scholarly journals Native and Engineered Probiotics: Promising Agents against Related Systemic and Intestinal Diseases

2022 ◽  
Vol 23 (2) ◽  
pp. 594
Author(s):  
Haokun Shen ◽  
Zitong Zhao ◽  
Zengjue Zhao ◽  
Yuyi Chen ◽  
Linghua Zhang

Intestinal homeostasis is a dynamic balance involving the interaction between the host intestinal mucosa, immune barrier, intestinal microecology, nutrients, and metabolites. Once homeostasis is out of balance, it will increase the risk of intestinal diseases and is also closely associated with some systemic diseases. Probiotics (Escherichia coli Nissle 1917, Akkermansia muciniphila, Clostridium butyricum, lactic acid bacteria and Bifidobacterium spp.), maintaining the gut homeostasis through direct interaction with the intestine, can also exist as a specific agent to prevent, alleviate, or cure intestinal-related diseases. With genetic engineering technology advancing, probiotics can also show targeted therapeutic properties. The aims of this review are to summarize the roles of potential native and engineered probiotics in oncology, inflammatory bowel disease, and obesity, discussing the therapeutic applications of these probiotics.

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 738
Author(s):  
Jiayu Ye ◽  
Lauren A. E. Erland ◽  
Sandeep K. Gill ◽  
Stephanie L. Bishop ◽  
Andrea Verdugo-Meza ◽  
...  

The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs’ persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic mice treated with either BioPersist or BioColoniz as compared to their unmodified parent strains (Escherichia coli Nissle 1917 [EcN] and Lactobacillus reuteri, respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.


2015 ◽  
Vol 41 (08) ◽  
Author(s):  
K Rilling ◽  
T Abou-Ghazalé ◽  
R Scherer ◽  
H Harder-de'Heureuse ◽  
B Wiedenmann ◽  
...  

2015 ◽  
Vol 41 (08) ◽  
Author(s):  
M Schultz ◽  
S Watzl ◽  
H-J Linde ◽  
UG Strauch ◽  
F Obermeier ◽  
...  

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A611-A611
Author(s):  
Fernando Canale ◽  
Camilla Basso ◽  
Ning Li ◽  
Anna Sokolovska ◽  
Michela Perotti ◽  
...  

BackgroundThe availability of L-arginine in tumors is a key determinant of an efficient anti-tumor T cell response. Consequently, the elevation of typically low L-arginine levels within the tumor may greatly potentiate the anti-tumor responses of immune check point inhibitors, such as PD-L1 blocking antibodies. However, currently no means are available to locally increase intra-tumoral L-arginine levels.MethodsWe used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumors and continuously converts ammonia, a metabolic waste product that accumulates in tumors, into L-arginine.ResultsColonization of tumors with these bacteria elevated intra-tumoral L-arginine concentrations, increased the amount of tumor-infiltrating T cells, and had striking synergistic effects with PD-L1 blocking antibodies in the clearance of tumors. The anti-tumor effect of the living therapeutic was mediated by L-arginine and was dependent on T cells.ConclusionsThese results show that engineered microbial therapies enable metabolic modulation of the tumor microenvironment leading to enhanced efficacy of immunotherapies.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4733
Author(s):  
Kiran Reddi ◽  
Hanxuan Li ◽  
Wei Li ◽  
Sarada Tetali

Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 583
Author(s):  
Ze-Jun Yang ◽  
Bo-Ya Wang ◽  
Tian-Tian Wang ◽  
Fei-Fei Wang ◽  
Yue-Xin Guo ◽  
...  

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.


Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 241-250 ◽  
Author(s):  
Anne-Kathrin Claes ◽  
Jun Yu Zhou ◽  
Dana J. Philpott

The NOD-like receptors (NLRs) are cytosolic pattern-recognition receptors, which are critically involved in mucosal immune defense. The association of the NLR, NOD2, with inflammatory bowel disease first pointed to the NLRs potential function as guardians of the intestinal barrier. Since then, several studies have emphasized the importance of NLRs in maintaining gut homeostasis and intestinal infections, and in shaping the microbiota. In this review, we will highlight the function of NLRs in intestinal inflammation.


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