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      Harnessing the potential of Lactobacillus species for therapeutic delivery at the lumenal-mucosal interface

      1 , 2 , 3 , * , 3
      Future Science OA
      Future Science Ltd
      cytokine stimulation, delivery vehicle, immunomodulation, Lactobacillus, microbiome, probiotic, therapy, vaccine

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          Lactobacillus species have been studied for over 30 years in their role as commensal organisms in the human gut. Recently there has been a surge of interest in their abilities to natively and recombinantly stimulate immune activities, and studies have identified strains and novel molecules that convey particular advantages for applications as both immune adjuvants and immunomodulators. In this review, we discuss the recent advances in Lactobacillus-related activity at the gut/microbiota interface, the efforts to probe the boundaries of the direct and indirect therapeutic potential of these bacteria, and highlight the continued interest in harnessing the native capacity for the production of biogenic compounds shown to influence nervous system activity. Taken together, these aspects underscore Lactobacillus species as versatile therapeutic delivery vehicles capable of effector production at the lumenal-mucosal interface, and further establish a foundation of efficacy upon which future engineered strains can expand.

          Lay abstract

          Bacteria such as Lactobacillus species have traditionally maintained positive association with gastrointestinal health. This review summarizes recent research relating to human health associated Lactobacillus administration on cellular and systematic levels. As techniques in molecular and synthetic biology continue to advance, the potential to increase the therapeutic scope and efficacy of Lactobacillus cultures increases regarding target molecule production, immune system influence, vaccination and nervous system activities.

          Most cited references202

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          Regional specialization within the intestinal immune system.

          The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease in the intestine.
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            Neurotransmitter modulation by the gut microbiota

            The gut microbiota – the trillions of bacteria that reside within the gastrointestinal tract – has been found to not only be an essential component immune and metabolic health, but also seems to influence development and diseases of the enteric and central nervous system, including motility disorders, behavioral disorders, neurodegenerative disease, cerebrovascular accidents, and neuroimmune-mediated disorders. By leveraging animal models, several different pathways of communication have been identified along the “gut-brain-axis” including those driven by the immune system, the vagus nerve, or by modulation of neuroactive compounds by the microbiota. Of the latter, bacteria have been shown to produce and/or consume a wide range of mammalian neurotransmitters, including dopamine, norepinephrine, serotonin, or gamma-aminobutyric acid (GABA). Accumulating evidence in animals suggests that manipulation of these neurotransmitters by bacteria may have an impact in host physiology, and preliminary human studies are showing that microbiota-based interventions can also alter neurotransmitter levels. Nonetheless, substantially more work is required to determine whether microbiota-mediated manipulation of human neurotransmission has any physiological implications, and if so, how it may be leveraged therapeutically. In this review this exciting route of communication along the gut-brain-axis, and accompanying data, are discussed.
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              Biofilm exopolysaccharides: a strong and sticky framework


                Author and article information

                Future Sci OA
                Future Sci OA
                Future Science OA
                Future Science Ltd (London, UK )
                04 February 2021
                April 2021
                04 February 2021
                : 7
                : 4
                : FSO671
                [1 ]National Research Council Postdoctoral Fellow sited in US Naval Research Laboratory, Code 6900, Center for Bio/Molecular Science & Engineering, 4555 Overlook Ave SW, Washington DC, 20375, USA.
                [2 ]American Society for Engineering Education Postdoctoral Fellow sited in US Naval Research Laboratory, Code 6900, Center for Bio/Molecular Science & Engineering, 4555 Overlook Ave SW, Washington DC, 20375, USA.
                [3 ]US Naval Research Laboratory, Code 6900, Center for Bio/Molecular Science & Engineering, 4555 Overlook Ave SW, Washington DC, 20375, USA
                Author notes
                [* ]Author for correspondence: scott.walper@ 123456nrl.navy.mil
                Author information
                © 2021 Department of the Navy

                This work is licensed under the Creative Commons Attribution 4.0 License

                : 28 August 2020
                : 18 November 2020
                : 04 February 2021
                Page count
                Pages: 23
                Funded by: US Naval Research Laboratory;

                cytokine stimulation,delivery vehicle,immunomodulation,lactobacillus,microbiome,probiotic,therapy,vaccine


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