Hybrid de novo and haplotype-resolved genome assembly of Vechur cattle - elucidating genetic variation.

Cattle contribute to the nutritional needs and economy of a place. The performance and fitness of cattle depend on the response and adaptation to local climatic conditions. Genomic and genetic studies are important for advancing cattle breeding, and availability of relevant reference genomes is essential. In the present study, the genome of a Vechur calf was sequenced on both short-read Illumina and long-read Nanopore sequencing platforms. The hybrid de novo assembly approach was deployed to obtain an average contig length of 1.97 Mbp and an N50 of 4.94 Mbp. By using a short-read genome sequence of the corresponding sire and dam, a haplotype-resolved genome was also assembled. In comparison to the taurine reference genome, we found 28,982 autosomal structural variants and 16,926,990 SNVs, with 883,544 SNVs homozygous in the trio samples. Many of these SNPs have been reported to be associated with various QTLs including growth, milk yield, and milk fat content, which are crucial determinants of cattle production. Furthermore, population genotype data analysis indicated that the present sample belongs to an Indian cattle breed forming a unique cluster of Bos indicus. Subsequent FST analysis revealed differentiation of the Vechur cattle genome at multiple loci, especially those regions related to whole body growth and cell division, especially IGF1, HMGA2, RRM2, and CD68 loci, suggesting a possible role of these genes in its small stature and better disease resistance capabilities in comparison with the local crossbreeds. This provides an opportunity to select and engineer cattle breeds optimized for local conditions.

Cord blood platelet rich plasma (PRP) as a potential alternative to autologous PRP for allogenic preparation and regenerative applications.

As an abundant supplier of growth factors, chemokines and other bioactive molecules, platelet rich plasma (PRP) become a leading therapy for tissue regeneration. The PRP therapy is an inexpensive and feasible source of growth factor compared to commercial products however, the better source of platelets is the major challenge. Many researchers are skeptical about cord blood as an alternative source for the allogenic preparation of PRP. In the present study, we have compared adult peripheral and cord blood PRP for their regenerative capacity and immuno-modulatory nature. ELISA data indicates that the cord PRP contained a considerably higher amount of growth factors compared to adult PRP. In-vitro results indicate a significant increase in cell proliferation and migration with cord PRP treatment. The immunomodulatory evaluation shows cord blood PRP has better potential in switching activated macrophages to anti-inflammatory markers when compared with adult PRP, as well as the cytokines production indicates a significant reduction in the release of IFN-γ in cord PRP treatment. The study shows the beneficial effects of using cord blood PRP over adult PRP however, future studies are required to validate cord blood PRP as a permanent source for regenerative therapy.

A Novel Protozoa Parasite-Derived Protein Adjuvant Is Effective in Immunization with Cancer Cells to Activate the Cancer-Specific Protective Immunity and Inhibit the Cancer Growth in a Murine Model of Colorectal Cancer.

Cancer-specific CD8+ cytotoxic T cells play important roles in preventing cancer growth, and IFN-γ, in addition to IL-12 and type I interferon, is critical for activating CD8+ cytotoxic T cells. We recently identified the capability of the amino-terminus region of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, an intracellular protozoan parasite, to activate IFN-γ production of microglia, a tissue-resident macrophage population. Therefore, in the present study, we examined whether recombinant GRA6Nt protein (rGRA6Nt) functions as an effective adjuvant to potently activate cancer-specific protective immunity using a murine model of MC38 colorectal cancer (CRC). When mice were immunized with non-replicable (either treated with mitomycin C or irradiated by X-ray) MC38 CRC cells in combination with rGRA6Nt adjuvant and received a challenge implantation of replication-capable MC38 tumor cells, those mice markedly inhibited the growth of the implanted tumors in association with a two-fold increase in CD8+ T cell density within the tumors. In addition, CD8+ T cells of the immunized mice secreted significantly increased amounts of granzyme B, a key mediator of the cytotoxic activity of CD8+ T cells, and IFN-γ in response to MC38 CRC cells in vitro when compared to the T cells from unimmunized mice. Notably, the protective effects of the immunization were specific to MC38 CRC cells, as the immunized mice did not exhibit a significantly inhibited growth of EL4 lymphoma tumors. These results indicate that rGRA6Nt is a novel and effective protein adjuvant when used in immunizations with non-replicable cancer cells to potently activate the protective immunity specifically against the cancer cells employed in the immunization.

Dense granule protein 3 of Toxoplasma gondii plays a crucial role in the capability of the tissue cysts of the parasite to persist in the presence of anti-cyst CD8+ T cells during the chronic stage of infection.

Toxoplasma gondii establishes chronic infection by forming tissue cysts, and this chronic infection is one of the most common parasitic infections in humans. Our recent studies revealed that whereas CD8+ T cells of genetically resistant BALB/c mice have the capability to remove the tissue cysts of the parasite through their perforin-mediated activities, small portions of the cysts are capable of persisting in the presence of the anti-cyst CD8+ T cells. It is currently unknown how those small portions of the cysts resist or escape the T-cell immunity and persist in the hosts. In the present study, we discovered that the cysts, which persisted in the presence of the perforin-mediated CD8+ T-cell immunity, have significantly greater mRNA levels for four dense granule proteins, GRA1, GRA2, GRA3, and GRA7, and one rhoptry protein, ROP35, than the total population of the cysts present in the absence of the T cells. In addition, increased levels of mRNA for GRA1, GRA3, and ROP35 in the cysts significantly correlated with their successful persistence through the condition in which greater degrees of reduction of the cyst burden occurred through anti-cyst CD8+ T cells. In addition, GRA3-deficient T. gondii displayed significantly enhanced elimination of the cysts by anti-cyst CD8+ T cells when compared to the wild-type parasite. These results indicate that GRA3 is a key molecule that mediates in the capability of T. gondii cysts to persist by resisting or evading the anti-cyst activity of CD8+ T cells during the later stage of infection.

Immunization with the amino-terminus region of dense granule protein 6 (GRA6) of Toxoplasma gondii activates CD8+ cytotoxic T cells capable of removing tissue cysts of the parasite through antigen presentation by human HLA-A2.1.

CD8+ T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino-terminus region (aa 41-152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8+ T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by a transfer of the HLA-A2.1-transgenic CD8+ immune T cells required an expression of HLA-A2.1 in the recipient NSG mice. Thus, antigen presentation of GRA6Nt by human HLA-A2.1is able to activate anti-cyst CD8+ T cells that eliminate T. gondii cysts through antigen presentation by human HLA-A2.1.

Biomaterial-based platforms for modulating immune components against cancer and cancer stem cells.

Immunotherapy involves the therapeutic alteration of the patient's immune system to identify, target, and eliminate cancer cells. Dendritic cells, macrophages, myeloid-derived suppressor cells, and regulatory T cells make up the tumor microenvironment. In cancer, these immune components (in association with some non-immune cell populations like cancer-associated fibroblasts) are directly altered at a cellular level. By dominating immune cells with molecular cross-talk, cancer cells can proliferate unchecked. Current clinical immunotherapy strategies are limited to conventional adoptive cell therapy or immune checkpoint blockade. Targeting and modulating key immune components presents an effective opportunity. Immunostimulatory drugs are a research hotspot, but their poor pharmacokinetics, low tumor accumulation, and non-specific systemic toxicity limit their use. This review describes the cutting-edge research undertaken in the field of nanotechnology and material science to develop biomaterials-based platforms as effective immunotherapeutics. Various biomaterial types (polymer-based, lipid-based, carbon-based, cell-derived, etc.) and functionalization methodologies for modulating tumor-associated immune/non-immune cells are explored. Additionally, emphasis has been laid on discussing how these platforms can be used against cancer stem cells, a fundamental contributor to chemoresistance, tumor relapse/metastasis, and failure of immunotherapy. Overall, this comprehensive review strives to provide up-to-date information to an audience working at the juncture of biomaterials and cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cancer immunotherapy possesses incredible potential and has successfully transitioned into a clinically lucrative alternative to conventional anti-cancer therapies. With new immunotherapeutics getting rapid clinical approval, fundamental problems associated with the dynamic nature of the immune system (like limited clinical response rates and autoimmunity-related adverse effects) have remained unanswered. In this context, treatment approaches that focus on modulating the compromised immune components within the tumor microenvironment have garnered significant attention amongst the scientific community. This review aims to provide a critical discussion on how various biomaterials (polymer-based, lipid-based, carbon-based, cell-derived, etc.) can be employed along with immunostimulatory agents to design innovative platforms for selective immunotherapy directed against cancer and cancer stem cells.

Human MHC class I molecule, HLA-A2.1, mediates activation of CD8+ T cell IFN-γ production and the T cell-dependent protection against reactivation of cerebral Toxoplasma infection.

To examine whether the HLA-A2.1, one of the most common MHC class I molecules in humans, activates the protective immunity against reactivation of cerebral infection with Toxoplasma gondii, HLA-A2.1-transgenic and wild-type (WT) mice were infected and treated with sulfadiazine to establish chronic infection in their brains. One month after discontinuation of sulfadiazine, which initiates reactivation of the infection, mRNA levels for tachyzoite (the acute stage form)-specific SAG1 and numbers of the foci associated tachyzoites were significantly less in the brains of the HLA-A2.1-transgenic than WT mice. Greater numbers of IFN-γ-producing CD8+ T cells were detected in the spleens of infected transgenic than WT mice, and CD8+ T cells from the former produced markedly greater amounts of IFN-γ than the T cells from the latter in response to tachyzoite antigens in vitro. When their CD8+ T cells were systemically transferred to infected immunodeficient NSG mice expressing the HLA-A2.1, the CD8+ T cells from HLA-A2.1-transgenic mice inhibited reactivation of the cerebral infection in the recipients more efficiently than did the WT T cells. Furthermore, the inhibition of reactivation of the infection by CD8+ T cells from the transgenic mice was associated with increased cerebral expression of IFN-γ and effector molecules against tachyzoites in the recipients when compared to the WT CD8+ T cell recipients. Thus, the human HLA-A2.1 is able to effectively activate IFN-γ production of CD8+ T cells against T. gondii tachyzoites and confer a potent protection against reactivation of cerebral infection with this parasite through the CD8+ T cells activation.

Biomimicking nanofibrous gelatin microspheres recreating the stem cell niche for their ex-vivo expansion and in-vivo like differentiation for injectable stem cell transplantation.

Stem cells based novel treatment modality for degenerative and immune dysfunction diseases created a huge demand of suitable carriers to support ex-vivo production of quality stem cells, and effective in-vivo transplantation of stem cells and their fate. In spite of promising candidature of nanofibrous microspheres (NFM) to recreate native stem cell niches to be used for possible scaling-up for ex-vivo stem cells expansion, it remains fairly unexplored. A systematic study on the stem cell-NFM interaction comparative with commercial microspheres (CM) has been performed for the first time. Gelatin NFM with variable physicochemical properties such as size, surface properties, surface chemistry, and variable degradability were prepared using microemulsion coupled with thermally induced phase separation (TIPS) method. Effect of physicochemical properties of NFM and their cellular interaction such as binding, morphology, metabolic activity and proliferation studies were performed using human bone marrow-derived mesenchymal stem cells (hBMSCs), human dental follicle stem cells (hDFSCs) and human gingival fibroblast (HGF) cells and compared with the commercial and solid microspheres. Gelatin NFM supports excellent cell binding, proliferation, metabolic activities and chemical cues specific differentiation. All out-turns indicate that NFM stand to be an outstanding candidate for ex-vivo cells' expansion and injectable carriers for stem cell transplantation.

Deficiency in indoleamine-2, 3-dioxygenase induces upregulation of guanylate binding protein 1 and inducible nitric oxide synthase expression in the brain during cerebral infection with Toxoplasma gondii in genetically resistant BALB/c mice but not in genetically susceptible C57BL/6 mice.

We examined the roles of indoleamine-2, 3-dioxygenase 1 (IDO1) in controlling cerebral Toxoplasma gondii infection in both genetically resistant and susceptible strains of mice. In susceptible C57BL/6 mice, IDO expression was immunohistochemically detected only in a minority (22.5%) of tachyzoite-infected cells in their brains during the later stage of infection. When C57BL-6-background IDO1-deficient (IDO1-/-) mice were infected, their cerebral tachyzoite burden was equivalent to those of wild-type (WT) animals. In contrast, in resistant BALB/c mice, IDO expression was detected in a majority (84.0%) of tachyzoite-infected cerebral cells. However, tachyzoite burden in BALB/c-background IDO1-/- mice remained as low as that of WT mice, which was 78 times less than those of C57BL/6 mice. Of interest, IDO1-/- mice of only resistant BALB/c-background had markedly greater cerebral expressions of two other IFN-γ-mediated effector molecules, guanylate binding protein 1 (Gbp1) and nitric oxide synthase 2 (NOS2), than their WT mice. Therefore, it would be possible that IDO1 deficiency was effectively compensated by the upregulated expression of Gbp1 and NOS2 to control cerebral tachyzoite growth in genetically resistant BALB/c mice, whereas IDO1 did not significantly contribute to controlling cerebral tachyzoite growth in genetically susceptible C57BL/6 mice because of its suppressed expression in infected cells.

Co-Administration of Aluminium Hydroxide Nanoparticles and Protective Antigen Domain 4 Encapsulated Non-Ionic Surfactant Vesicles Show Enhanced Immune Response and Superior Protection against Anthrax.

Aluminium salts have been the adjuvant of choice in more than 100 licensed vaccines. Here, we have studied the synergistic effect of aluminium hydroxide nanoparticles (AH np) and non-ionic surfactant-based vesicles (NISV) in modulating the immune response against protective antigen domain 4 (D4) of Bacillus anthracis. NISV was prepared from Span 60 and cholesterol, while AH np was prepared from aluminium chloride and sodium hydroxide. AH np was co-administered with NISV encapsulating D4 (NISV-D4) to formulate AHnp/NISV-D4. The antigen-specific immune response of AHnp/NISV-D4 was compared with that of commercial alhydrogel (alhy) co-administered with NISV-D4 (alhydrogel/NISV-D4), NISV-D4, AHnp/D4, and alhydrogel/D4. Co-administration of NISV-D4 with AH np greatly improved the D4-specific antibody titer as compared to the control groups. Based on IgG isotyping and ex vivo cytokine analysis, AHnp/NISV-D4 generated a balanced Th1/Th2 response. Furthermore, AH np/NISV-D4 showed superior protection against anthrax spore challenge in comparison to other groups. Thus, we demonstrate the possibility of developing a novel combinatorial nanoformulation capable of augmenting both humoral and cellular response, paving the way for adjuvant research.

Crystalline and Amorphous Preparation of Aluminum Hydroxide Nanoparticles Enhances Protective Antigen Domain 4 Specific Immunogenicity and Provides Protection Against Anthrax.

INTRODUCTION: Aluminum salts, although they have been used as adjuvants in many vaccine formulations since 1926, exclusively induce a Th2-biased immune response, thereby limiting their use against intracellular pathogens like Mycobacterium tuberculosis. METHODS AND RESULTS: Herein, we synthesized amorphous and crystalline forms of aluminum hydroxide nanoparticles (AH nps) of 150-200 nm size range. Using Bacillus anthracis protective antigen domain 4 (D4) as a model antigen, we demonstrated that both amorphous and crystalline forms of AH nps displayed enhanced antigen D4 uptake by THP1 cells as compared to commercial adjuvant aluminum hydroxide gel (AH gel). In a mouse model, both amorphous and crystalline AH nps triggered an enhanced D4-specific Th2- and Th1-type immune response and conferred superior protection against anthrax spore challenge as compared to AH gel. Physicochemical characterization of crystalline and amorphous AH nps revealed stronger antigen D4 binding and release than AH gel. CONCLUSION: These results demonstrate that size and crystallinity of AH nps play important roles in mediating enhanced antigen presenting cells (APCs) activation and potentiating a strong antigen-specific immune response, and are critical parameters for the rational design of alum-based Th1-type adjuvant to induce a more balanced antigen-specific immune response.

Single-dose Ag85B-ESAT6-loaded poly(lactic-co-glycolic acid) nanoparticles confer protective immunity against tuberculosis.

BACKGROUND: Bacillus Calmette-Guérin, the attenuated strain of Mycobacterium bovis, remains the only available vaccine against tuberculosis (TB). However, its ineffectiveness in adults against pulmonary TB and varied protective efficacy (0-80%) speak to an urgent need for the development of an improved and efficient TB vaccine. In this milieu, poly(lactic-co-glycolic acid) (PLGA), is a preferential candidate, due to such properties as biocompatibility, targeted delivery, sustained antigen release, and atoxic by-products. METHODS: In this study, we formulated PLGA nanoparticles (NPs) encapsulating the bivalent H1 antigen, a fusion of Mycobacterium tuberculosis (Mtb) Ag85B and ESAT6 proteins, and investigated its role in immunomodulation and protection against Mtb challenge. Using the classical water-oil-water solvent-evaporation method, H1-NPs were prepared, with encapsulation efficiency of 86.1%±3.2%. These spherical NPs were ~244.4±32.6 nm in diameter, with a negatively charged surface (ζ-potential -4±0.6 mV). RESULTS: Under physiological conditions, NPs degraded slowly and the encapsulated H1 antigen was released over a period of weeks. As a proof-of-concept vaccine candidate, H1 NPs were efficiently internalized by the THP-1 human macrophages. Six weeks after a single-dose vaccination, H1 NP-immunized C57BL/6J mice showed significant increase in the production of total serum IgG (P<0.0001) and its isotypes compared to H1 alone, IgG2a being the predominant one, followed by IgG1. Further, the cytokine-release profile of antigen-stimulated splenocyteculture supernatant indicated a strong TH1-biased immunoresponse in H1 NP-vaccinated mice, with ~6.03- and ~2.8-fold increase in IFNγ and TNFα cytokine levels, and ~twofold and 1.6 fold increase in IL4 and IL10 cytokines, respectively, compared to H1 alone-immunized mice. In protection studies, H1 NP-vaccinated mice displayed significant reductions in lung and spleen bacillary load (P<0.05) at 5-week post-Mtb H37Rv challenge and prolonged survival, with a mean survival time of 177 days, compared to H1 alone-vaccinated mice (mean survival time 80 days). CONCLUSION: Altogether, our findings highlight the significance of the H1-PLGA nanoformulation in terms of providing long-term protection in mice with a single dose.

A niosome formulation modulates the Th1/Th2 bias immune response in mice and also provides protection against anthrax spore challenge.

INTRODUCTION: In this study, we have investigated the immunogenicity and protective efficacy of a niosomal formulation encapsulating protective antigen (PA) and PA domain 4 (D4) of Bacillus anthracis. METHODS: Nonionic surfactant-based vesicles (NISV) + PA and NISV + D4 were prepared from span-60 and cholesterol by reverse-phase evaporation method and were evaluated for in vitro characteristics and immunological studies. RESULTS: Particle characterization using transmission electron microscopy and atomic force microscopy analysis showed that the niosomal formulation was spherical in shape. The entrapment efficiency values were calculated to be 58.5% and 44.75% for PA and D4, respectively. Confocal microscopy and flow cytometry studies showed an enhanced uptake of antigen in THP1 macrophages by niosome as compared to antigen only. An in vitro release assay showed a burst release of antigen from niosome within 24 hours followed by a gradual release for 144 hours. Immunological studies showed that both PA- and D4-encapsulated niosome elicited a robust IgG titer. Antibody isotyping and cytokine profile showed that NISV + PA and NISV + D4 enhanced both Th1 and Th2 responses in mice, suggesting a mixed Th1/Th2 response. Both NISV + PA and NISV + D4 elicited high levels of anti-inflammatory cytokine interleukin-10 with low levels of pro-inflammatory cytokine tumor necrosis factor-α, suggesting the anti-inflammatory property of niosome. Both the niosomal formulations were also able to confer protection against BA infection as compared to only PA and D4. CONCLUSION: PA and D4 encapsulated NISV formulation could modulate both the Th1 and Th2 adaptive immune system and was found to be a better prophylactic against anthrax.

Adjuvant Potential of Poly-α-l-Glutamine from the Cell Wall of Mycobacterium tuberculosis.

Novel adjuvants are in demand for improving the efficacy of human vaccines. The immunomodulatory properties of Mycobacterium tuberculosis cell wall components have been highlighted in the formulation of complete Freund's adjuvant (CFA). We have explored the adjuvant potential of poly-α-l-glutamine (PLG), a lesser-known constituent of the pathogenic mycobacterial cell wall. Immune parameters indicated that the adjuvant potency of PLG was statistically comparable to that of CFA and better than that of alum in the context of H1 antigen (Ag85B and ESAT-6 fusion). At 1 mg/dose, PLG augmented the immune response of Ag85B, BP26, and protective antigen (PA) by increasing serum antibodies and cytokines in the culture supernatant of antigen-stimulated splenocytes. PLG modulated the humoral response of vaccine candidate ESAT-6, eliciting significantly higher levels of total IgG and isotypes (IgG1, IgG2a, and IgG2b). Additionally, the splenocytes from PLG-adjuvanted mice displayed a robust increase in the Th1-specific gamma interferon, tumor necrosis factor alpha, interleukin-2 (IL-2), Th2-specific IL-6 and IL-10, and Th17-specific IL-17A cytokines upon antigenic stimulation. PLG improved the protective efficacy of ESAT-6 by reducing bacillary load in the lung and spleen as well as granuloma formation, and it helped in maintaining vital health parameters of mice challenged with M. tuberculosis The median survival time of PLG-adjuvanted mice was 205 days, compared to 146 days for dimethyl-dioctadecyl ammonium bromide-monophosphoryl lipid A (DDA-MPL)-vaccinated groups and 224 days for Mycobacterium bovis BCG-vaccinated groups. PLG enhanced the efficiency of the ESAT-6 vaccine to the level of BCG and better than that of DDA-MPL (P < 0.05), with no ill effect in C57BL/6J mice. Our results propose that PLG is a promising adjuvant candidate for advanced experimentation.

Trimethyl Chitosan Nanoparticles Encapsulated Protective Antigen Protects the Mice Against Anthrax.

Anthrax is an era old deadly disease against which there are only two currently available licensed vaccines named anthrax vaccine adsorbed and precipitated (AVP). Though they can provide a protective immunity, their multiple side-effects owing to their ill-defined composition and presence of toxic proteins (LF and EF) of Bacillus anthracis, the causative organism of anthrax, in the vaccine formulation makes their widespread use objectionable. Hence, an anthrax vaccine that contains well-defined and controlled components would be highly desirable. In this context, we have evaluated the potential of various vaccine formulations comprising of protective antigen (PA) encapsulated trimethyl-chitosan nanoparticles (TMC-PA) in conjunction with either CpG-C ODN 2395 (CpG) or Poly I:C. Each formulation was administered via three different routes, viz., subcutaneous (SC), intramuscular (IM), and intraperitoneal in female BALB/c mice. Irrespective of the route of immunization, CpG or Poly I:C adjuvanted TMC-PA nanoparticles induced a significantly higher humoral response (total serum IgG and its isotypes viz., IgG1, IgG2a, and IgG2b), compared to their CpG or Poly I:C PA counterparts. This clearly demonstrates the synergistic behavior of CpG and Poly I:C with TMC nanoparticles. The adjuvant potential of TMC nanoparticles could be observed in all the three routes as the TMC-PA nanoparticles by themselves induced IgG titers (1-1.5 × 105) significantly higher than both CpG PA and Poly I:C PA groups (2-8 × 104). The effect of formulations on T-helper (Th) cell development was assessed by quantifying the Th1-dependant (TNF-α, IFN-γ, and IL-2), Th2-dependant (IL-4, IL-6, and IL-10), and Th17-type (IL-17A) cytokines. Adjuvanation with CpG and Poly I:C, the TMC-PA nanoparticles triggered a Th1 skewed immune response, as suggested by an increase in the levels of total IgG2a along with IFN-γ cytokine production. Interestingly, the TMC-PA group showed a Th2-biased immune response. Upon challenge with the B. anthracis Ames strain, CpG and Poly I:C adjuvanted TMC-PA nanoparticles immunized via the SC and IM routes showed the highest protective efficacy of ~83%. Altogether, the results suggest that CpG or Poly I:C adjuvanted, PA-loaded TMC nanoparticles could be used as an effective, non-toxic, second generation subunit-vaccine candidate against anthrax.

Influence of diet and dietary nanoparticles on gut dysbiosis.

Human gut comprises of a huge mixture of microorganisms as they had co-existed for millions of years. The change in co-existence of microbial genera leads to dysbiosis, which creates several disorders in humans. Diet and diet associated agents can have a considerable influence on host health by regulating the gut microbiome, which can thereby maintain the homeostasis of the gut. Analysis of the gut microbiome and the agents that can have an influence on the gut need a profound understanding, which is the need of the hour. The current review therefore focuses on the influence of diet and dietary nanoparticles on the gut microbiota and their positive or adverse effect.