Meal Manipulation of Microbiome

Meal Manipulation of Microbiome

Background Information

The microbiome communities comprising of bacteria, fungi among other microorganisms, have been referred by many scientists as the microbiota, and sometimes microflora, with the genes encoding them termed as the microbiomes. The health organism has unique features that readily distinguish them from the non-healthy individual body, rendering those able to distinguish between healthy and unhealthy microorganisms able to detect and identify a disease that has an association with a microbiome. People have acknowledged the high number of benefits accrued from the microbiomes that can withstand the entire changes that occur during stress psychologically. However, following the less diverse microbiota associated with infection, the benefit of the microbiomes decreases, leading to lower diseases once there is inflammation. Besides, the researchers are facing a challenge in understanding the diversified characteristics of the microbiomes among individuals. Such traditional methods as cultivation of the organisms have resulted in unreliable information as far as the manipulation of microbiomes in the medical perspective is concerned. Some approaches like NGS have helped to understand the uniqueness of the microbiota population as well as their combinations, identifying the archaea, bacteria, and viruses in the body. Disturbances in the ecology of the microbial are associated with several diseases ranging from diabetes to inflammatory bowel disease, among others. The human microbiome is applicable as the critical diagnostic biomarker; hence the today’s researchers focus on the therapeutic role of the microbiome. Different human bodies have different and unique microbiota, and the inflammatory effects, as well as effects of cancer on each organ, are differently received, and understanding of the interpersonal microbiomes changes is a challenge. The various outcomes of the microbiome and differences in the patient therapies to cancer and drug response are the main objective behind the manipulation of microbiomes to apply in medical contexts..

Introduction

Currently, the medical importance of the microbiome in human health and diseases has been made clear. Ideally, the intimate host-microbiota association affects the metabolism, immunity, and the gut-brain axis, where the interactions between the host and the microbiome occur in various sites of the body, including the nasopharynx, oral cavity, respiratory tract, gastrointestinal tract, reproductive tract of females, and skin. The new understanding regarding the host-microbiome interactions and effects motivates the development of microbiome-based therapeutics for the treatment of diseases which have links to the diverse microbial communities. For instance, the genetic engineering of microbes, inclusive of the natural members of the microbiota, enables the designing of microorganisms that can sense and treat bacterial disease. However, researchers have developed interests in studying the microbial consortia, the host-microbe interactions, the roles of viruses, as well as modulation of the microbiome processes for applications in the medical field as therapies, beyond individual bacteria. Despite significant studies in the stated targets, the learners face a challenge in translating most processes of the microbiomes into clinical applications.

Manipulation of the microbiomes encompasses the alteration of the microbiota population as well as kits composition to modify the functional metabolism of the microbiome in such a way that it may promote health, restoring the microbiome balance. However, the manipulation is facilitated by microbiome engineering.

Microbial communities, as well as their collective genomes, can form the gut microbiome, with the bacteria as the primary contributor. The secreted metabolites necessitate the bacteria to interact with the host, which in turn, influences human health and their physiology. Perturbations about the microbiota and metabolome have an association with several diseases and metabolic conditions like diabetes. Since the knowledge concerning the relevant host-microbiome interactions, including the tools of genetic engineering are increasing among the researchers, favoring the targeted manipulations is also gaining popularity for the therapeutic applications of the manipulated microbiomes. Manipulating the gut microbiome is necessary through the alteration of the microbiota population and composition as well or through the modification of the functional metabolic activities of the microbiomes that impact the restoration of microbiome balances and promotion of health.

As far as the manipulation of the microbiomes to initiate a medically significant effect, Lactobacillus species, Escherichia coli, and Bifidobacterium species offer numerous health benefits, as they are potentially able to treat several diseases. The organisms can be found in over-the-counter probiotics. The expression of recombinant of the therapeutic biomolecules from the engineering of the microbes increases the benefits and helps in preventing infections, resolving inflammation, and treating metabolic disorders. Development of bacteria may deliver drugs at the site of infection, which enhances the bioavailability and reduces the activation of drugs. Furthermore, outfitting the bacteria with sensors that detect biomarkers of diseases, triggering on-demand drug release is possible. Fully autonomous of cell-based therapeutics to restore the health of the infected human has not yet encountered advancements in the clinic, while the requisite technology is readily available. However, the individual microbiomes can be applied in the treatment of disease as consortia or individually. Contrary, the identification of the bacteria and customizations of the communities of bacteria for addressing complex human conditions despite the diversities in the microbiota associated with social host pose a challenge while creating microbiota-based therapies for infections.

First, the application of engineered bacteria is seen in the treatment of bacterial and viral diseases. Considerably, the normal flora present in healthy persons resists the colonization of host by pathogens; hence cellular engineering possibly augments such resistance. For instance, Escherichia coli Nissle 1917 is a probiotic strain, designed for inhibiting the virulence of Vibrio cholera among the infants. V. cholerae is dependent on quorum sensing while coordinating the expression of particular virulence factors considering the cell density. Administration of E. coli engineered to help in interfering with the quorum sensing system results in the increment of survival chances of infected humans, and a decrement in bacterial burden and expression of cholera toxin. Similarly, Lactobacillus jensenii, with genetic modifications, was observed to prevent transmission of chimeric simian or; instead, the human immunodeficiency virus (SHIV), tested using the rhesus macaque monkey. Bacteria modifications were meant to express the cyanovirin-N, which is an antiviral molecule, and to decrease the occurrence of SHIV as well as an optimum viral load while administering it as a prophylactic treatment.

Fecal microbiota transplant is a strategy that consists of a stool derivative from healthy donors with infusion to patients. The injection believably constitutes more significant than 90% efficacy in the resolution of recurrent Clostridium difficile infections, which presents with more significant effect than antibiotic treatment alone. Safety concerns concerning the introduction of pathogens and exacerbating diseases have impacted a regulatory framework and stringent screening guidelines of donors. Also, the mitigation of safety concerns and increasing the treatment reliability of the microbiomes, the stakeholders focus on the determination of Determining the minimal microbiome subset of necessary for the achievement of therapeutic efficacy.

The fecal microbiota transplants are capable of proving the effectiveness of treating inflammatory bowel disease. Following the earlier trials, the disease has been processed successfully by the application of the operations. Additionally, recombinant bacterial therapy provides a cheaper and less invasive treatment for chronic conditions of inflammatory disease. As a result, Lactococcus lactis has been engineered successfully, secreting interleukin-10, which is critical for the anti-inflammatory cytokine, and effectively reduces pathology and suppresses the secretion of pro-inflammatory cytokine in patients. The expression microbiomes in other anti-inflammatory cytokines like transforming growth factor-β1, antitumor necrosis factor α nanobodies as well as factor keratinocyte growth factor-2 for tissue repair protects against the colitis. Besides, the lactic acid bacteria produce protease inhibitor Elafin, restoring the proteolytic homeostasis that the inhibitors disrupt in the colitis models, and those protecting against inflammation. Despite the preclinical researches, the approaches hardly show efficacy in humans, perhaps due to the challenge associated with the expression of the therapeutic molecules in the required levels and places timely.

Metabolic diseases, like obesity and diabetes, are also targeted by the delivery of engineered microbes into the host microbiota. In this context, E. coli is influenced by the synthesis of precursors lipids that suppress appetite, thus reducing obesity in the individuals feeding on a high diet of fats. However, GLP-1 is responsible for inducing the conversion of epithelial cells of the intestines in insulin-producing cells, expanding the number of the insulin-producing cells. At the same time, the hyperglycemia is reduced following the delivery of the Lactobacillus gasseri in the patients.

In addition to the conditions seeking for microbiota engineering for their treatment, hyperammonemia is another metabolic condition with evidence of the effectiveness of engineering the microbiota for its treatment. The bacterial ureases in the gut play a vital role I converting urea from the liver to ammonia and carbon dioxide. Hyperammonemia is a condition occurring as a result of too much ammonia accumulating systemically, and the condition causes neurotoxicity and encephalopathy, mostly in patients with liver disease. The situation reconstitutes manipulated the microbiota community for urea metabolism. The depletion of the endogenous microbiota and transplant of a microbial community that exhibits a low urease activity, however, has no immediate effect on the urease levels as they remain stable for a long time. The redefined microbiota enhances the chances of survival of the patient and reduces the cognitive defects of hyperammonemia in hepatic injuries. Thus, modification of an existing microbial community has a protective property against metabolic diseases. Furthermore, the engineering of microbes has impacted the reduction of systemic ammonia levels when administered to individuals. Luckily, companies are developing such therapies for application in clinical settings.

Subtractive therapies aiming at eliminating unhealthy members of the microbiome have also been used in treatments against microbial infections through the application of such mechanisms as antibiotics, chemicals, peptides, as well as bacteriophages. Antibiotic is an essential example of subtractive therapies, which often can kill most undesirable microbes outside the target population. The therapy results in the increased number of side effects, for instance, increased susceptibility to bacterial infections, including the Clostridium difficile. However, the subtractive therapies for the microbiome can be improved for specificity while targeting the activities.

A strategy for the highly specific subtractive therapies focuses on the use of phages, which are naturally viral parasites capable of infecting bacteria, which results in the death of the bacterial host. In contrast, the parasite tries to produce viral progeny. The increasingly dangerous antibiotic-resistant pathogens have led to rekindling interest in establishing phage therapy, particularly by considering that the phages often attack either one or a few bacterial cell types precisely, it can serve as the best antimicrobial agent. Ideally, the phages give natural shape to the host-associated populations of bacterial. Metagenomic researches concerning the fecal virome of healthy and diseased individuals reveal the diversity of phages, their variability, stability, inclusive of the changes in association with diets, IBD, and antibiotic therapies. The phages are observed to have a high variation in terms of viral community composition but a low diversity interpersonally owing to the temperate, potentially, dormant nature of the phase.

Besides, modification of the phages can be done for them to carry more or alternative functions in expanding their utility. Some phages have immunoglobulin-like protein domains on their capsids that play a critical role in enhancing association with mucus as a mechanism of localizing the phage in the particular body or instead for extending the residence time of the bacteria in the gut. The host range reprogramming also alters the bacterial targets and genes helps to insert genes to facilitate the elimination of the biofilms. Furthermore, phages have been applied successfully in the delivery of DNA to bacteria that can reverse antibiotic resistance or help in achieving nonspecific or sequence-specific activities of the antimicrobials towards the cells of the target. Other new tools like CRISPR-Cas genome editing and constructing methods, including Gibson and yeast assembly, facilitate the efforts for future engineering. Phages as therapeutics for microbiota-related diseases are representatives of promising areas concerning investigations, and they are appropriate tools for altering microbial communities to ensure a systematic probing of the populations, allowing for discoveries as well as validations while studying health and the microbiome.

In conclusion, the researchers have fastened the process of developing microbiota-based therapeutics due to the progressive synthetic biology and excellent understanding of the host associations of the microbial consortia, despite the increased number of challenges arising. In contrast, the researchers attempt to bring the idea in clinical practice. However, most advancements in the therapy of microbiome have been validated through the use of rodent models, although the challenge comes in a while generalizing the results to humans, such that they can be applied clinically. Also, there is a relevance of developing the autonomous cellular therapies fully that requires relevant biosensors and robust genetic circuits. Most importantly, the translation of primary research outcomes to clinical applications is dependent on regulatory frameworks that are set for addressing the unique issues with living therapeutics.