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The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2 nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14 th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2 nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

A variety of species of bacteria are known to colonize human tumours 1-11 , proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment 12-14 . However, it is not known whether antigens derived from intracellular bacteria are presented by the human leukocyte antigen class I and II (HLA-I and HLA-II, respectively) molecules of tumour cells, or whether such antigens elicit a tumour-infiltrating T cell immune response. Here we used 16S rRNA gene sequencing and HLA peptidomics to identify a peptide repertoire derived from intracellular bacteria that was presented on HLA-I and HLA-II molecules in melanoma tumours. Our analysis of 17 melanoma metastases (derived from 9 patients) revealed 248 and 35 unique HLA-I and HLA-II peptides, respectively, that were derived from 41 species of bacteria. We identified recurrent bacterial peptides in tumours from different patients, as well as in different tumours from the same patient. Our study reveals that peptides derived from intracellular bacteria can be presented by tumour cells and elicit immune reactivity, and thus provides insight into a mechanism by which bacteria influence activation of the immune system and responses to therapy.

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients' smoking status, and the response to immunotherapy., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Dead Sea climatotherapy (DSC) is a well-established therapeutic modality for the treatment of several diseases, including atopic dermatitis. Skin microbiome studies have shown that skin microbiome diversity is anticorrelated with both atopic dermatitis severity and concurrent Staphylococcus aureus overgrowth. This study aimed to determine whether DSC induces skin microbiome changes concurrent with clinical improvements in atopic dermatitis. We sampled 35 atopic dermatitis patients and ten healthy controls on both the antecubital and popliteal fossa. High-resolution microbial community profiling was attained by sequencing multiple regions of the 16S rRNA gene. Dysbiosis was observed in both lesional and nonlesional sites, which was partially attenuated following treatment. Severe AD skin underwent the most significant community shifts, and Staphylococcus epidermidis, Streptococcus mitis and Micrococcus luteus relative abundance were significantly affected by Dead Sea climatotherapy. Our study highlights the temporal shifts of the AD skin microbiome induced by Dead Sea climatotherapy and offers potential explanations for the success of climatotherapy on a variety of skin diseases, including AD., (© 2019 American Society for Photobiology.)

Dead Sea climatotherapy (DSC) is a therapeutic modality for a variety of chronic skin conditions, yet there has been scarce research on the relationship between the cutaneous microbiota and disease states in response to DSC. We characterized the skin bacterial and fungal microbiome of healthy volunteers who underwent DSC. Bacterial community diversity remained similar before and after treatment, while fungal diversity was significantly reduced as a result of the treatment. Individuals showed greater inter-individual than temporal bacterial community variance, yet the opposite was true for fungal community composition. We further identified Malassezia as the genus driving temporal mycobiome variations. The results indicate that the microbiome remains stable throughout DSC, while the mycobiome undergoes dramatic community changes. The results of this study will serve as an important baseline for future investigations of microbiome and mycobiome temporal phenomena in diseased states.