Haplotype-based breeding: A new insight in crop improvement.

Haplotype-based breeding (HBB) is one of the cutting-edge technologies in the realm of crop improvement due to the increasing availability of Single Nucleotide Polymorphisms identified by Next Generation Sequencing technologies. The complexity of the data can be decreased with fewer statistical tests and a lower probability of spurious associations by combining thousands of SNPs into a few hundred haplotype blocks. The presence of strong genomic regions in breeding lines of most crop species facilitates the use of haplotypes to improve the efficiency of genomic and marker-assisted selection. Haplotype-based breeding as a Genomic Assisted Breeding (GAB) approach harnesses the genome sequence data to pinpoint the allelic variation used to hasten the breeding cycle and circumvent the challenges associated with linkage drag. This review article demonstrates ways to identify candidate genes, superior haplotype identification, haplo-pheno analysis, and haplotype-based marker-assisted selection. The crop improvement strategies that utilize superior haplotypes will hasten the breeding progress to safeguard global food security.

Profiling of Groundnut bud necrosis orthotospovirus-responsive microRNA and their targets in tomato based on deep sequencing.

Tomato, an extensively cultivated vegetable crop produces miRNAs in response to infection with Groundnut bud necrosis orthotospovirus, a viral pathogen causing significant economic losses. High-throughput miRNA sequencing was performed on tomato leaves inoculated with GBNV and mock-inoculated leaves as controls. Analysis revealed 73 known miRNAs belonging to 24 miRNA families, with variable expression levels. Interestingly, 39 miRNAs were upregulated, and 34 were downregulated in response to GBNV infection. Stem-loop quantitative reverse transcription PCR validated the differential expression of selected miRNAs. Additionally, 30 miRNA encoded proteins were identified to be involved in disease resistance and susceptibility. The miRNA-target interactions were found to play significant roles in cellular and metabolic activities, as well as modulating signaling pathways during the plant-virus interaction. The findings shed light on the intricate regulatory network of miRNAs in tomato response to viral infection and may contribute to developing strategies for improving crop protection against viral diseases.

Emerging challenges in the management of Orthotospoviruses in Indian agriculture.

Orthotospoviruses, a genera of negative-sense ssRNA viruses transmitted by thrips, have gained significant attention in recent years due to their detrimental impact on diverse crops, causing substantial economic losses and posing threats to food security. Orthotospoviruses are characterised by a wide range of symptoms in plants, including chlorotic/necrotic spots, vein banding, and fruit deformation. Seven species, including four definite and three tentative species in the genus Orthotospovirus, have so far been documented on the crops of the Indian subcontinent. Management of Orthotospoviruses under field conditions is challenging since they have a wide host range, adaptation to versatile environmental conditions, a lack of promising resistance sources, and the ubiquitous nature of thrips and their transmission through a propagative manner. Our present review elucidates the significance, molecular biology and evolutionary relationship of Orthotospoviruses; vector population; and possible management strategies for Orthotospoviruses and their vectors in the scenario of the Indian subcontinent.

A distinct strain of tomato leaf curl New Delhi virus that causes mosaic disease in ash gourd and other cucurbitaceous crops.

Ash gourd (Benincasa hispida) is a cucurbitaceous crop cultivated as an edible vegetable rich in vitamins, minerals, dietary fibers and antioxidants. In a field survey conducted in the Udumalpet region of Tamil Nadu during 2019, the incidence of mosaic disease on ash gourd crop was observed to be 75%. The DNA-A and DNA-B components of begomovirus genome have been identified as associated with this disease. Both the cloned DNA-A and DNA-B genomic components shared highest pairwise sequence identities with the isolates of tomato leaf curl New Delhi virus (ToLCNDV), a bipartite begomovirus. Recombinant analysis showed that both the components are possibly evolved through intra-species recombination between ToLCNDV isolates. Tomato leaf curl Bangladesh betasatellite (ToLCBB) is not naturally associated with this sample. The results of infectivity studies on ash gourd and other cucurbitaceous crops demonstrates the Koch's postulates, when co-inoculation of DNA-A and DNA-B of ToLCNDV was undertaken. However, the inoculation of non-cognate ToLCBB along with DNA-A and DNA-B enhances the symptom expression and reduces the time taken for symptom development. Thus, Koch's postulates were proved for these virus complexes on cucurbitaceous crops. Furthermore, an enhanced accumulation of DNA-A component was detected in the cucurbits co-inoculated with ToLCNDV and ToLCBB. This report highlights the importance of investigating the spread of these disease complexes with other cucurbitaceous crops in India.

Exogenous delivery of dsRNA for management of mungbean yellow mosaic virus on blackgram.

MAIN CONCLUSION: Exogenous application of dsRNA molecules targeting MYMV genes offers a promising approach to effectively mitigate yellow mosaic disease in blackgram, demonstrating potential for sustainable plant viral disease management. The exogenous application of double-stranded RNA (dsRNA) molecules to control plant viral diseases is gaining traction due to its advantages over conventional methods, such as target specificity, non-polluting nature, and absence of residue formation. Furthermore, this approach does not involve genome modification. In this study, dsRNA molecules targeting the coat protein gene (dsCP) and replication initiator protein gene (dsRep) of mungbean yellow mosaic virus (MYMV) were synthesised using an in vitro transcription method. To evaluate the effectiveness of dsRNA treatment, blackgram plants exhibiting MYMV symptoms at the first trifoliate stage were subjected to exogenous application of dsRNA. Second, third, and fourth trifoliate leaves, which emerged at 7, 15, and 21 days after dsRNA application, respectively, were monitored for MYMV symptoms. Remarkably, a significant reduction in yellow mosaic disease (YMD) symptoms was observed in the newly emerged trifoliate leaves of MYMV-infected blackgram plants after treatment with dsRNA targeting both gene regions. This reduction was evident as a decrease in the intensity of yellow mosaic coverage on the leaf lamina compared to control. dsCP effectively reduced the MYMV titre in the treated plants for up to 15 days. However, dsRep demonstrated greater efficiency in conferring resistance to MYMV at 15 days post-application. These findings were supported by quantitative real-time PCR analysis, where the observed Ct values for DNA extracted from dsRep-treated plants were significantly higher compared to the Ct values of DNA from dsCP-treated plants at 15 days post-application. Similarly, higher viral copy numbers were observed in dsCP-treated plants 15 days after dsRNA treatment, in contrast to plants treated with dsRep.

Nematicidal Properties of Chitosan Nanoformulation.

Chitosan is the second most abundant bio-polymer available in the world, second only to cellulose. It is found in crustaceous shells, e.g., those of crabs, shrimps, prawns, and fungi, as well as insect exoskeletons. The use of nanoformulations for the management of pests and diseases is receiving increased interest with the advancement of nanotechnology. Here, chitosan nanospheres were obtained from chitosan using the ionic gelation technique. The nanoformulations obtained were characterized using a particle size analyzer, Fourier transform infrared spectroscopy, and a transmission electron microscope. The efficacy of chitosan nanospheres in suppressing the root-knot nematode Meloidogyne incognita was studied. The particle size of nanospheres formulated for this study was 380.2 nm, with a polydispersity index (PI) of 0.4 and Zeta potential of 45.7 or 50.9 mV at pH 5.2. The chitosan nanospheres were spherical and the particles did not agglomerate. FTIR spectra of the chitosan nanospheres peaked at 3334 cm-1, thereby indicating the stretching of the OH and NH group. In In-vitro studies, chitosan nanospheres showed significant nematicidal activity against M. incognita. Under pot culture conditions, chitosan nanospheres (1%- active compound chitosan) at 2ml/plant decreased the nematode population in roots or soil. Compared to the control, the number of galls was reduced by 83.68%, the number of egg masses by 83.85%, the number of adult females by 66.56%, and the number of second-stage juveniles by 73.20%. In a field experiment, application of chitosan nanospheres (1%) was followed by a 18.75% increase in fruit yield compared to the non-treated control.

Engineering resistance against Cucumber mosaic virus in Nicotiana tabacum through virus derived transgene expressing hairpin RNA.

Cucumber mosaic virus (CMV) is the one of notorious virus known for its ubiquitous nature and causes substantial yield loss worldwide. The resistance against the Cucumber mosaic virus (CMV) was envisaged in Nicotiana tabacum transgenic lines by introducing viral gene fragments. The chimeric hairpin RNA constructs incorporating 401 bp of coat protein, 411 bp of replicase protein and 361 bp of 2b gene were developed respectively and transformed into N. tabacum. The regenerated transgenic lines introduced with inverted repeats of CMV gene fragments exhibited enhanced resistance against CMV. The preliminary molecular screening and qPCR confirmed the integration of transgene in the transgenic lines. The spectrum of resistance in transgenic lines was evaluated by challenge inoculation with CMV and the resistance was determined through DAC-ELISA. The complete resistance was achieved in the hpRNA-CP transformant with a very low titre (0.029) of CMV followed by hpRNA-REP (0.099) with no symptoms. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03576-1.

Utilization of non-vascularized bone graft with regional flap as an alternative for facial reconstruction.

Mandibular resections decision is one of the most important steps in oral cavity malignant or nonmalignant lesions associated with the mandible. The role of mandibular reconstruction is not only for cosmesis, but it is also indicated for functional rehabilitation such as swallowing, phonetics, and for facial symmetrical. Even though the free tissue transfer is considered a gold standard for mandibular reconstruction, the importance of nonvascularized bone grafts (NVBGs) such as fibula, calvarium, rib, sternum, and iliac are still persisting in mandibulectomies condition like patient who have not taken radiotherapy or not willing to undergo radiotherapy or not fit for free tissue transfer and provides a good contour of mandibular replacement. The success rate of NVBG depends upon patient selection, preoperative planning, and meticulous nursing care. Addition to NVBG, regional flaps such as pectoralis major myocutaneous (PMMC) flap will help in soft-tissue replacement of the defect as well as it will help in the situation where primary closure and airtight closure is not possible. This case report will discuss in detail about the management of anterior segmental mandibulectomy due to oncological resection and reconstruction with NVBG with fibula and PMMC.

Molecular epidemiology on seasonal variation of yellow mosaic disease incidence in blackgram (Vigna mungo L. Hepper) with its vector Bemisia tabaci.

The yellow mosaic disease (YMD) of blackgram caused by Mungbean yellow mosaic virus has emerged as a serious threat to grain legume production, especially in Southeastern Asia. Seasonal incidence of YMD with its vector population was assessed in three different agroclimatic zones of Tamil Nadu in India for three consecutive cropping seasons namely, Rabi 2018 (October-December), Summer 2019 (March-May), and Kharif 2019 (June-August) at three different time intervals viz., 20, 40, and 60 days after sowing (DAS). For all three seasons, disease incidence and whitefly count were recorded for a resistant and susceptible variety of blackgram in fields without any vector control intervention. The highest disease incidence (87%) was observed in the Panpozhi location during the summer season followed by Vamban and Coimbatore locations. The whitefly count was made through both visual count and yellow sticky traps. The whitefly population was highest at 20 DAS and decreased with the increasing age of crop for all the three locations assessed. Molecular epidemiology was analyzed by determining latent infection of mungbean yellow mosaic virus (MYMV) using molecular diagnosis. Latent infection was found to be well pronounced in the Coimbatore location during the Kharif season, where the crop was asymptomatic in both the resistant and susceptible varieties for all the three time periods assessed. The latent infection of MYMV observed in Coimbatore and Vamban ranged from 16.6 to 83.3% in both resistant and susceptible varieties for all three seasons. In Panpozhi, the latent infection of MYMV ranged from 16.6 to 66.6% for the susceptible variety (CO-5) for all three seasons observed. However, in the Panpozhi location, the resistant variety (VBN-8) failed to record any latent infection.

Preponderance of mixed infection of Cucumber mosaic virus and Candidatus Phytoplasma australasia on brinjal in India.

Cucumber mosaic virus (CMV) has broad host range by infecting major stable food crops and causes heavy loss especially in brinjal. In major brinjal growing tracts of Tamil Nadu, Krishnagiri recorded the highest combined infection of CMV and Candidatus Phytoplasma australasia (Ca. P. australasia) with 26%. The symptoms ranged from mild to severe mosaic, mottling, filiformity of leaves and little leaf. The virus was successfully transmitted to cowpea cv. CO7 and ridge gourd through mechanical inoculation and the presence of virus was detected both by DAC-ELISA and RT-PCR. Electron microscopy of CMV exemplified isometric particles with 28-35 nm under TEM and phytoplasma with 700-820 nm in SEM analysis. Among the different test hosts, Luffa acutangula was found to be the best indicator host for brinjal CMV isolate as it requires shorter period (4-5DPI) to express symptoms with good virus titer (A405nm 2.318). The genome characterization of CMV TNB isolate revealed that the RNA1, RNA2 and RNA3 have 97, 96 and 99% homology with other 1B sub group CMV isolates, respectively. Recombination analysis of RNA2 of CMV TNB has tomato Egyptian isolate (KT921315) as major parent and black pepper Indian isolate (KU947030) as minor parent at the conserved region (52-805nt). The characterization of phytoplasma using iphy classifier reveled Ca. P. australasia belonging to 16SrIID subgroup was present along with CMV infection. In addition, the Solanum torvum grown in and around brinjal ecosystem showed severe mosaic and exhibited 99% nucleotide identity with CMV TNB isolate and these plants also act as inoculum source during the on and off cropping season in India. To our knowledge this is the first record of mixed infection of CMV and Ca. P. australasia in brinjal and first record of CMV infection in S. torvum in India.

Co-existence of chlorosis inducing strain of Cucumber mosaic virus with tospoviruses on hot pepper (Capsicum annuum) in India.

Cucumo- and tospoviruses are the most destructive viruses infecting hot pepper (chilli). A diagnostic survey was conducted to assess the prevalence of cucumo and tospoviruses in chilli growing tracts of Tamil Nadu. Infected plants showing mosaic with chlorotic and necrotic rings, veinal necrosis, mosaic mottling, leaf filiformity and malformation were collected. Molecular indexing carried out through reverse transcription polymerase chain reaction (RT-PCR) with coat protein gene specific primer of Cucumber mosaic virus (CMV) and tospovirus degenerate primer corresponding to the L segment (RdRp). Ostensibly, amplifications were observed for both CMV and tospoviruses as sole as well for mixed infections. The sequence analysis indicated that the Capsicum chlorosis virus (CaCV) and Groundnut bud necrosis virus (GBNV) to be involved with CMV in causing combined infections. The co-infection of CMV with CaCV was detected in 10.41% of the symptomatic plant samples and combined infection of CMV with GBNV was recorded in around 6.25% of the symptomatic plants surveyed. The amino acid substitution of Ser129 over conserved Pro129 in coat protein of CMV implies that CMV strain involved in mixed infection as chlorosis inducing strain. Further, the electron microscopy of symptomatic plant samples explicated the presence of isometric particles of CMV and quasi spherical particles of tospoviruses. This is the first molecular evidence for the natural co-existence of chlorosis inducing CMV strain with CaCV and GBNV on hot pepper in India.

Metabolites of Trichoderma longibrachiatum EF5 inhibits soil borne pathogen, Macrophomina phaseolina by triggering amino sugar metabolism.

An endophytic fungal antagonist Trichoderma longibrachiatum EF5 exhibited biocontrol activity against a soil-borne fungal pathogen Macrophomina phaseolina. Under dual co-culture, T. longibrachiatum EF5 showed 58% inhibition against M. phaseolina. Crude soluble metabolites (SMs) extracted from EF5 exhibited biocontrol activity (61%), which is more significant than the cell-free extract. Dual culture of both T. longibrachiatum EF5 and M. phaseolina displayed entangled mycelial structures and retarded hyphal growth. The metabolites responsible for antibiosis and pathogenic activity profiled through GC-MS revealed a total of 131 SMs from axenic culture and upon the interaction of T. longibrachiatum EF5 and M. phaseolina. Interestingly, potential plant-growth-promoting and antimicrobial compounds such as 1- pentanol, 1-hexanol, myristonyl pantothenate, bisabolol, d-Alanine, and diethyl trisulphide were unique with T. longibrachiatum EF5. Few compounds that were not observed or produced minimally under axenic culture were increased during their interaction (e.g., 1,6-anhydro-á-d-Glucopyranose and 5-heptyl dihydro-2(3H)-Furanone), suggesting antimicrobial action against the pathogen. This study also unraveled the induction of amino sugar metabolism when T. longibrachiatum EF5 interacts with M. phaseolina, which is responsible for colonization and counterfeiting the pathogen. Hence T. longibrachiatum EF5 could be a potential biocontrol agent employed for defense priming and plant growth promotion.

Is 177Lu-PSMA an effective treatment modality for mCRPC patients with bone and visceral metastasis?

OBJECTIVE: We analyzed the clinical outcome of lutetium-177 prostate-specific membrane antigen (177Lu-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with visceral metastasis. SUBJECTS AND METHODS: Ten patients of mCRPC with visceral metastasis were enrolled for one cycle of 177Lu-PSMA therapy. Number of efficacy and safety parameters, e.g., prostate-specific antigen (PSA), visual analog scale (VAS) and analgesic quantification scale (AQS), hemoglobin (Hb), total leukocytes counts (TLC), platelets, creatinine, & total bilirubin, were assessed and compared with Wilcoxon signed-rank test. The progression-free survival (PFS) curve was computed by the Kaplan-Meier method. The receiver operating characteristic curve (ROC) was also plotted for 177Lu-PSMA dose. P≤0.05 was considered significant. RESULTS: Liver (80%), lung (30%), adrenal (10%), and peritoneum (10%) were the sites of visceral metastasis in our study. On PSA response assessment, 10%, 60%, and 30% of the patients had partial response, stable disease, and progressive disease, respectively. Forty percent of the patients had improvement in the VAS, while 50% had improvement in the AQS score. Median PFS was 24 weeks in our study. A cut-off of 4.88GBq of 177Lu-PSMA was the best-predicted progression with 66.67% sensitivity and 100% specificity on ROC analysis. Thirty percent of the patients showed grade 3 anemia. No other significant toxicity was seen. CONCLUSION: Lutetium-177-PSMA was a reasonable palliative treatment option with limited toxicity for these end-stage mCRPC patients with visceral metastasis with adequate PSA stabilization. A synergistic drug amalgamation may be an ideal way to boost the outcome in the future.

Characterization of cucumber mosaic virus (CMV) subgroup IB infecting chilli in Tamil Nadu, India.

CMV (cucumber mosaic virus) is the most primitive virus infecting chilli (Capsicum annuum. L). The mosaic incidence with leaf filiformity, mosaic mottling and stunted growth was observed in major chilli growing regions of Tamil Nadu. CMV sap was inoculated on chilli, cowpea, bitter gourd, bottle gourd, ridge gourd, banana, cucumber, Nicotiana and Chenopodium plants. Host range studies revealed that CMV produced localized infection on Nicotiana and systemic symptoms on most of the test plants. The occurrence of CMV was confirmed through DAC-ELISA and RT-PCR analysis. Host plant samples tested with DAC-ELISA showed strong reaction with 1.7 optical density. For molecular characterization, total RNA isolated from infected plants used in RT-PCR with CMV specific primers. The specific amplicons were cloned and sequenced. The complete genome sequencing depicts CMV-RNA1 consist of 3339 nucleotides (nt), RNA2 and RNA3 with 3052nt and 2027nt respectively. Phylogenetic and nucleotide sequence analysis showed TN CMV isolates closely associated with subgroup IB rather than subgroup IA and II. Comparative sequence analysis indicates replicase protein to be more variable among five genes. CP sequence analysis showed 97-98 per cent identity with subgroup IB strains, 92-93 per cent identity with subgroup IA strains and 81-82 per cent identity with subgroup II strains. CMV-RNA3 was predicted to have recombination with Indian black pepper isolate (KU947031) between 165-505nt and Egyptian tomato isolate (KX014666) between 165-506nt positions.

Correction to: Safety Profile and Therapeutic Efficacy of One Cycle of Lu177-PSMA in End-Stage Metastatic Castration-Resistant Prostate Cancer Patients with Low Performance Status.

[This corrects the article DOI: 10.1007/s13139-019-00624-8.].

A Walk with Lu-177 PSMA: How Close we Have Reached from Bench to Bedside?

Metastatic castration-resistant prostate cancer (mCRPC) is a natural sequela in advanced prostate cancer following resistance to standard treatment regimes, where patients develop with rising PSA, bone pains, and high disease volume. Further palliative treatment is the need of the hour for ensuring disease control and quality of life. In recent times, many novel methods have been evolved for these patients. Endo-radioligand therapy with Lutetium 177 prostate-specific membrane antigen 617 (Lu-177 PSMA) based on the Theranostic concept has emerged as a promising tool among these. We present here the current status of Lu177-PSMA for mCRPC patient and future directions.

Effect of cardiac resynchronization therapy on septal perfusion and septal thickening: Association with left ventricular function, reverse remodelling and dyssynchrony.

BACKGROUND: We evaluated the effect of cardiac resynchronization therapy (CRT) on septal perfusion and thickening at 6 months post implantation assessed on Tc99m-MIBI Gated myocardial perfusion SPECT (GMPS).We also studied the association of change in septal perfusion and thickening with primary outcome defined as at least one [improvement in ≥1NYHA class, left ventricular ejection fraction (LVEF) by ≥ 5%, reduction of end-systolic volume (ESV) by ≥ 15%, and improvement ≥ 5 points in Minnesota living with heart failure questionnaire (MLHFQ)]. METHOD: One hundred and five patients underwent clinical and GMPS evaluation before and at 6 months post CRT. RESULT: Post CRT there was significant improvement in mean normalized septal perfusion uptake and in septal thickening (P value = 0.001, both). There was no significant relation between improvement in septal perfusion and primary outcome. However, improvement in septal thickening was statistically significant with favorable primary outcome (P = 0.001).There was no significant correlation between improvement of septal perfusion and improvement in LVEF, reduction in End diastolic volume (EDV), ESV, and Left ventricular Dyssynchrony (LVD). But, there was significant correlation between improvement of septal thickening and these parameters. CONCLUSION: Improvement in septal thickening was associated with reverse remodeling, improvement in LVEF, and reduction of LVD.

Safety Profile and Therapeutic Efficacy of One Cycle of Lu177-PSMA in End-Stage Metastatic Castration-Resistant Prostate Cancer Patients with Low Performance Status.

PURPOSE: The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status. METHODS: Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis. RESULTS: Partial response (PR), stable disease (SD) and progressive disease (PD) for PSA were seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88 GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables. CONCLUSION: We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.

Dysbiosis Disrupts Gut Immune Homeostasis and Promotes Gastric Diseases.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and also promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in the host, which in turn influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics, chemotherapeutic drugs, and any change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromilieu. Ligands released from dying microbes induce Toll-like receptor (TLR) mimicry, skew hypoxia, and cause sterile inflammation, which further contributes to the severity of inflammatory, autoimmune, and tumorous diseases. The major aim and scope of this review is both to discuss various modalities/interventions across the globe and to utilize microbiota-based therapeutic approaches for mitigating the disease burden.