 1. Moreover, the effects of some exposed active molecules of A. muciniphila have been demonstrated to remain after pasteurization; for instance, as Amuc_1100 is heat-stable, it is able to replicate almost all of the effects of live A. muciniphila or inactivate the inhibitory compounds for live A. muciniphila (64,65).
A. muciniphila in metabolic disorders and other types of disease. Obesity
Globally, the prevalence of excess weight between the years 1980 and 2013 has increased to 27.5% in adults and 47% in children, with 2.1 billion people in the world classifying as overweight (BMI >25 kg/m2) and over 500 million being classified as obese (BMI >30 kg/m2) (66). Obesity has become a worldwide health concern, with current medical and lifestyle interventions largely failing to offer adequate solutions. Increasing evidence has indicated that probiotics are involved in gut barrier maintenance and inflammation normalization, suggesting that their adoption could eventually result in a long-term treatment for obesity (67,68).
In recent years, A. muciniphila has been proposed as a potential probiotic for the treatment of obesity, as significantly decreased levels of A. muciniphila were observed in obese or overweight individuals (69,70). Everard et al (71) demonstrated that administering a daily dose of live A. muciniphila to mice with diet-induced obesity significantly lowered their body weight and sanguineous lipopolysaccharide levels (71). However, this treatment was reported to increase fat mass development and alter adipose tissue metabolism. Similarly, a study of overweight and obese insulin-resistant volunteers indicated that oral supplements coated with pasteurized A. muciniphila normalized the mean adipocyte diameter and lowered plasma leptin concentrations (72).
Type 2 diabetes
The prevalence of diabetes has increased in parallel with the global rise in obesity, with type 2 diabetes accounting for >90% of all cases of diabetes (73-75). Both obesity and type 2 diabetes have been associated with changes in nutrition and more sedentary lifestyles, thus adopting A. muciniphila interventions for the treatment of diabetes has been hypothesized to exert similar therapeutic implications (10,76). Previous studies reported that prediabetic patients and patients with type 2 diabetes had lower amounts of A. muciniphila in the gut compared with healthy individuals (77,78). The relationship between A. muciniphila and type 2 diabetes was also insinuated following metformin treatment, which induced high levels of A. muciniphila in a previous study (79). Notably, Depommier et al (72) observed more significant improvements to insulin sensitivity and reductions in insulinemia following the use of pasteurized, instead of live, A. muciniphila.
Atherosclerosis
Atherosclerosis is a pathological condition underlying adverse vascular events (80). Previous studies have identified that the gut microbiota contributes to atherosclerosis by controlling the direct invasion of the host, the activation of the innate and acquired immune system and alterations in metabolism. Thus, A. muciniphila has also been suggested for the treatment of atherosclerosis (81-83). Li et al (84) fed germ-free atherogenic mice lacking apolipoprotein E with A. muciniphila and revealed that the oral gavage of A. muciniphila significantly impeded atherosclerotic lesion growth by decreasing the intestinal permeability and inhibiting the proliferation and migration of macrophages; these effects persisted in spite of A. muciniphila pasteurization.
Autism-related gastrointestinal disturbances
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder in which gastrointestinal disturbances are commonly reported (85). Through the analysis of fecal samples, Wang et al (86) reported a decreased abundance of A. muciniphila in children with ASD and their siblings, as well as a thinner gastrointestinal mucus barrier compared with control subjects. Other previous studies have also indicated that intestinal barrier impairment was aggravated in children with ASD and their immediate relatives, suggesting that A. muciniphila may guide the implementation of dietary interventions to reduce gut permeability in individuals with ASD.
Other diseases
In the majority of the studies discussed, when supplied in a viable form, therapeutic effects of A. muciniphila were noted for metabolic disorders. However, such treatment could also extend to other diseases. For example, in cancer treatment, A. muciniphila employment was suggested to enhance the effects of immunotherapy (87,88). The fecal matter of patients with cancer with positive responses to immunotherapy has been studied for A. muciniphila, as an abundance of the bacteria can reflect the state of immunotherapy (87). In addition, A. muciniphila was also reported to exhibit protective effects in immune-mediated diseases, including atopic diseases, IBD and liver damage (65,89,90). The association between A. muciniphila and immune-mediated diseases was explained using whole transcriptome analysis of intestinal tissue samples, which indicated that A. muciniphila regulated the expression of the majority of the genes associated with immune responses (90-94).
Evidence for the viability of engineered A. muciniphila
The advent of next-generation sequencing and whole-genome sequencing has provided additional scope for more bacteria to be genetically modified. Based on this, the prospects for engineering A. muciniphila are promising.
The genome of A. muciniphila BAA-835 was first sequenced in 2011, from which A. muciniphila was predicted to synthesize all 20 canonical amino acids, as well as important cofactors and vitamins (95). In 2015, genes from the A. muciniphila strain Urmite were assigned to strain ATCC BAA-835, suggesting that the majority of these genes were involved in metabolic reactions (96). Recently, 39 new A. muciniphila strains were sequenced and analyzed, with several gene flow and recombination events being noted, indicating the development of a feasible background for future genetic engineering studies (97).
Moreover, an efficient and scalable workflow for the cultivation and preservation of A. muciniphila cells has been developed, resulting in viable Akkermansia colonies with high yields and very high stability, as well as up to 97.9±4.5% survival of >1 year when stored in glycerol-amended medium at -80˚C (98). The growth of A. muciniphila can be monitored and controlled by various quality assessment and control procedures to ensure that viable cells of A. muciniphila are available. In addition, although A. muciniphila is an anaerobic bacterium, it has demonstrated an ability tolerate and even benefit from nanomolar concentrations of oxygen in liquid medium (99). These properties extend the possibility of A. muciniphila to be manipulated for engineering (Fig. 1).
Potential genome editing tools for engineering A. munciphila
In general, plasmids are the first tool considered when genome editing is required. Plasmids contain appropriate DNA as the bacterial origin of replication, an antibiotic resistance cassette and the gene of interest, which is transcribed from a prokaryotic promoter (100,101). Adequate expression of the therapeutic gene or genes is ensured by using appropriate promoters and other regulatory elements (100,101). In previous years, the genetic toolbox of plasmids has been greatly expanded by adding sensors, regulators, memory circuits, delivery devices and kill switches (102). Once the recombinant plasmid carrying the desired gene tracks down signal molecules secreted by target cells or tissues, it releases therapeutics locally, and is subsequently self-digested as programmed to avoid any infection (103,104). After construction, plasmids are converted to the hosts by chemical, mechanical or physical techniques, with mammalian cell ‘poration’ systems (electroporation and sonoporation) being the most important and common techniques used (105-107).
In addition, extra genome integration in a chromosome of the host cell has been discovered to support the development of engineered bacteria (108). Normally, a designed homologous single-stranded DNA donor is provided based on the introduction of a site-specific double-strand DNA break (DSB) into the locus of interest (109). Information encoded on this template can be used to repair the DSB, resulting in the addition of the desired gene at the site of the break (109). Recombination systems carried by helper plasmids are crucial during this process (109-112). In the following sections, several mature recombination systems developed in LAB or E. coli are described, which could be applied to A. muciniphila once limitations relating to species differences have been eliminated.
Nisin-controlled gene expression (NICE) system
The NICE system is one of the most widely used tools for chromosomal integration exploited for engineering Lactobacillus. It is constructed for gene expression based on nisA and nisF promoters via a two-component regulatory system consisting of the histidine protein kinase, nisK, and the response regulator, nisR (113-116). When a gene of interest is placed behind the inducible promoter, PnisA, on a plasmid and transformed into a nisRK strain, the expression of the cloned gene can be activated by the addition of nisin (Fig. 2). Using the dual plasmid system, the classic NICE system can be successfully introduced into the majority of bacteria. For example, Mohseni et al (117) genetically engineered L. lactis using a NICE system with pNZ8148 to express the native and codon-optimized recombinant E7 [E7 is a good candidate protein for vaccine development against human papillomavirus (HPV)-related cervical cancer] oncogenes isolated from HPV; the results for the overall production of E7 by L. lactis NZ9000 containing codon-optimized E7 was >2.7-fold higher compared with NZ9000 containing the native E7 strain. The findings also indicated that the amount of recombinant E7 oncoprotein accumulation depended on the concentration of nisin added, with the highest concentration achieved in the presence of 10 ng/ml nisin for both recombinant L. lactis strains. However, the exposed drawback of the system was that its basal expression was leaky; therefore, it may not applicable for production of the desired proteins or for the expression of toxic proteins (118).
λ recombination system
The bacteriophage λ Red homologous recombination system has been studied over the past 50 years as a model system for the transfer of chromosomal DNA from species (119). The λ recombination system, designated ‘Red,’ consists of two proteins; α, an exonuclease that acts on double-stranded (ds)DNA, and β, a single-stranded (ss)DNA binding protein capable of annealing complementary ssDNA strands (120). Red-mediated recombination is assisted by the γ protein, which increases α and β activity on linear dsDNA by inhibiting E. coli RecBCD exonuclease (121,122). In the past, NICE restricted the integration of molecular weight DNA into the host strain; however, the new lambda Red recombinase-mediated integration strategy was found to transform higher molecular weight DNA of variable lengths into any non-essential locus in the host chromosome (123). Juhas and Ajioka (124) successfully integrated 15 kB DNA encoding sucrose catabolism and lactose metabolism and transport operons into the flsu locus of the flagellar region 3b in the E. coli K12 MG1655 chromosome; this approach preferred the use of overlapping DNA fragments for integrating the high molecular weight DNA. Elongation of the integrated DNA sequence is facilitated by the alternative use of kan and cat-yfp cassettes tagged in different DNA fragments, which is less time-consuming compared with the standard lambda Red recombinase-mediated integration (124). Under monitoring, this new strategy did not reveal any negative effects on the host strain. However, compared with E. coli, to the best of our knowledge, there are fewer reports regarding the use of this technique on other strains.
CRISPR-Cas system
In the CRISPR-Cas system, the small CRISPR RNAs encoded by CRISPR spacer sequences form a duplex with a trans-activating CRISPR RNA. The duplex with the Cas9 protein subsequently searches the presented DNA for a Cas-specific sequence (Fig. 3) (125-127). Upon recognition of the specific sequence, Cas9 induces the targeted DSB, enabling the modification of a target gene sequence through host bacterial DNA repairing systems (128,129). The presence of a homologous template ensures the insertion of the addition in the region of the DSB. CRISPR-based technologies have been implemented for E. coli, Streptococcus pneumoniae, L. lactis and probiotic LAB species for the production of pharmaceutical products and precursors of high industrial significance (130-132). Various types of CRISPR are currently used for producing desired strains with therapeutic potentials. Δ-integration CRISPR enables strains to have multiple loci chromosomal integration, whereas CRISPR-based homology-directed repair allows site-specific integration (133). A catalytically inactive form of Cas9 (dCas9), has been developed to direct the promoter or coding regions to prevent transcription rather than cleaving the DNA, known as CRISPR interference (78). This technique has been used to control gene expression in Corynebacterium glutamicum, in which it was employed to downregulate multiple genes by concatenating single guide RNA sequences encoded on one plasmid (134). Genomic sequencing of the A. muciniphila strain determined the CRISPR loci, suggesting that the A. muciniphila system initiates the CRISPR defensive mechanism frequently and can be modified using CRISPR-Cas9(95). An automated pipeline named CRISPR discovery has since been developed for the identification of CRISPR repeats and Cas genes in genome assemblies, to determine the type and subtype and to describe system completeness (135). With this knowledge, it is hypothesized that an endogenous CRISPR-Cas9 system can be developed for A. muciniphila, allowing it to avoid the host's immune system.
4. Conclusion
As illustrated in Fig. 1, A. muciniphila is a potential probiotic that binds to enterocytes for colonization, which can regulate the host's metabolism and immune response. It has been revealed to be a promising therapeutic for the treatment of obesity, type 2 diabetes, atherosclerosis, autism-related gastrointestinal disturbances and other types of disease (Fig. 1). Due to an increased understanding of how its genetics relate to its pathogenicity, as well as the techniques required for effective culturing and preservation, A. muciniphila is expected to find use as one of numerous engineered bacteria. The present review described the potential of A. muciniphila as an engineered bacterium for the modulation of metabolic pathways and the production of desired proteins of therapeutic value, with high yields (using promoters, enhancers and terminators), and introduced several mature recombination systems that could be used for its genetic modification. Based on the deployment of other strains used in the aforementioned procedures, it was suggested that ingested A. muciniphila may be programmed to interact with signals secreted within its environment and respond to information. Thus, it could be applied to treat metabolic imbalances, pathological conditions in tissues and to assist postoperative recovery. Apart from its use as a diagnostic tool, it is feasible that A. muciniphila may also be designed for site-specific delivery of therapeutic compounds based on genetic circuit modulation. In addition, given that A. muciniphila has the capability to inhibit regulatory pathways that control immune responses, it may also be remodeled for application in vaccinations. Takei et al (136) successfully modified B. longum to express full-length antibodies against chronic hepatitis C virus infections in a murine model, demonstrating the ability to engaging the immune system using engineered commensal microbes.
However, despite its encouraging prospects, further studies of engineered A. muciniphila are still required. Currently, engineered bacteria are more frequently applied in animal or preclinical models, thus further clinical trials are required to check their efficacy and risk ratio. These clinical trials should include the following: i) Several control groups using the same dosage of normal bacteria for comparison; ii) randomization and double blinding for causality; and iii) statistical analyses for significance (137). However, Lawenius et al (138) discovered that pasteurized A. muciniphila did not protect against ovariectomy-induced bone loss. Thus, A. muciniphila treatment may not be as good as initially expected.
Acknowledgements
Not applicable.
Funding
No funding was received.
Availability of data and materials
Not applicable.
Authors' contributions
TC conceived the idea for the review and designed its framework. YZ conducted the research and wrote the manuscript. Both authors edited the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
|
WHO and UNICEF. Health in the post-2015 development agenda report of the Global Thematic Consultation on Health. World We Want. 31:514–526. 2014. | |
|
Dora C, Haines A, Balbus J, Fletcher E, Adair-Rohani H, Alabaster G, Hossain R, de Onis M, Branca F and Neira M: Indicators linking health and sustainability in the post-2015 development agenda. Lancet. 385:380–391. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Novelli G, Biancolella M, Latini A, Spallone A, Borgiani P and Papaluca M: Precision medicine in non-communicable diseases. High-Throughput. 9(3)2020.PubMed/NCBI View Article : Google Scholar | |
|
Imaoka T, Nishimura M, Daino K, Takabatake M, Moriyama H, Nishimura Y, Morioka T, Shimada Y and Kakinuma S: Risk of second cancer after ion beam radiotherapy: Insights from animal carcinogenesis studies. Int J Radiat Biol. 95:1431–1440. 2019.PubMed/NCBI View Article : Google Scholar | |
|
O'Malley RB and Revels JW: Imaging of abdominal postoperative complications. Radiol Clin North Am. 58:73–91. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Suri S, Kumar V, Kumar S, Goyal A, Tanwar B and Kaur J and Kaur J: DASH dietary pattern: A treatment for non-communicable diseases. Curr Hypertens Rev. 16:108–114. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Zhu J, Yang J and Luo Y: Applications of engineered intestinal bacteria in disease diagnosis and treatment. Sheng Wu Gong Cheng Xue Bao. 35:2350–2366. 2019.PubMed/NCBI View Article : Google Scholar : (In Chinese). | |
|
Parséus A, Sommer N, Sommer F, Caesar R, Molinaro A, Ståhlman M, Greiner TU, Perkins R and Bäckhed F: Microbiota-induced obesity requires farnesoid X receptor. Gut. 66:429–437. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Kostic AD, Gevers D, Siljander H, Vatanen T, Hyötyläinen T, Hämäläinen AM, Peet A, Tillmann V, Pöhö P, Mattila I, et al: The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 17:260–273. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, et al: A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 490:55–60. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Zhang M, Sun K, Wu Y, Yang Y, Tso P and Wu Z: Interactions between intestinal microbiota and host immune response in inflammatory bowel disease. Front Immunol. 8(942)2017.PubMed/NCBI View Article : Google Scholar | |
|
Lu T, Chen Y, Guo Y, Sun J, Shen W, Yuan M, Zhang S, He P and Jiao X: Altered gut microbiota diversity and composition in chronic urticaria. Dis Markers. 2019(6417471)2019.PubMed/NCBI View Article : Google Scholar | |
|
Cryan JF, O'Riordan KJ, Sandhu K, Peterson V and Dinan TG: The gut microbiome in neurological disorders. Lancet Neurol. 19:179–194. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Jiménez-Avalos JA, Arrevillaga-Boni G, González-López L, García-Carvajal ZY and González-Avila M: Classical methods and perspectives for manipulating the human gut microbial ecosystem. Crit Rev Food Sci Nutr: Mar 2, 2020 (Epub ahead of print). doi: 10.1080/10408398.2020.1724075. | |
|
Szajewska H: What are the indications for using probiotics in children? Arch Dis Child. 101:398–403. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Chua KJ, Kwok WC, Aggarwal N, Sun T and Chang MW: Designer probiotics for the prevention and treatment of human diseases. Curr Opin Chem Biol. 40:8–16. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Sanders ME, Akkermans LMA, Haller D, Hammerman C, Heimbach J, Hörmannsperger G, Huys G, Levy DD, Lutgendorff F, Mack D, et al: Safety assessment of probiotics for human use. Gut Microbes. 1:164–185. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Khangwal I and Shukla P: Combinatory biotechnological intervention for gut microbiota. Appl Microbiol Biotechnol. 103:3615–3625. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Yadav M and Shukla P: Recent systems biology approaches for probiotics use in health aspects: A review. 3 Biotech. 9(448)2019.PubMed/NCBI View Article : Google Scholar | |
|
Kumar M, Yadav AK, Verma V, Singh B, Mal G, Nagpal R and Hemalatha R: Bioengineered probiotics as a new hope for health and diseases: An overview of potential and prospects. Future Microbiol. 11:585–600. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Yadav R, Singh PK and Shukla P: Metabolic engineering for probiotics and their genome-wide expression profiling. Curr Protein Pept Sci. 19:68–74. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W and Remaut E: Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science. 289:1352–1355. 2000.PubMed/NCBI View Article : Google Scholar | |
|
Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, van Deventer SJ, Neirynck S, Peppelenbosch MP and Steidler L: A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol. 4:754–759. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Kurtz CB, Millet YA, Puurunen MK, Perreault M, Charbonneau MR, Isabella VM, Kotula JW, Antipov E, Dagon Y, Denney WS, et al: An engineered E. Coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans. Sci Transl Med. 11(eaau7975)2019.PubMed/NCBI View Article : Google Scholar | |
|
Saltzman DA, Katsanis E, Heise CP, Hasz DE, Vigdorovich V, Kelly SM, Curtiss R III, Leonard AS and Anderson PM: Antitumor mechanisms of attenuated Salmonella typhimurium containing the gene for human interleukin-2: A novel antitumor agent? J Pediatr Surg. 32:301–306. 1997.PubMed/NCBI View Article : Google Scholar | |
|
Fang X, Tian P, Zhao X, Jiang C and Chen T: Neuroprotective effects of an engineered commensal bacterium in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Parkinson disease mouse model via producing glucagon-like peptide-1. J Neurochem. 160:441–452. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Yang G, Jiang Y, Yang W, Du F, Yao Y, Shi C and Wang C: Effective treatment of hypertension by recombinant Lactobacillus plantarum expressing angiotensin converting enzyme inhibitory peptide. Microb Cell Fact. 14(202)2015. | |
|
Cani PD and de Vos WM: Next-generation beneficial microbes: The case of Akkermansia muciniphila. Front Microbiol. 8(1765)2017.PubMed/NCBI View Article : Google Scholar | |
|
Rodríguez V, Asenjo JA and Andrews BA: Design and implementation of a high yield production system for recombinant expression of peptides. Microb Cell Fact. 13(65)2014.PubMed/NCBI View Article : Google Scholar | |
|
Sahdev S, Khattar SK and Saini KS: Production of active eukaryotic proteins through bacterial expression systems: A review of the existing biotechnology strategies. Mol Cell Biochem. 307:249–264. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Chance RE and Frank BH: Research, development, production, and safety of biosynthetic human insulin. Diabetes Care. 16 (Suppl 3):S133–S142. 1993.PubMed/NCBI View Article : Google Scholar | |
|
Whelan RA, Rausch S, Ebner F, Günzel D, Richter JF, Hering NA, Schulzke JD, Kühl AA, Keles A, Janczyk P, et al: A transgenic probiotic secreting a parasite immunomodulator for site-directed treatment of gut inflammation. Mol Ther. 22:1730–1740. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Zoetendal EG, Vaughan EE and De Vos WM: A microbial world within us. Mol Microbiol. 59:1639–1650. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Coeuret V, Dubernet S, Bernardeau M, Gueguen M and Vernoux JP: Isolation, characterisation and identification of lactobacilli focusing mainly on cheeses and other dairy products. Lait. 83:269–306. 2003. | |
|
Kikuchi Y, Kunitoh-Asari A, Hayakawa K, Imai S, Kasuya K, Abe K, Adachi Y, Fukudome S, Takahashi Y and Hachimura S: Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice. PLoS One. 9(e86416)2014.PubMed/NCBI View Article : Google Scholar | |
|
Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S and Black RE: Efficacy of probiotics in prevention of acute diarrhoea: A meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis. 6:374–382. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Wolvers D, Antoine JM, Myllyluoma E, Schrezenmeir J, Szajewska H and Rijkers GT: Guidance for substantiating the evidence for beneficial effects of probiotics: Prevention and management of infections by probiotics. J Nutr. 140:S698–S712. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Spath K, Heinl S and Grabherr R: ‘Direct cloning in Lactobacillus plantarum: Electroporation with non-methylated plasmid DNA enhances transformation efficiency and makes shuttle vectors obsolete’. Microb Cell Fact. 11(141)2012.PubMed/NCBI View Article : Google Scholar | |
|
Heiss S, Hörmann A, Tauer C, Sonnleitner M, Egger E, Grabherr R and Heinl S: Evaluation of novel inducible promoter/repressor systems for recombinant protein expression in Lactobacillus plantarum. Microb Cell Fact. 15(50)2016.PubMed/NCBI View Article : Google Scholar | |
|
Yadav R and Shukla P: An overview of advanced technologies for selection of probiotics and their expediency: A review. Crit Rev Food Sci Nutr. 57:3233–3242. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Allain T, Mansour NM, Bahr MMA, Martin R, Florent I, Langella P and Bermúdez-Humarán LG: A new lactobacilli in vivo expression system for the production and delivery of heterologous proteins at mucosal surfaces. FEMS Microbiol Lett. 363(fnw117)2016.PubMed/NCBI View Article : Google Scholar | |
|
Rong G, Corrie SR and Clark HA: In vivo biosensing: Progress and perspectives. ACS Sens. 2:327–338. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Rowland IR, Rumney CJ, Coutts JT and Lievense LC: Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. Carcinogenesis. 19:281–285. 1998.PubMed/NCBI View Article : Google Scholar | |
|
Rafter J, Bennett M, Caderni G, Clune Y, Hughes R, Karlsson PC, Klinder A, O'Riordan M, O'Sullivan GC, Pool-Zobel B, et al: Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients. Am J Clin Nutr. 85:488–496. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Le Leu RK, Hu Y, Brown IL, Woodman RJ and Young GP: Synbiotic intervention of Bifidobacterium lactis and resistant starch protects against colorectal cancer development in rats. Carcinogenesis. 31:246–251. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Bae EA, Han MJ, Song MJ and Kim DH: Purification of Rotavirus infection-inhibitory protein from Bifidobacterium breve K-110. J Microbiol Biotechnol. 12:553–556. 2002. | |
|
Patole SK, Rao SC, Keil AD, Nathan EA, Doherty DA and Simmer KN: Benefits of Bifidobacterium breve M-16V Supplementation in preterm neonates-A retrospective cohort study. PLoS One. 11(e0150775)2016.PubMed/NCBI View Article : Google Scholar | |
|
Venturi A, Gionchetti P, Rizzello F, Johansson R, Zucconi E, Brigidi P, Matteuzzi D and Campieri M: Impact on the composition of the faecal flora by a new probiotic preparation: Preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther. 13:1103–1108. 1999.PubMed/NCBI View Article : Google Scholar | |
|
Yadav R, Kumar V, Baweja M and Shukla P: Gene editing and genetic engineering approaches for advanced probiotics: A review. Crit Rev Food Sci Nutr. 58:1735–1746. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Wei C, Xun AY, Wei XX, Yao J, Wang JY, Shi RY, Yang GH, Li YX, Xu ZL, Lai MG, et al: Bifidobacteria expressing tumstatin protein for antitumor therapy in tumor-bearing mice. Technol Cancer Res Treat. 15:498–508. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Xu YF, Zhu LP, Hu B, Fu GF, Zhang HY, Wang JJ and Xu GX: A new expression plasmid in Bifidobacterium longum as a delivery system of endostatin for cancer gene therapy. Cancer Gene Ther. 14:151–157. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Zhu LP, Yin Y, Xing J, Li C, Kou L, Hu B, Wu ZW, Wang JJ and Xu GX: Therapeutic efficacy of Bifidobacterium longum-mediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors. Cancer Sci. 100:1986–1990. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Hu B, Kou L, Li C, Zhu LP, Fan YR, Wu ZW, Wang JJ and Xu GX: Bifidobacterium longum as a delivery system of TRAIL and endostatin cooperates with chemotherapeutic drugs to inhibit hypoxic tumor growth. Cancer Gene Ther. 16:655–663. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Bolhassani A and Zahedifard F: Therapeutic live vaccines as a potential anticancer strategy. Int J Cancer. 131:1733–1743. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Chen T, Zhao X, Ren Y, Wang Y, Tang X, Tian P, Wang H and Xin H: Triptolide modulates tumour-colonisation and anti-tumour effect of attenuated Salmonella encoding DNase I. Appl Microbiol Biotechnol. 103:929–939. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Shahabi V, Reyes-Reyes M, Wallecha A, Rivera S, Paterson Y and MacIag P: Development of a Listeria monocytogenes based vaccine against prostate cancer. Cancer Immunol Immunother. 57:1301–1313. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Chen Y, Yang D, Li S, Gao Y, Jiang R, Deng L, Frankel FR and Sun B: Development of a Listeria monocytogenes-based vaccine against hepatocellular carcinoma. Oncogene. 31:2140–2152. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Chan CT, Lee JW, Cameron DE, Bashor CJ and Collins JJ: ‘Deadman’ and ‘Passcode’ microbial kill switches for bacterial containment. Nat Chem Biol. 12:82–86. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Derrien M, Vaughan EE, Plugge CM and de Vos WM: Akkermansia municiphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 54:1469–1476. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Reunanen J, Kainulainen V, Huuskonen L, Ottman N, Belzer C, Huhtinen H, de Vos WM and Satokari R: Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Appl Environ Microbiol. 81:3655–3662. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Ottman N, Geerlings SY, Aalvink S, de Vos WM and Belzer C: Action and function of Akkermansia muciniphila in microbiome ecology, health and disease. Best Pract Res Clin Gastroenterol. 31:637–642. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Thibault R, Blachier F, Darcy-Vrillon B, De Coppet P, Bourreille A and Segain JP: Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: A transport deficiency. Inflamm Bowel Dis. 16:684–695. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Puertollano E, Kolida S and Yaqoob P: Biological significance of short-chain fatty acid metabolism by the intestinal microbiome. Curr Opin Clin Nutr Metab Care. 17:139–144. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Ottman N, Reunanen J, Meijerink M, Pietilä TE, Kainulainen V, Klievink J, Huuskonen L, Aalvink S, Skurnik M, Boeren S, et al: Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS One. 12(e0173004)2017.PubMed/NCBI View Article : Google Scholar | |
|
Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, et al: A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 23:107–113. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, et al: Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 384:766–781. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR and Delzenne NM: Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 50:2374–2383. 2007.PubMed/NCBI View Article : Google Scholar | |
|
GBD 2015 Obesity Collaborators. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH, Moradi-Lakeh M, et al: Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 377:13–27. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Santacruz A, Collado MC, García-Valdés L, Segura MT, Martín-Lagos JA, Anjos T, Martí-Romero M, Lopez RM, Florido J, Campoy C and Sanz Y: Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr. 104:83–92. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Karlsson CL, Önnerfält J, Xu J, Molin G, Ahrné S and Thorngren-Jerneck K: The microbiota of the gut in preschool children with normal and excessive body weight. Obesity (Silver Spring). 20:2257–2261. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, et al: Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA. 110:9066–9071. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, et al: Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: A proof-of-concept exploratory study. Nat Med. 25:1096–1103. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Hu FB, Manson JAE and Willett WC: Types of dietary fat and risk of coronary heart disease: A critical review. J Am Coll Nutr. 20:5–19. 2001.PubMed/NCBI View Article : Google Scholar | |
|
Almdal T, Scharling H, Jensen JS and Vestergaard H: The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: A population-based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med. 164:1422–1426. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Maleckas A, Venclauskas L, Wallenius V and Fändriks HL: Metabolic surgery in the treatment of type 2 diabetes mellitus. Oxford Textb Endocrinol Diabetes. 61:257–264. 2011. | |
|
Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, et al: Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 56:1761–1772. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, Chen Y and Ji L: Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One. 8(e711108)2013.PubMed/NCBI View Article : Google Scholar | |
|
Hansen CH, Krych L, Nielsen DS, Vogensen FK, Hansen LH, Sørensen SJ, Buschard K and Hansen AK: Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia. 55:2285–2294. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Pedersen HK, et al: Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 528:262–266. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Tedgui A and Mallat Z: Cytokines in atherosclerosis: Pathogenic and regulatory pathways. Physiol Rev. 86:515–581. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, et al: Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 5(14)2017.PubMed/NCBI View Article : Google Scholar | |
|
Jonsson AL and Bäckhed F: Role of gut microbiota in atherosclerosis. Nat Rev Cardiol. 14:79–87. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Barrington WT and Lusis AJ: Atherosclerosis: Association between the gut microbiome and atherosclerosis. Nat Rev Cardiol. 14:699–700. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Li J, Lin S, Vanhoutte PM, Woo CW and Xu A: Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe-/- Mice. Circulation. 133:2434–2446. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Campion D, Ponzo P, Alessandria C, Saracco GM and Balzola F: The role of microbiota in autism spectrum disorders. Minerva Gastroenterol Dietol. 64:333–350. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT and Conlon MA: Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Appl Environ Microbiol. 77:6718–6721. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Naito Y, Uchiyama K and Takagi T: A next-generation beneficial microbe: Akkermansia muciniphila. J Clin Biochem Nutr. 63:33–35. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al: Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 359:91–97. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Zheng H, Liang H, Wang Y, Miao M, Shi T, Yang F, Liu E, Yuan W, Ji ZS and Li DK: Altered gut microbiota composition associated with eczema in infants. PLoS One. 11(e0166026)2016.PubMed/NCBI View Article : Google Scholar | |
|
Wu W, Lv L, Shi D, Ye J, Fang D, Guo F, Li Y, He X and Li L: Protective effect of Akkermansia muciniphila against immune-mediated liver injury in a mouse model. Front Microbiol. 8(1804)2017.PubMed/NCBI View Article : Google Scholar | |
|
Png CW, Lindén SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, McGuckin MA and Florin TH: Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 105:2420–2428. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Wang HX, Liu M, Weng SY, Li JJ, Xie C, He HL, Guan W, Yuan YS and Gao J: Immune mechanisms of Concanavalin a model of autoimmune hepatitis. World J Gastroenterol. 18:119–125. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Drell T, Larionova A, Voor T, Simm J, Julge K, Heilman K, Tillmann V, Štšepetova J and Sepp E: Differences in gut microbiota between atopic and healthy children. Curr Microbiol. 71:177–183. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Lukovac S, Belzer C, Pellis L, Keijser BJ, de Vos WM, Montijn RC and Roeselers G: Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. mBio. 5:e01438–14. 2014.PubMed/NCBI View Article : Google Scholar | |
|
van Passel MWJ, Kant R, Zoetendal EG, Plugge CM, Derrien M, Malfatti SA, Chain PS, Woyke T, Palva A, de Vos WM and Smidt H: The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS One. 6(e16876)2011.PubMed/NCBI View Article : Google Scholar | |
|
Caputo A, Dubourg G, Croce O, Gupta S, Robert C, Papazian L, Rolain JM and Raoult D: Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool. Biol Direct. 10(5)2015.PubMed/NCBI View Article : Google Scholar | |
|
Guo X, Li S, Zhang J, Wu F, Li X, Wu D, Zhang M, Ou Z, Jie Z, Yan Q, et al: Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas. BMC Genomics. 18(800)2017.PubMed/NCBI View Article : Google Scholar | |
|
Ouwerkerk JP, Aalvink S, Belzer C and De Vos WM: Preparation and preservation of viable Akkermansia muciniphila cells for therapeutic interventions. Benef Microbes. 8:163–169. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Ouwerkerk JP, van der Ark KCH, Davids M, Claassens NJ, Finestra TR, de Vos WM and Belzer C: Adaptation of Akkermansia muciniphila to the oxic-anoxic interface of the mucus layer. Appl Environ Microbiol. 82:6983–6993. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Vectors DP: Suicide gene therapy of cancer. Mol Ther. 3:S98–S115. 2001. | |
|
Baban CK, Cronin M, O'Hanlon D, O'Sullivan GC and Tangney M: Bacteria as vectors for gene therapy of cancer. Bioeng Bugs. 1:385–394. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Pedrolli DB, Ribeiro NV, Squizato PN, de Jesus VN and Cozetto DA: Team AQA Unesp at iGEM 2017. Engineering microbial living therapeutics: The synthetic biology toolbox. Trends Biotechnol. 37:100–115. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Waller MC, Bober JR, Nair NU and Beisel CL: Toward a genetic tool development pipeline for host-associated bacteria. Curr Opin Microbiol. 38:156–164. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Riglar DT and Silver PA: Engineering bacteria for diagnostic and therapeutic applications. Nat Rev Microbiol. 16:214–225. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Welker DL, Hughes JE, Steele JL and Broadbent R: High efficiency electrotransformation of Lactobacillus casei. FEMS Microbiol Lett. 362:1–6. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Walsh M, Tangney M, O'Neill MJ, Larkin JO, Soden DM, McKenna SL, Darcy R, O'Sullivan GC and O'Driscoll CM: Evaluation of cellular uptake and gene transfer efficiency of pegylated poly-L-lysine compacted DNA: Implications for cancer gene therapy. Mol Pharm. 3:644–653. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Ahmad S, Casey G, Sweeney P, Tangney M and O'Sullivan GC: Optimised electroporation mediated DNA vaccination for treatment of prostate cancer. Genet Vaccines Ther. 8(1)2010.PubMed/NCBI View Article : Google Scholar | |
|
Kado CI: Historical events that spawned the field of plasmid biology. Microbiol Spectr 2, 2014. | |
|
St-Pierre F, Cui L, Priest DG, Endy D, Dodd IB and Shearwin KE: One-step cloning and chromosomal integration of DNA. ACS Synth Biol. 2:537–541. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Urnov FD, Rebar EJ, Holmes MC, Zhang HS and Gregory PD: Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 11:636–646. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF, Meng X, Paschon DE, Leung E, Hinkley SJ, et al: A TALE nuclease architecture for efficient genome editing. Nat Biotechnol. 29:143–148. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR and Church GM: Programming cells by multiplex genome engineering and accelerated evolution. Nature. 460:894–898. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Kuipers OP, Beerthuyzen MM, de Ruyter PG, Luesink EJ and de Vos WM: Autoregulation of nisin biosynthesis in lactococcus lactis by signal transduction. J Biol Chem. 270:27299–27304. 1995.PubMed/NCBI View Article : Google Scholar | |
|
Van der Meer JR, Polman J, Beerthuyzen MM, Siezen RJ, Kuipers OP and De Vos WM: Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis. J Bacteriol. 175:2578–2588. 1993.PubMed/NCBI View Article : Google Scholar | |
|
Engelke G, Gutowski-Eckel Z, Kiesau P, Siegers K, Hammelmann M and Entian KD: Regulation of nisin biosynthesis and immunity in Lactococcus lactis 6F3. Appl Environ Microbiol. 60:814–825. 1994.PubMed/NCBI View Article : Google Scholar | |
|
Kleerebezem M, Bongers R, Rutten G, Vos WMD and Kuipers OP: Autoregulation of subtilin biosynthesis in Bacillus subtilis: The role of the spa-box in subtilin-responsive promoters. Peptides. 25:1415–1424. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Mohseni AH, Razavilar V, Keyvani H, Razavi MR and Khavari-Nejad RA: Efficient production and optimization of E7 oncoprotein from Iranian human papillomavirus type 16 in Lactococcus lactis using nisin-controlled gene expression (NICE) system. Microb Pathog. 110:554–560. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Van Hoang V, Ochi T, Kurata K, Arita Y, Ogasahara Y and Enomoto K: Nisin-induced expression of recombinant T cell epitopes of major Japanese cedar pollen allergens in Lactococcus lactis. Appl Microbiol Biotechnol. 102:261–268. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Kaiser AD: A genetic study of the temperate coliphage λ. Virology. 1:424–443. 1955.PubMed/NCBI View Article : Google Scholar | |
|
Carter DM and Radding CM: The role of exonuclease and beta protein of phage lambda in genetic recombination. II. Substrate specificity and the mode of action of lambda exonuclease. J Biol Chem. 246:2502–2512. 1971.PubMed/NCBI | |
|
Murphy KC: Lambda Gam protein inhibits the helicase and chi-stimulated recombination activities of Escherichia coli RecBCD enzyme. J Bacteriol. 173:5808–5821. 1991.PubMed/NCBI View Article : Google Scholar | |
|
Karu AE, Sakaki Y, Echols H and Linn S: The gamma protein specified by bacteriophage gamma. Structure and inhibitory activity for the recBC enzyme of Escherichia coli. J Biol Chem. 250:7377–7387. 1975.PubMed/NCBI | |
|
Murphy KC: λ recombination and recombineering. EcoSal Plus 7, 2016. | |
|
Juhas M and Ajioka JW: Lambda Red recombinase-mediated integration of the high molecular weight DNA into the Escherichia coli chromosome. Microb Cell Fact. 15(172)2016.PubMed/NCBI View Article : Google Scholar | |
|
Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J and Charpentier E: CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature. 471:602–607. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Bolotin A, Quinquis B, Sorokin A and Dusko Ehrlich S: Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology (Reading). 151:2551–2561. 2005.PubMed/NCBI View Article : Google Scholar | |
|
Deveau H, Barrangou R, Garneau JE, Labonté J, Fremaux C, Boyaval P, Romero DA, Horvath P and Moineau S: Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. J Bacteriol. 190:1390–1400. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Tong Y, Charusanti P, Zhang L, Weber T and Lee SY: CRISPR-Cas9 based engineering of actinomycetal genomes. ACS Synth Biol. 4:1020–1029. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Garneau JE, Dupuis MÈ, Villion M, Romero DA, Barrangou R, Boyaval P, Fremaux C, Horvath P, Magadán AH and Moineau S: The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. 468:67–71. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Jiang W, Bikard D, Cox D, Zhang F and Marraffini LA: RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol. 31:233–239. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Oh JH and Van Pijkeren JP: CRISPR-Cas9-assisted recombineering in Lactobacillus reuteri. Nucleic Acids Res. 42(e131)2014.PubMed/NCBI View Article : Google Scholar | |
|
van der Els S, James JK, Kleerebezem M and Bron PA: Versatile Cas9-driven subpopulation selection toolbox for Lactococcus lactis. Appl Environ Microbiol. 84:e02752–17. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Manghwar H, Lindsey K, Zhang X and Jin S: CRISPR/Cas system: Recent advances and future prospects for genome editing. Trends Plant Sci. 24:1102–1125. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Gauttam R, Seibold GM, Mueller P, Weil T, Weiß T, Handrick R and Eikmanns BJ: A simple dual-inducible CRISPR interference system for multiple gene targeting in Corynebacterium glutamicum. Plasmid. 103:25–35. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Crawley AB, Henriksen JR and Barrangou R: CRISPRdisco: An automated pipeline for the discovery and analysis of CRISPR-Cas systems. CRISPR J. 1:171–181. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Takei S, Omoto C, Kitagawa K, Morishita N, Katayama T, Shigemura K, Fujisawa M, Kawabata M, Hotta H and Shirakawa T: Oral administration of genetically modified Bifidobacterium displaying HCV-NS3 multi-epitope fusion protein could induce an HCV-NS3-specific systemic immune response in mice. Vaccine. 32:3066–3074. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Pathmakanthan S, Meance S and Edwards CA: Probiotics: A review of human studies to date and methodological approaches. Microb Ecol Health Dis. 12:10–30. 2000. | |
|
Lawenius L, Scheffler JM, Gustafsson KL, Henning P, Nilsson KH, Colldén H, Islander U, Plovier H, Cani PD, de Vos WM, et al: Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss. Am J Physiol Endocrinol Metab. 318:E480–E491. 2020.PubMed/NCBI View Article : Google Scholar |
