Table 2.

Changes in gene regulation in microorganisms and animals exposed to microgravity conditions.

Organisms and Conditions	Observations	Reference
U937 Cells (RCCS) and infection with Escherichia coli, mice (HU), gut bacteria, and investigation of intestinal immunity to Citrobacter rodentium	Suppressed MAPK pathway under s-µg in U937 cells. Downregulation of 25 transcripts and upregulation of 11 transcripts of the MAPK signaling pathway. In mice: suppression in the production of TNF and IL-6 in colon and spleen. Higher sensitivity against Citrobacter rodentium due to suppressed innate immune response.	[86]
Human colonic epithelial cell line, HT-29 (ATCC, HTB-38) infected with Salmonella typhimurium	Differences in gene expression between space- and ground-infected cells (among others, TNF signaling, NF-κB signaling, and cellular response to lipopolysaccharides).	[69]
HU mice, investigation of the gut biome	Dysbiosis followed after HU, which could be mitigated with 4-PBA, indicating that unloading leads to cellular stress.	[60]
Lactobacillus reuteri in RWV	These important probiotic bacteria respond with increased expression of stress genes.	[58]
Wheat and endophytic bacteria under s-µg	Change in root metabolism and secretion of metabolites. Change in bacteria composition of the rhizosphere.	[61]
Yersina pestis, HARV Cultivation	218 differentially regulated genes. Increased biofilm formation and reduced virulence (downregulation of virulence-associated genes).	[70]
Serratia marcescens and Drosophila melanogaster, HARV cultivation	Increased virulence of Serratia marcescens against Drosophila melanogaster.	[74]
Drosophila melanogaster on the ISS	Flies reared on the ISS showed smaller and weaker hearts, reduced sarcomeric and ECM gene expression, upregulated expression of proteasome subunit genes, and increased number of proteasomes.	[87]
Listeria monocytogenes (LSMMG)	Downregulation of virulence genes. Decreased heat and acid resistance, but increased cold resistance (upregulation of cold-stress genes).	[75]
Bacillus subtilis, Spaceflight	Increased mutation rate of rpoB.	[76]
Escherichia coli long-term HARV cultivation	Genome sequencing revealed an increased mutation rate, which resulted in the acquirement of antibiotic resistance.	[77]
Acinetobacter pittii and Staphylococcus aureus HARV cultivation	Increased rate of horizontal gene transfer.	[71]
Vibrio fischeri HARV cultivation	Impaired membrane stability, increased lipopolysaccharide production.	[81]
Knufia chersonesos (colorless and pigmented strain) HARV cultivation	Changes in the secretome, transcriptome, and proteome between 1g samples as well among the two strains. No increased stress response in the colorless strain.	[82]
Cryptococcus neoformans (melanized and colorless strain) on the ISS	Higher survival rate of melanized strains. Melanin acts as an antioxidant.	[83]
Eprymna scolopes HARV co-cultivation with Vibrio fischeri	Complex network of extrinsic/intrinsic apoptosis genes revealed; earlier and stronger expression of caspases.	[88]
Caenorhabditis elegans on the ISS	Downregulation of metabolism and cytoskeletal genes.	[89]
	Expression levels are regulated epigenetically.	[90]
Caenorhabditis elegans on the RCCS	Global upregulation of genes related to oxidative stress. Local overexpression prevented dysfunction but not increased lumen and permeability of the intestines.	[91]
	Expressional adaptations of the insulin signaling pathway in the intestines.	[92]
Mus musculus on the ISS	No estrous cycle discontinuation. No difference in the expression of genes related to steroidogenesis or mitochondrial cholesterol uptake.	[93]
	Thymi of ISS mice were smaller, with downregulated genes related to cell cycle control and chromosome organization.	[94]
	Erythrocyte production-related genes in the spleen were downregulated. No influence on gene expression in lymph nodes.	[95]

Abbreviations: 4-phenyl butyric acid (4-PBA); extracellular matrix (ECM); high aspect ratio vessels (HARV); hindlimb unloaded (HU); low-shear modelled microgravity (LSMMG); International Space Station (ISS); mitogen-activated protein kinase (MAPK); nuclear factor-kappa B (NF-κB); rotary cell culture system (RCCS); rotating wall vessel (RWV); tumor necrosis factor (TNF).