{"paper_id":"77737bda-9592-42e4-b5c9-2922c73b64c3","body_text":"Review Article\nVolume 7 Issue 3 - January 2020\nDOI: 10.19080/GJORM.2020.07.555713\nGlob J Reprod Med\nCopyright © All rights are reserved by M Bardi\nEndometriosis and Microbiota: Is there a \nRelationship with the Perinatal Period?\nM Bardi1*, F Arioli2 and N Rovelli3\n1Senior Consultant, Italy\n2Midwife, freelancer, Italy\n3Midwife Lecturer, University Milano Bicocca, Italy\nSubmission: December 17, 2019; Published: January 9, 2020\n*Corresponding author: M Bardi, Senior Consultant and Referent of the Multidisciplinary Team for Endometriosis care at the Policlinic San Pietro \n(San Donato Group) in Ponte San Pietro, Italy\nGlob J Reprod Med 7(3): GJORM.MS.ID.555713 (2020)  0057\nIntroduction\nEndometriosis is defined as the presence of endometrial \nglands and stroma outside the uterine cavity, predominantly, \nbut not exclusively, in the pelvic compartment. It is an oestrogen \n-dependent chronic inflammatory con¬dition that affects women \nin their reproductive period and is associated with pelvic pain and \ninfertility [1]. The prevalence of endometriotic disease seems to \nbe ~5%, with a peak between 25 years and 35 years of age [2]. \nThe disease seems frequent in adolescent women with chronic \npelvic pain [3]. The pathogenic hypothesis supported by the most \nrobust evidence is based on the so-called retrograde menstruation \nphenomenon. Viable endometrial fragments are driven through the \nfallopian tubes, possibly by a pressure gradient originating from \ndys-synergic uterine contractions. Once they reach the peritoneal \ncavity, they can implant, grow and invade onto pelvic structures. \nThe likelihood of this event is influenced epidemiologically by any \nmenstrual, reproductive or personal factor that would augment \npelvic contamina¬tion by regurgitated endometrium such as \nearly age at menarche or a long duration of menstrual flows, and \nbiologically by any alteration at the molecular level that favors \nthe stepwise process of cell implantation and growth at ectopic \nlocations [4].\nMicrobiota\nThe term microbiota indicates the set of microorganisms \nthat live and colonize a specific environment at a specific \ntime [5]. In particular, the human microbiota is an organism \ncomposed of bacteria, archaea and microbial eukaryotes, such \nas protozoa, fungus and nematodes. It is estimated that there are \napproximately 10,000 billion microorganisms belonging to the \nhuman microbiota against 1000 billion human cells. According to \nsome researchers, these microorganisms have such an influence \non human physiology that they should be considered part of its \ngenome [6]. The 10,000 billion microorganisms that live in and \non the body perform different functions: protective, structural \nand metabolic. To confirm this hypothesis, the intestinal and \nvaginal microbiome have been variously studied also with the \nnew molecular techniques. The latter mainly concerns the gene \nsequencing for the 16S subunit of ribosomal RNA, or rRNA, or \na specific gene of all bacteria. The metabolic capacities of the \nbacteria have been deciphered sequencing all the genes of a \nmicrobial community (Table 1). The studies object was mainly the \nvaginal microbiome and the influence of its alterations in health \nand gynecological pathology. As early as 2002, Dr. David Barker \nintroduced the concept of “fetal origins of adult disease” , arguing \nAbstract\nThe gut microbiota is a complex community of bacteria residing in the intestine. Animal models have demonstrated that several factors \ncontribute to and can significantly alter the composition of the gut microbiota, including genetics; the mode of delivery at birth; the method \nof infant feeding; the use of medications, especially antibiotics; and the diet. The intestinal microflora provides a strong defense against \nintestinal pathogens and may be altered in inflammatory conditions that impact the gut, such as endometriosis. This research is in the form of a \nquantitative study aimed at discovering the relationship with development of the intestinal microbiome in the perinatal period and the impact \nof these microbiota on the local endometrial microenvironment as these mechanisms may influence gynecologic health outcomes and onset of \nendometriosis. We hypothesized that disease-specific changes of gut microbiota in patients with endometriosis may a provide new insights for \npsychological intervention, to improving the prognosis of endometriosis patients. \nKeywords: Gut microbiota; Endometriosis; Pregnancy; Neonatal period\n\n\nHow to cite this article: M Bardi, F Arioli, N Rovelli. Endometriosis and Microbiota: Is there a Relationship with the Perinatal Period?. Glob J Reprod Med. \n2020; 7(2): 5556713. DOI: 10.19080/GJORM.2020.07.55567130058\nGlobal Journal of Reproductive Medicine\nthat the intrauterine environment in which the fetus develops \ncan influence postnatal conditions. The microbiome is therefore a \nmechanistic mediator in the origins of the development of health \nand disease [7].\nTable 1: Demographic and general information of the study respondents.\nGeneral Information’s\nIndicate your age:\nIndicate your nationality:\nIndicate your body weight (kg):\nIndicate your height (m):\nIndicate the predominant type of food:\nHow many pregnancies did you have (including pregnancies that were interrupted in the first few months)?\nHow many children did you have?\nHow old did you find yourself suffering from endometriosis?\nHow many years have you been suffering from it?\nMicrobiota and Maternal-Fetal Relationships \nUntil recently, the intrauterine environment was considered \nsterile, as were the fallopian tubes and the anatomical appendages \nof pregnancy (placenta and amniotic fluid). The theory that the \nfirst colonization of the gastrointestinal tract of the new-born \noccurs at the time of the first breastfeed is also widespread in \nthe literature. However, several studies of the human microbiome \nover the last few years, through the molecular-based technique of \nrRNA 165 gene sequencing, indicate that this fetal colonization \nbegins already in utero [8]. Non-pathogenic bacteria have also \nbeen found in amniotic fluid and placentas of healthy new-\nborns, suggesting an exchange of microbes between mother and \nfetus [9]. Recently RW Walker [10] sampled 15 mother-child \ntwosomes: meconium contained bacteria detected in the placenta \nand amniotic fluid, despite the unique composition and function of \nmeconium and found that bacterial transmission increased during \npregnancy. These results indicate that the maternal microbiome \ncarry out a fundamental role in shaping the fetal intestinal \nmicrobiome, taking part in a vertical transfer.  Recent studies \nhave characterized how host genetics, prenatal environment \nand delivery mode can shape the new-born microbiome at birth. \nFollowing this, post-natal factors, such as antibiotic treatment, \ndieting, and exposure to a variety of microbial organisms during \nearly life has been hypothesized to a protective effect in the new-\nborn. Furthermore, epidemiological studies have shown that \nthere are other diseases in infants during childhood increase \nthe risk for several diseases, highlighting the importance of \nunderstanding early life microbiome composition [11].  Maternal \nvaginal infections or periodontitis can result in bacteria invading \nthe uterine environment (Table 2-4). Gut and oral microbiota \ncould be transported through the bloodstream from the mother \nto the fetus. Delivery mode shapes the initial bacterial inoculum \nof the new-born. Postnatal factors such as antibiotic use, diet \n(such as breast-feeding versus formula, and introduction of solid \nfood), genetics of the infant and environmental exposure further \nconfigure the microbiome during early life [11].\nTable 2: History of birth of the study respondents.\nHistory of Your Birth\n(In this section you will be asked for information about your\nmother’s pregnancy and how you were born and fed, about your health at birth and in your first year of life. If you do not have this information, we \ninvite you, if possible, to ask your parents).\nWhich month of pregnancy you were born in?\nWith which birthing methods you were born?\nHow long have you been breast-fed?\nLess than a week of life\nHow many months of life did wean take, or did you start eating\nfoods other than breast milk or artificial milk?\nDuring your first year of life, did you have to take antibiotics due to health problems? If yes, how many months of life?\n\nHow to cite this article: M Bardi, F Arioli, N Rovelli. Endometriosis and Microbiota: Is there a Relationship with the Perinatal Period?. Glob J Reprod Med. \n2020; 7(2): 5556713. DOI: 10.19080/GJORM.2020.07.55567130059\nGlobal Journal of Reproductive Medicine\nTable 3: We have been investigated diseases suffered in early childhood.\nThe First 6 Years of Life\n(If you do not have this information, we ask you to ask your parents if possible)\nDuring the first six years of life, have you ever suffered from one or more of the following diseases? If the answer is yes, indicate which one (s)\nTable 4: Symptoms associated with gut dysbiosis and endometriosis after six years of life.\nAfter the Six Years of life\nHave you suffered one or more of the following diseases / disorders during your life?\nCeliac disease\nIneffective digestion\nAbdominal swelling\nConstipation and / or diarrhea\nUrinary tract infections\nPelvic pain\nMenstrual pain\nPain following sexual intercourse\nHeadache\nChronic fatigue\nInsomnia\nRecurrent viral infections, flu\nDermatitis and allergies\nI have never suffered from any disease / disorder\nOther:\nMicrobiota, Dysbiosis and Inflammation\nTable 5: History of their birth.\n Not Affected by Endometriosis Affected by Endometriosis\nGestational era\n- At term: 90.9% - At term: 86.5%\n- After 7th month and before\n- After 7th month and before\n- Before the 7th month: 0.5%\nBirthing methods - Vaginal birth: 84.1% - Vaginal birth: 84.4%\n - Cesarean section: 15.9% - Cesarean section: 15.6%\nBreastfeeding\n- Less than 1 week: 5.7% - Less than 1 week: 5.8%\n- Less than 1 month: 14.8% - Less than 1 month: 13.3%\n- Up to 3 months: 21.6% - Up to 3 months: 23.4%\n- Up to 6 months: 15.9% - Up to 6 months: 22.7%\n- Up to 1 year: 17% - Up to 1 year: 12.4%\n- For more than 1 year: 10.2% - For more than 1 year: 6%\n- Never breastfed: 14.8% - Never breastfed: 16.3%\n\nHow to cite this article: M Bardi, F Arioli, N Rovelli. Endometriosis and Microbiota: Is there a Relationship with the Perinatal Period?. Glob J Reprod Med. \n2020; 7(2): 5556713. DOI: 10.19080/GJORM.2020.07.55567130060\nGlobal Journal of Reproductive Medicine\nWeaning\n- 3 months: 10.3% - 3 months: 11.1%\n- 4 months: 24.1% - 4 months: 16.7%\n- 5 months: 23% - 5 months: 19.1%\n- At 6 months: 27.6% - At 6 months: 36%\n- 7 months: 8% - 7 months: 7.8%\n- After 8 months: 6.9% - After 8 months: 9.3%\nAntibiotics in the first year of \nlife\nUsed by 46% of women. Used by 50% of women.\n- At birth: 2.4% - At birth: 5.9%\n- In the first 6 months: 29.3% - In the first month: 4.4%\n- Between 6 months and 1 year 68.3%\n- In the first 6 months: 17.7%\n- Between 6 months and 1 year 71.9%\nTable 6: In the first 6 years they have suffered from.\nNot Affected by Endometriosis Affected by Endometriosis\nCommon infectious diseases childhood 70.10% 69%\nAsthma 3.40% 8.40%\nAllergies 9.20% 10.90%\nFood intolerances 4.60% 6.30%\nInfections that require the use of antibiotics 37.90% 32.90%\nNo disease 16.10% 14.20%\nOther 3.40% 7.70%\nDysbiosis is an alteration of the balance and composition of the \nmicrobiota and microbiome that colonizes a specific anatomical \nsite. Intestinal dysbiosis, for example, involves a set of signs, \nsymptoms and disorders of the gastrointestinal tract, which can \nalso have consequences on organs and systems distant from the \nintestine [12]. An important consequence of the alteration of the \nmicrobial community is the modification of the functional gene \npart present in the intestinal microbiome. Dysbiosis negatively \ninfluences homeostasis through reduced microbial diversity \nand increased inflammatory reaction. A reduction in cell-cell \njunctions occurs at the level of the intestinal epithelium, which \nleads to an increase in permeability and subsequently to bacterial \ntranslocation. The latter can lead to an inflammatory state with the \nconsequent exacerbation or induction of the disease [13]. Among \nthese numerous discoveries, the various studies on the influence \nof human (especially intestinal) microbiome on oestrogen \n-dependent diseases play a fundamental role. It is well known, \nfor example, that the high levels of adipose tissue are associated \nwith increased production of oestrogen, which is considered \na key factor in female reproductive tumours and therefore in \nhyperplasia. Many tissues express oestrogen receptors, including \nintestines, brain, bones and adipose tissue (Table 5 & 6). Oestrogen \nplays a significant role in numerous gynaecological conditions \nwith different mechanisms, such as increasing the epithelial \nbarrier, glycogen levels, mucus secretion and indirectly decreasing \nvaginal pH by promoting the abundance of Lactobacilli and acid \nproduction lactic acid [13].\nOestroboloma\nAlong with the new knowledge on the microbiome, in recent \nyears scientific discoveries concerning oestroboloma are also \nspreading. This term means “a complex interaction between \noestrogen, intestinal microbiome and sites of the distal mucosa”; \nit is defined as “gene repertoire of the gut microbiota that is able \nto metabolize oestrogen “ [13]. In fact, not only the oestrogens \ncan modify the intestinal microbiome, but the latter can also \nsignificantly influence the levels of oestrogen: they are metabolized \nby the enzyme beta-glucuronidase, secreted by the microbes, in the \npassage from their forms conjugated to their forms deconjugate; \nthe oestrogens are thus made free and available to bind to their \nreceptors, influencing the physiological oestrogen -dependent \nprocesses. Oestroboloma can regulate homeostasis at sites of \nintestinal and distal mucosa (Table 7). When dysbiosis occurs, the \naction of beta-glucuronidase is altered, causing hyperactivation \nand / or a deficiency of the estrogenic value and thus contributing \nto oestrogen -related pathological states [13].\n\nHow to cite this article: M Bardi, F Arioli, N Rovelli. Endometriosis and Microbiota: Is there a Relationship with the Perinatal Period?. Glob J Reprod Med. \n2020; 7(2): 5556713. DOI: 10.19080/GJORM.2020.07.55567130061\nGlobal Journal of Reproductive Medicine\nTable 7: After 6 years of life they have suffered from.\nNot Effected by Endometriosis Affected by Endometriosis\nCeliac Disease 3.40% 4%\nIneffective digestion 17.20% 29.60%\nAbdominal swelling 28.70% 67.20%\nConstipation and/or diarrhea 39.10% 68.50%\nUrinary tract infections 34.50% 45.10%\nPelvic pain 8% 65.30%\nMenstrual pain 62.10% 88.70%\nDyspareunia 8% 58.70%\nHeadache 35.60% 54.70%\nChronic fatigue 14.90% 64.10%\nInsomnia 6.90% 31.80%\nRecurrent viral infections 11.50% 25%\nDermatitis and allergies 33.30% 37.30%\nNo disease 6.90% 1.90%\nOther 1.10% 5.20%\nMicrobiota and Endometriosis\nRecent studies present strong evidence for an association \nbetween dysbiosis, i.e. disruption of the gut microbiota, and \ninflammatory bowel disease, neuropsychiatric diseases, psoriasis, \narthritis, and some cancers, especially colon cancer [12]. This \nis explained by the potential immunoregulatory function of \nthe gut microbiota playing a role in systemic inflammatory \ncellular responses. Since abnormal inflammatory response \nand activation of immune cells in the peritoneal cavity are \nthought to play a role in the pathogenesis of endometriosis, an \nassociation between microbiota and endometriosis is likely [14]. \nTherefore, the current mechanistic studies on endometriosis \nare insufficient. Patients with endometriosis are at high risk of \nvarious chronic diseases, such as autoimmune diseases, cancer, \nasthma / atopic diseases, cardiovascular and inflammatory bowel \ndiseases [15]. Endometriosis shares similar characteristics, \nsuch as decreased apoptosis, elevated cytokine levels and cell-\nmediated abnormalities, with several autoimmune diseases, \nthus endometriosis holds a strong relationship with complex \nimmune disorders [16]. Prior research has shown that dysbiosis \nleads to increased oestrogen levels in the circulation [17]. \nIncreased oestrogen exposure can stimulate growth of ectopic \nendometriotic foci and inflammatory activity in them. Even the \nintestinal microbiota has been shown to be an important regulator \nof these inflammatory processes: macrophages, neutrophils and \nmast cells can be influenced by intestinal microbial variations \nand by its greater epithelial permeability [14]. Furthermore, the \nactivation of IL-17-secreting CD4 T lymphocytes derives from this \ninflammatory reaction, a proinflammatory cytokine that appears \nto play a fundamental role in the pathogenesis of endometriosis by \nhypervascularization of the peritoneal surface, with consequent \nimplantation and proliferation of endometrial tissue ectopic. The \nconcentration of IL-17 was significantly superior in the peritoneal \nfluid of women with endometriosis. Furthermore, the composition \nof the intestinal microbiota is correlated with the homeostasis of \nstem cells and progenitor in the bone marrow and an involvement \nof these cells in the development of endometriosis has been \ndemonstrated [14]. It is plausible that microbiota can play a \nrole in the development of endometriosis by affecting the host’s \nepigenetic, immunologic and / or biochemical functions [18].\nMaterials and Method\nVoluntary completion of an anonymous survey was promoted \n(online and paper sampling). The survey was designed on \nthe basis of information from literature review on multiple \ninteractions between endometriosis and microbiota, and on the \nhypothesis that an alteration of the fetal and neonatal microbiota \ncould, in some way, interfere with the onset of endometriosis. We \nsent a questionnaire to 100 women suffering from endometriosis \nand 100 healthy women (which we call “controls”). The 200 \nwomen were asked to report the course of the 3rd trimester of the \npregnancy from which they were born (naturally asking for news \nto their mother), the methods of birth and the first 6 months of \ntheir life. We then asked to report on any pathologies that arose in \nthe following years.\nConsent to the Treatment of Sensitive Data\nAfter having read and having understood the information \nabove, concerning the study: “Health and gynecological \npathology in relation to the human microbiome: development \nof new perspectives of Obstetric assistance for the promotion \n\nHow to cite this article: M Bardi, F Arioli, N Rovelli. Endometriosis and Microbiota: Is there a Relationship with the Perinatal Period?. Glob J Reprod Med. \n2020; 7(2): 5556713. DOI: 10.19080/GJORM.2020.07.55567130062\nGlobal Journal of Reproductive Medicine\nof women’s health” agrees does not consent to the processing of \npersonal and sensitive data collected in the context of this study, \naccess, consultation and any subsequent processing of the data \ncollected from the components research group bodies and other \nauthorized researchers. The processing of the data collected as \npart of the experimentation as well as their communication to \nother third parties and / or publication for scientific purposes are \npermitted but can only take place after the data has been made \nanonymous, under the responsibility and under the responsibility \ndirect experimenter. The data collected will also be processed \nin accordance with the privacy regulations (GDPR, General Data \nProtection Regulation - EU Regulation 2016/679) and will always \nbe represented in aggregate form. The results of the research \nwere found from the responses of 88 women not affected by \nendometriosis and 81 women who are affected. The criteria \nare represented by the fertility and the absence of the state of \npregnancy in all participating women.\na) To answer the questionnaire addressed to women \nnot affected by endometriosis, note the relevance of women \nbetween 20 and 24 years with a percentage of 28.4%, against \n17% of women over the age of 40. In 97.7% are women of \nItalian nationality. Body weight varies between 41 kg and 95 kg, \nwhile height varies between 1.50 m and 1.80 m, with a peak at \n1.60 / 1.65 m. 97.7% report an omnivorous diet. 46.6% had no \npregnancy in their lives, while 29.5% reported one, 9.1% of them \nreported three, 8% reported two, 6.8% reported more than three. \nFurthermore, 47.7% have no children, 29.5% have one, 17% have \ntwo, 5.7% have three. \nb) To answer the questionnaire addressed to women \nsuffering from endometriosis, note the relevance of women with \nover 40 years, with a percentage of 31.1%, followed by 30.2% of \nwomen between 35 and 39 years, 21.3% between 30 and 34 years \nup to 3.8% of women between 20-24 years. In 96.4% they are \nwomen of Italian nationality. Body weight varies between 40 kg \nand 130 kg, while the height varies between 1.50 m and 1.82 m. \n93.9% report a diet omnivorous. 60.6% had no pregnancy in their \nlives, while 19.3% reported one, 14.3% of them reported two. \nFurthermore, 67.6% have no children, 18.5% have one, 12% have \nhad children. These women found that they had endometriosis \nbetween 1 and 50 years. 45.3% are affected by more than 10 \nyears, 21% for more than 5 years, 2.8% for 5 years, 2.8% for 3 \nyears, 5.6% for 2 years.\nConclusion\nThe answers received show that there were no differences \nbetween the two groups as regards the course of the third \ntrimester of intra-uterine life, the methods of birth, breastfeeding \nand any therapies performed in the first 6 months of life. What \nis certain is that some modification of the microbiota has taken \nplace, since in the following years of life the women who then had \nendometriosis presented several pathologies in a much greater \npercentage than the controls. Pathologies, moreover, closely \nrelated to alterations of the intestinal microbiota. We believe that \nour survey is a starting point for further, more extensive and in-\ndepth research to correlate the alterations of the microbiota that \noccur at particularly early ages in a woman’s life and that can \nintervene in the genesis or predisposition to endometriosis.\nReferences\n1. Giudice LC Clinical practice (2010) Endometriosis. N Engl J Med 362: \n2389-2398.\n2. Parazzini F, Vercellini P , Pelucchi C (2012) In: Endometriosis science \nand practice. Giudice LC, Johannes LH, Healy DL, (Eds.), pp. 19-26. \n3. Janssen EB, Rijkers ACM, Hoppen brouwers K, Meuleman C, D Hooghe \nTM (2013) Prevalence of endometriosis   diagnosed by laparoscopy in \nadolescents with dysmenorrhea or chronic pelvic pain: a systematic \nreview. Hum Reprod Update 19(5): 570-582.\n4. Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of \nendometriosis. Fertil Steril 98(3): 511-519.\n5. Piccini F (2003) Alla scoperta del microbioma umano: Flora batterica, \nnutrizione e malattie del progresso. Fabio Piccini. Edizione del Kindle.\n6. Andreas Schwiertz (2016) Microbiota of the Human Body: Implications \nin Health and Disease. cap 4: 6-7. \n7. DJP Barker, JG Eriksson, T Forsén, C Osmond (2002) Fetal origins of \nadult disease: strength of effects and biological basis.  Int J Epidemiol \n31(6): 1235-1239.\n8. Mc Elroy K, Regan M, Chung S (2017) Health and the Human \nMicrobiome: A Primer for Nurses. Am J Nurs 117(7): 24-42.\n9. Stiemsma LT , Michels KB (2018) The Role of the Microbiome in the \nDevelopmental Origins of Health and Disease. Pediatrics 141(4): 243.\n10. Walker RW (2017) The prenatal gut microbiome: are we colonized \nwith bacteria in utero. Pediatric Obesity 12(1): 3-17.\n11. Tamburini S, Shen N, Wu HC JC (2016) The microbiome in early life: \nimplications for health outcomes. Nat Med 22(7): 713-722.\n12. Weiss GA, Hennet T (2017) Mechanisms and consequences of intestinal \ndysbiosis. Cell Mol Life Sci 74 (16): 2959-2977.\n13. Baker J, Al Nakkash L, Herbst Kralovetz M (2017) Review: Estrogen–\ngut microbiome axis: Physiological and clinical implications. Maturitas \n103: 45-53. \n14. Laschke MW, Menger MD (2016) The gut microbiota: a puppet master \nin the pathogenesis of endometriosis. Am J Obstet Gynecol 215(68): \ne61-68.\n15. Kvaskoff M, Mu F, Terry KL, Harris HR, Poole EM (2015) Endometriosis: \na high-risk population for major chronic diseases? Hum Reprod Update \n21(4): 500-516.\n16. Beste MT , Pfaffle Doyle N, Prentice EA, Morris SN, Lauffen burger \nDA, et al. (2014) acson KB, Griffith LG. Molecular network analysis \nof endometriosis reveals a role for c-Jun-regulated macrophage \nactivation. Sci Transl Med 6(222): 222ra216.\n17. Flores R (2012) Fecal microbial determinants of fecal and systemic \nestrogens and estrogen metabolites: a cross-sectional study. J Transl \nMed 10: 253.\n18. Ming Yuan, Dong Li, Zhe Zhang, Huihui Sun, Min An, et al. (2018) \nEndometriosis induces gut microbiota alterations in mice. Hum Reprod \n33(46): 607-616.\n\nHow to cite this article: M Bardi, F Arioli, N Rovelli. Endometriosis and Microbiota: Is there a Relationship with the Perinatal Period?. Glob J Reprod Med. \n2020; 7(2): 5556713. DOI: 10.19080/GJORM.2020.07.55567130063\nGlobal Journal of Reproductive Medicine\nYour next submission with Juniper Publishers    \n      will reach you the below assets\n• Quality Editorial service\n• Swift Peer Review\n• Reprints availability\n• E-prints Service\n• Manuscript Podcast for convenient understanding\n• Global attainment for your research\n• Manuscript accessibility in different formats \n         ( Pdf, E-pub, Full Text, Audio) \n• Unceasing customer service\n                        Track the below URL for one-step submission \n         https://juniperpublishers.com/online-submission.php\nThis work is licensed under Creative\nCommons Attribution 4.0 License\nDOI: 10.19080/GJORM.2020.07.5556713","source_license":"CC0","license_restricted":false}