There are a great number of beneficial commensal microorganisms constitutively colonizing the mucosal lining of the lungs. Alterations in the microbiota profile have been associated with several respiratory diseases such as pneumonia and allergies. Lung microbiota dysbiosis might play an important role in the pathogenic mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as elicit other opportunistic infections associated with coronavirus disease 2019 (COVID-19). With its increasing prevalence and morbidity, SARS-CoV-2 infection in pregnant mothers is inevitable. Recent evidence shows that angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) act as an entry receptor and viral spike priming protein, respectively, for SARS-CoV-2 infection. These receptor proteins are highly expressed in the maternal-fetal interface, including the placental trophoblast, suggesting the possibility of maternal–fetal transmission. In this review, we discuss the role of lung microbiota dysbiosis in respiratory diseases, with an emphasis on COVID-19 and the possible implications of SARS-CoV-2 infection on pregnancy outcome and neonatal health.

We hypothesized that alteration of the dietary arginine-methionine balance might inhibit tumor growth and suggest nutritional strategies for cancer therapy. The Morris hepatoma 3924A was subcutaneously transplanted in ACI rats. Control diets containing normal levels of arginine, methionine, and other amino acids in replacement of protein (24%), carbohydrates (59%), fat (10%), and fiber, vitamins, and minerals (7%) were fed for 28 days. Six experimental diets were adjusted to maintain amino acids at 23-25% and carbohydrates at 58-60%; these diets were 1%-2% deficient in arginine or supplemented with 1-2% arginine (expressed as percent amino acid content of diet) in combination with normal, deficient, and supplementary levels of methionine. Daily food intake was unaffected by the experimental diets. The control groups gained 26.4 +/- 2.8 g body weight, and small body weight decrements ranged from 3.5% to 8.4% in the groups fed the experimental diets. Tumor weight of controls was 8.5 +/- 1.5% of body weight. The experimental diets that produced significant tumor growth inhibition (TGI) were 1) the arginine-methionine-deficient diet, 2) the arginine-excess-methionine-deficient diet, 3) the arginine-deficient diet, and 4) the excess-arginine diet. Diets containing excess methionine failed to produce TGI. TGI resulted in tumor weights 41-46% of control values. TGI was associated with significantly lower blood urea nitrogen, plasma protein, and tumor spermidine-to-spermine ratio than in tumor-bearing controls. It is concluded that dietary alteration of a single amino acid, arginine, might be a potentially useful nutritional strategy for controlling tumor growth.

Previous studies have shown that alteration of the dietary arginine-methionine balance by use of synthetic L-amino acids inhibits tumor growth of a subcutaneously transplanted Morris hepatoma at the expense of maintaining body weight. However, L-methionine is susceptible to degradation and, therefore, may contribute to a deficiency state. The present studies were performed to determine whether growth of subcutaneous hepatoma transplants is inhibited, and body growth maintained, when rats are fed diets containing L-methionine in replacement of N-acetyl-L-methionine (NALM) for 28 days. Tumor-free and tumor-bearing rats fed a control diet, with amino acids replacing protein, had gains in body weight: 31.3 +/- 1.0 and 19.1 +/- 0.5 g (12% and 7%), respectively. Rats fed six experimental diets, with varying L-arginine-NALM balances, had body weight gains ranging from 18.4 +/- 0.3 to 26.7 +/- 0.9 g (7-10%). Tumor weight of control rats was 10.65 +/- 0.24% of body weight. Diets supplemented with L-arginine in combination with normal and deficient NALM decreased tumor weights by 35% and 38%, respectively, It is concluded that dietary replacement of L-methionine with NALM and supplementation with L-arginine inhibits growth of a subcutaneously transplanted Morris hepatoma in the absence of cachexia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a dreadful novel coronavirus with global health concerns among pregnant women. To date, the vertical transmission of SARS-CoV-2 during pregnancy remains controversial. We briefly report recent findings of placental response to SARS-CoV-2 infection and updates on vertical transmission. We systematically searched PubMed and Google Scholar databases according to PRISMA guidelines for studies reporting the effects of SARS-CoV-2 infection on the placenta and possibility of vertical transmission. We identified 45 studies reporting 1,280 human placentas that were analyzed by molecular pathology methods and 11,112 placenta-derived cells from a publicly available database that was analyzed using bioinformatics tools. The main finding of this study is that the SARS-CoV-2 canonical entry receptors (ACE2 and TMPRSS2) are abundantly expressed on the placenta during the first trimester, and this expression diminishes across gestational age. Out of 45 eligible studies identified, 24 (53.34%) showed no evidence of vertical transmission, 15 (33.33%) supported the hypothesis of very rare, low possibility of vertical transmission and 6 (13.33%) were indecisive and had no comment on vertical transmission. Furthermore, 433 placentas from 12 studies were also identified for placental pathology investigation. There was evidence of at least one form of maternal vascular malperfusion (MVM), 57/433 (13.1%), fetal vascular malperfusion (FVM), 81/433 (18.7%) and placental inflammation with excessive infiltration of CD3+ CD8+ lymphocytes, CD68+ macrophages and CD20+ lymphocytes in most of the eligible studies. Decidual vasculopathy (3.2%), infarction (3.2%), chronic histiocytic intervillositis (6.0%), thrombi vasculopathy (5.1%) were also observed in most of the MVM and FVM reported cases. The results indicated that SARS-CoV-2 induces placenta inflammation, and placenta susceptibility to SARS-CoV-2 decreases across the pregnancy window. Thus, SARS-CoV-2 infection in early pregnancy may adversely affect the developing fetus.

The endocannabinoid system (ECS) is associated with several physiological processes including reproduction. This system consists of the cannabinoid receptors, endocannabinoid ligands and enzymes which metabolize and degrade these fatty acids. Recent evidence shows that cannabinoid receptors are expressed in cells of the reproductive system including endometrial stromal cells, ovaries, and sperm cells. Emerging and recent research suggests that the ECS may play a significant role in reproduction. The endocannabinoid ligands anandamide and 2-arachidonoyl-glycerol are crucial for successful endometrium decidualization, placental development and embryo implantation. Alteration in cannabinoid receptors expression or in endocannabinoid homeostasis by excessive intake of cannabis during pregnancy is associated with negative pregnancy outcomes including preterm birth. The use of medicinal cannabis is becoming more widespread in Western countries, especially in people of reproductive age. Cannabis contains phytocannabinoids which modulate the ECS, and emerging evidence suggests that phytocannabinoids, through their action on cannabinoid receptors, may have a negative impact on fertility, pregnancy outcome and fetal health. In this mini-review, we highlight the recent advances in the field, which explore the role of endocannabinoids in early pregnancy and the effects of excessive intake of phytocannabinoids in pregnancy outcomes.