Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

The intestinal tract is the largest digestive organ in the human body. It is colonized by, and consistently exposed to, a myriad of microorganisms, including bifidobacteria, lactobacillus, Escherichia coli, enterococcus, clostridium perfringens, and pseudomonas. To protect the body from potential pathogens, the intestinal tract has evolved regional immune characteristics. These characteristics are defined by its unique structure, function, and microenvironment, which differ drastically from those of the common central and peripheral immune organs. The intestinal microenvironment created by the intestinal flora and its products significantly affects the immune function of the region. In turn, specific diseases regulate and influence the composition of the intestinal flora. A constant interplay occurs between the intestinal flora and immune system. Further, the intestinal microenvironment can be reconstructed by probiotic use or microbiota transplantation, functioning to recalibrate the immune homeostasis, while also contributing to the treatment or amelioration of diseases. In this review, we summarize the relationship between the intestinal flora and the occurrence and development of diseases as an in-turn effect on intestinal immunity. We also discuss improved immune function as it relates to non-specific and specific immunity. Further, we discuss the proliferation, differentiation and secretion of immune cells, within the intestinal region following remodeling of the microenvironment as a means to ameliorate and treat diseases. Finally, we suggest strategies for improved utilization of intestinal flora.

Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.

Advances in pathogenesis and therapeutic strategies for osteoporosis.

Caesarean section (CS) results in the occurrence of the phenomenon 'niche'. A 'niche' describes the presence of a hypoechoic area within the myometrium of the lower uterine segment, reflecting a discontinuation of the myometrium at the site of a previous CS. Using gel or saline instillation sonohysterography, a niche is identified in the scar in more than half of the women who had had a CS, most with the uterus closed in one single layer, without closure of the peritoneum. An incompletely healed scar is a long-term complication of the CS and is associated with more gynaecological symptoms than is commonly acknowledged. Approximately 30% of women with a niche report spotting at 6-12 months after their CS. Other reported symptoms in women with a niche are dysmenorrhoea, chronic pelvic pain and dyspareunia. Given the association between a niche and gynaecological symptoms, obstetric complications and potentially with subfertility, it is important to elucidate the aetiology of niche development after CS in order to develop preventive strategies. Based on current published data and our observations during sonographic, hysteroscopic and laparoscopic evaluations of niches we postulate some hypotheses on niche development. Possible factors that could play a role in niche development include a very low incision through cervical tissue, inadequate suturing technique during closure of the uterine scar, surgical interventions that increase adhesion formation or patient-related factors that impair wound healing or increase inflammation or adhesion formation.

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Why do niches develop in caesarean uterine scars? Hypotheses on the aetiology of niche development

Background Endometriosis is a chronic, burdensome condition that is historically understudied. Consequently, there is a lack of understanding of the etiology of the disease and its associated symptoms, including infertility and chronic pelvic pain (CPP). Endometriosis development is influenced by estrogen metabolism and inflammation, which are modulated by several factors including the microbiome and the estrobolome (the collection of genes encoding estrogen-metabolizing enzymes in the gut microbiome). Therefore, there is increasing interest in understanding the role of microbiota in endometriosis etiology. Objective and rationale To date, there is no cure for endometriosis and treatment options often are ineffective. This manuscript will review the potential relationship between the microbiome and endometriosis, infertility and CPP and highlight the available data on the microbiome in relation to endometriosis and its related symptoms. The overarching goal of this manuscript is to inform future microbiome research that will lead to a deeper understanding of the etiology of the disease and possible diagnostic modalities and treatments. The potential impact of the microbiome on estrogen regulation modulated by the estrobolome, as well as inflammation and other endometriosis-promoting mechanisms within the genital tract, will be reviewed. The methodological limitations of microbiome-related studies will be critically assessed to provide improved guidelines for future microbiome and clinical studies. Search methods PubMed databases were searched using the following keywords: endometriosis AND microbiome, infertility AND microbiome, pelvic pain AND microbiome, IVF (in-vitro fertilization) AND microbiome, endometriosis AND infertility. Clinical and preclinical animal trials that were eligible for review, and related to microbiome and endometriosis, infertility or CPP were included. All available manuscripts were published in 2002-2021. Outcomes In total, 28 clinical and 6 animal studies were included in the review. In both human and animal studies, bacteria were enriched in endometriosis groups, although there was no clear consensus on specific microbiota compositions that were associated with endometriosis, and no studies included infertility or CPP with endometriosis. However, bacterial vaginosis-associated bacteria and Lactobacillus depletion in the cervicovaginal microbiome were associated with endometriosis and infertility in the majority (23/28) of studies. Interpretation of endometrial studies is limited owing to a variety of methodological factors, discussed in this review. In addition, metadata outlining antibiotic usage, age, race/ethnicity, menopausal status and timing of sample collection in relation to diagnosis of endometriosis was not consistently reported. Animal studies (6/6) support a bidirectional relationship between the gut microbiota and endometriosis onset and progression. Wider implications There is evidence that a dysbiotic gut or genital microbiota is associated with multiple gynecologic conditions, with mounting data supporting an association between the microbiome and endometriosis and infertility. These microbiomes likely play a role in the gut-brain axis, which further supports a putative association with the spectrum of symptoms associated with endometriosis, including infertility and CPP. Collectively, this review highlights the demand for more rigorous and transparent methodology and controls, consistency across the field, and inclusion of key demographic and clinical characteristics of disease and comparison participants. Rigorous study designs will allow for a better understanding of the potential role of the microbiome in endometriosis etiology and the relationship to other disorders of the female reproductive tract.

The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain

AIM To compare smooth muscle cells, type I collagen, and apoptosis of the lower uterine segment of women who had/without a prior cesarean delivery METHODS Alpha smooth muscle actin (α-SMA), type I collagen, and nuclear apoptosis were compared between the groups from lower uterine segment Twenty-eight controls and 82 with one prior cesarean delivery were included The women with a prior cesarean section were classified by time since the surgery: ≤3 years, >3 and ≤5 years, >5 and ≤7 years, >7 and ≤9 years, and >9 years RESULTS Smooth muscle volume density (VD) % was significantly lower in women who had cesarean sections in first three groups than in the controls (all, P<001) Type I collagen VD% was similar among all groups and the controls The number of apoptotic nuclei in the lower uterine segment of the scarred group was greater up to 3 years after surgery and less than in the control at 7-9 years The number of non-apoptotic nuclei in the scarred group was greater than controls up to 7 years after surgery CONCLUSION The lower uterine segment scar becomes stable at 3 years after cesarean delivery, and by 9 years, the scar is mature

A preliminary study of uterine scar tissue following cesarean section.

The consumption of probiotics and fermented foods has been very popular in recent decades. The primary aim of our study was to evaluate the effect of probiotics on the gut microbiota and the changes in inflammatory cytokines after an average of 6.7 weeks of probiotic administration among normal pregnant women. Thirty-two healthy pregnant women at 32 weeks of gestation were recruited and divided into two groups. The probiotic group ingested combined probiotics until after birth. The base characteristics of the probiotics and control groups showed no significant differences. The structure of the fecal microbiota at the genus level varied during the third trimester, and administration of probiotics had no influence on the composition of the fecal microbiota however, many highly abundant taxa and core microbiota at the genus level changed in the probiotic group when compared to the control group. The analysis of cytokines showed that IL-5, IL-6, TNF-α, and GM-CSF had equal levels between the baseline and control groups but were significantly increased after probiotic administration (baseline = control < probiotics). Additionally, levels of IL-1β, IL-2, IL-12, and IFN-γ significantly increased among the three groups (baseline < control < probiotics). This result demonstrated that probiotics helped to shift the anti-inflammatory state to a pro-inflammatory state. The correlation analysis outcome suggested that the relationship between the microbiota and the cytokines was not strain-dependent. The gut microbiota varied during the third trimester. The probiotics demonstrated immunomodulation effects that helped to switch over to a pro-inflammatory immune state in the third trimester, which was important for labor.

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Probiotic Supplementation During Human Pregnancy Affects the Gut Microbiota and Immune Status.

The present study was conducted to evaluate new methods to repair the reproductive function of the oviduct, thereby allowing gametes to combine and grow in vivo under natural circumstances. Sixty pathogen-free female New Zealand rabbits were divided into three groups: a wild-type group, an untreated control group, and a treatment group. Disposable sterile newborn sputum suction tubes were inserted into the urogenital tract to instill an Escherichia coli suspension into the uterine cavity to establish the chronic salpingitis model. Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) or normal saline were used to treat this infection via different methods. The therapeutic effect was assessed by evaluating morphology, inflammatory factors, proteinology, and pregnancy outcomes. Oviducts of New Zealand rabbits in the untreated control group showed structural failure and abnormal supermicrostructure of epithelial cells. WJMSCs could partially repair the structure and supermicrostructure of the tubal epithelium. The concentration of tumor necrosis factor (TNF)-α in the untreated control group was significantly higher than that in the wild-type group (P = 0.015). The concentration of TNF-α in the local treatment group was significantly lower than that in the untreated control group (P = 0.011). The expression of oviductal glycoprotein (OVGP) and OVGP mRNA in the wild-type group was significantly higher than those in the untreated control group (P = 0.024 and P = 0.013, respectively). The litter size of the treatment group was 2 ± 2.39 kits, which was higher than that of the untreated control group (P = 0.035). Chronic inflammation can destroy the structure of the oviduct and the supermicrostructure of epithelial cells as well as leading to infertility. WJMSC transplantation therapy in rabbits with chronic salpingitis partially restored fertility. WJMSCs also repaired the structure of the tubal epithelium subjected to chronic inflammation, decreased the level of inflammatory factors, and partially restored the secretion level of OVGP.

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Treatment evaluation of Wharton’s jelly-derived mesenchymal stem cells using a chronic salpingitis model: an animal experiment

To study the effect of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) on the rat salpingitis model, 50 female Wistar rats were randomly divided into one control and five model groups. Mixed bacteria were injected into the oviducts of model groups. The treated acute and chronic groups received intraperitoneal injections of WJMSCs (1 x 10(6)) once a week for three weeks. Serum inflammation factor, collagen fiber content and oviduct-specific glycoprotein (OVGP) levels were detected in control, chronic, ex-treatment acute and chronic, and treated acute and chronic groups (N = 5 for each group). Pregnancy rate and litter size of control, chronic, treated acute and treated chronic groups were compared. Serum TNF-α and INF-γ levels increased in ex-treatment acute and chronic groups, and restored to normal in the acute treated group but not in the treated chronic group. Oviduct collagen fibers did not increase significantly before or after treatment in the acute group, but it increased in the ex-treatment chronic group and did not improve after treatment. After treatment, OVGP levels restored to normal in the acute group but reduced in the ex-treatment and treated chronic groups and chronic group. The pregnancy rate and litter size of the treated acute group recovered to normal, but in the treated chronic group and chronic model group, they decreased significantly. Thus, intraperitoneal injection of WJMSCs could recover the function of the oviduct in acute salpingitis rats, but its effect on chronic salpingitis was poor. Timely treatment of salpingitis is crucial to preserve reproductive function.

https://www.funpecrp.com.br/gmr/year2015/vol14-2/pdf/gmr5336.pdf

Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis.

Probiotic supplementation has been shown to be beneficial and is now widely promoted as an auxiliary medicine for maternal health, but the underlying mechanism is still unclear. Thus, this study aimed to explore the effects of probiotic supplementation on the placental autophagy-related proteins LC3 and Beclin1. A population-based cohort of specimens was collected under sterile conditions from 37 healthy nulliparous pregnant women who underwent systemic examination and delivered at the First Affiliated Hospital of Jinan University (Guangzhou, China). At 32 weeks of gestation, the pregnant women in the probiotic group were orally supplemented with golden bifid, and the pregnant women in the control group received no probiotic. Pregnant women with pregnancy-associated complications were excluded in the follow-up period, and 25 pregnant women undergoing spontaneous delivery were enrolled. The placental tissue specimens were collected at term. Western blotting was used to detect the protein expression, and qRT-PCR was used to detect the mRNA expression of the placental autophagy-related proteins LC3 and Beclin1. ①There was no significant difference in the expression levels of either LC3 or Beclin1 protein between the two groups (P > 0.05). ②Probiotic supplementation induced a modest but not significant decrease in the content of LC3-mRNA with a significant decrease in the content of Beclin1-mRNA (P < 0.05). Our study indicates that probiotic supplementation may reduce Beclin1-mRNA levels.

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Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy

Juan Zhou

Papers

A preliminary study of uterine scar tissue following cesarean section.

Probiotic Supplementation During Human Pregnancy Affects the Gut Microbiota and Immune Status.

Treatment evaluation of Wharton’s jelly-derived mesenchymal stem cells using a chronic salpingitis model: an animal experiment

Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis.

Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy