Positive Interventional Effect of Engineered Butyrate-Producing Bacteria on Metabolic Disorders and Intestinal Flora Disruption in Obese Mice

Wang, Lina; Cheng, Xiaoming; Bai, Liang; Gao, Mengxue; Kang, Guangbo; Cao, Xiaocang; Huang, He

doi:10.1128/spectrum.01147-21

Cited by 28 publications

(29 citation statements)

References 64 publications

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“…Interestingly, Lactobacillus is the most abundant genus in the community, and Bifidobacterium is within the top 10 (Figure 4C). These confirm our previous in vivo study, implanted EBPB in mice enriched Lactobacillus and Bifidobacterium (Bai et al, 2020;Wang et al, 2022).…”

Section: Isolating Gut Bacteria Metabolically Associated With Ebpbsupporting

confidence: 92%

“…Engineered butyrate-producing BsS-RS06551 strain based on Bacillus subtilis SCK6 host (EBPB) were created in-house previously ( Wang et al., 2022 ). The butyrate yield reached 1.5 g/l, and the supernatant was weakly acidic.…”

Section: Methodsmentioning

confidence: 99%

“…metagenomic study revealed an altered gut microbiota (Wang et al, 2022). To illustrate the mechanism, it is necessary to understand who interacts with EBPB in the gut microbiota.…”

Section: Isolating Gut Bacteria Metabolically Associated With Ebpbmentioning

confidence: 99%

“…On the other hand, bacteria have been used as therapies for centuries, and recent advances in synthetic biology have unlocked tremendous opportunities for engineered bacteria in diagnosis and therapies (Riglar and Silver, 2018). Previously, we have engineered butyrate-producing bacteria (EBPB) and confirmed its potential anti-obesity effects on mice (Wang et al, 2022). Through metagenomic analysis of the gut microbiota, we found that after the long-term use of the EBPB bacteria, the abundance of beneficial bacteria, such as Bifidobacterium, Lactobacillus, and Akkermansia, increased.…”

Section: Introductionmentioning

confidence: 99%

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A droplet-based microfluidic approach to isolating functional bacteria from gut microbiota

Yin

Chen

Li³

et al. 2022

Front. Cell. Infect. Microbiol.

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Metabolic interactions within gut microbiota play a vital role in human health and disease. Targeting metabolically interacting bacteria could provide effective treatments; however, obtaining functional bacteria remains a significant challenge due to the complexity of gut microbiota. Here, we developed a facile droplet-based approach to isolate and enrich functional gut bacteria that could utilize metabolites from an engineered butyrate-producing bacteria (EBPB) of anti-obesity potential. This involves the high throughput formation of single-bacteria droplets, followed by culturing “droplets” on agar plates to form discrete single-cell colonies. This approach eliminates the need for sophisticated s instruments to sort droplets and thus allows the operation hosted in a traditional anaerobic chamber. In comparison to the traditional culture, the droplet-based approach obtained a community of substantially higher diversity and evenness. Using the conditioned plates containing metabolites from the EBPB supernatant, we obtained gut bacteria closely associated or interacting with the EBPB. These include anaerobic Lactobacillus and Bifidobacterium, which are often used as probiotics. The study illustrates the potential of our approach in the search for the associated bacteria within the gut microbiota and retrieving those yet-to-be cultured.

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Section: Isolating Gut Bacteria Metabolically Associated With Ebpbsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

“…metagenomic study revealed an altered gut microbiota (Wang et al, 2022). To illustrate the mechanism, it is necessary to understand who interacts with EBPB in the gut microbiota.…”

Section: Isolating Gut Bacteria Metabolically Associated With Ebpbmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A droplet-based microfluidic approach to isolating functional bacteria from gut microbiota

Yin

Chen

Li³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The engineered strain could degrade phenylalanine in the gastrointestinal tract (Puurunen et al, 2021). A butyrate-producing bacteria, recombinant B. subtilis BsS-RS06550 with high butyric acid production was constructed using synthetic biological strategies could effectively regulate body metabolism and intestinal flora disruption (Bai et al, 2020;Wang et al, 2022).The modified strains can increase the variety and number of available strains to the bacterial combination. So far, the engineered strain alone against certain diseases, such as phenylketonuria (Puurunen et al, 2021), liver cirrhosis (https://clinicaltrials.gov/ct2/show/NCT03447730?…”

Section: Perspectives Of Engineered Consortium Transplantationmentioning

confidence: 99%

Evolutionary Insights Into Microbiota Transplantation in Inflammatory Bowel Disease

Wang

Zhao²,

Feng³

et al. 2022

Front. Cell. Infect. Microbiol.

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The intestinal microbiome plays an essential role in human health and disease status. So far, microbiota transplantation is considered a potential therapeutic approach for treating some chronic diseases, including inflammatory bowel disease (IBD). The diversity of gut microbiota is critical for maintaining resilience, and therefore, transplantation with numerous genetically diverse gut microbiota with metabolic flexibility and functional redundancy can effectively improve gut health than a single probiotic strain supplement. Studies have shown that natural fecal microbiota transplantation or washing microbiota transplantation can alleviate colitis and improve intestinal dysbiosis in IBD patients. However, unexpected adverse reactions caused by the complex and unclear composition of the flora limit its wider application. The evolving strain isolation technology and modifiable pre-existing strains are driving the development of microbiota transplantation. This review summarized the updating clinical and preclinical data of IBD treatments from fecal microbiota transplantation to washing microbiota transplantation, and then to artificial consortium transplantation. In addition, the factors considered for strain combination were reviewed. Furthermore, four types of artificial consortium transplant products were collected to analyze their combination and possible compatibility principles. The perspective on individualized microbiota transplantation was also discussed ultimately.

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Sequential delivery of photosensitizers and checkpoint inhibitors by engineered bacteria for enhanced cancer photodynamic immunotherapy

Liu,

Fan,

Zhang

et al. 2024

Biotech & Bioengineering

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Engineered bacteria‐based cancer therapy has increasingly been considered to be a promising therapeutic strategy due to the development of synthetic biology. Wherein, engineering bacteria‐mediated photodynamic therapy (PDT)‐immunotherapy shows greater advantages and potential in treatment efficiency than monotherapy. However, the unsustainable regeneration of photosensitizers (PSs) and weak immune responses limit the therapeutic efficiency. Herein, we developed an engineered bacteria‐based delivery system for sequential delivery of PSs and checkpoint inhibitors in cancer PDT‐immunotherapy. The biosynthetic pathway of 5‐aminolevulinic acid (5‐ALA) was introduced into Escherichia coli, yielding a supernatant concentration of 172.19 mg/L after 10 h of growth. And another strain was endowed with the light‐controllable releasement of anti‐programmed cell death‐ligand 1 nanobodies (anti‐PD‐L1). This system exhibited a collaborative effect, where PDT initiated tumor cell death and the released tumor cell fragments stimulated immunity, followed by the elimination of residual tumor cells. The tumor inhibition rate reached 74.97%, and the portion of activated T cells and inflammatory cytokines were reinforced. The results demonstrated that the engineered bacteria‐based collaborative system could sequentially deliver therapeutic substance and checkpoint inhibitors, and achieve good therapeutic therapy. This paper will provide a new perspective for the cancer PDT‐immunotherapy.

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Positive Interventional Effect of Engineered Butyrate-Producing Bacteria on Metabolic Disorders and Intestinal Flora Disruption in Obese Mice

Abstract: Obesity is a chronic metabolic disease with an imbalance between energy intake and energy expenditure, and obesity-related metabolic diseases have become increasingly common. There is an urgent need to develop effective interventions for the prevention and treatment of obesity.

Cited by 28 publications

References 64 publications

A droplet-based microfluidic approach to isolating functional bacteria from gut microbiota

A droplet-based microfluidic approach to isolating functional bacteria from gut microbiota

Evolutionary Insights Into Microbiota Transplantation in Inflammatory Bowel Disease

Sequential delivery of photosensitizers and checkpoint inhibitors by engineered bacteria for enhanced cancer photodynamic immunotherapy

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