Effects of Partial Gravity on Multi-system Mammalian Physiology: Microbiome and Related Systems

Lack of sleep is a persistent challenge to astronaut crews (Santy et al., 1988; Goel & Dinges, 2012), accompanied by disrupted circadian rhythms (Monk et al., 1998; Dijk et al., 2001; Mallis & DeRoshia, 2005). There is evidence of microgravity altering circadian rhythms in rodents as well (Fuller & Fuller, 2006; Casey et al., 2012). Importantly, a manned Mars mission also involves a Mars-specific challenge to circadian synchronization: a 24.65-hour light/dark cycle (Scheer et al., 2007; Barger et al., 2012). We and many others have found disruptions of circadian rhythms contribute to a number of health issues ranging from metabolic (Turek et al., 2005; Arble et al., 2009) to reproductive (Summa et al., 2012) and GI inflammation (Summa et al., 2013; Preuss et al., 2008). Both the spaceflight environment (Roda et al., 2013) and on-ground circadian disrupted environments (Knuttson & Boggild, 2010; Konturek et al., 2011) are known to increase markers of gastrointestinal inflammatory diseases in humans and are associated with risks of altered gut microbial community (Voorhies & Lorenzi, 2016). Recently, we have demonstrated for the first time that environmental perturbation of circadian organization in mice leads to dysbiosis (Voigt et al., 2014), which is exacerbated by feeding mice a high-fat, high-sugar (“Western” diet). A role of gut microbiota in mammalian physical and psychological health beyond gastrointestinal inflammatory diseases has also been increasingly appreciated. Our preliminary study using samples from a previous Rodent Research mission (RR-1) has indicated a spaceflight-specific shift in gut microbiota (Figure A), although the influence of partial gravity, particularly the Martian gravity, remains unknown. Also, in many cases, circadian disruption can act as a “second hit” that exacerbates the effects of physiologically and/or psychiatrically challenging conditions. We therefore hypothesize that challenges in circadian organization induced by the Martian light/dark cycle may interact microgravity or partial gravity to alter microbiota in the GI. These alterations may be significant factors in the adaptation of multiple physiological systems to prolonged space travel as well as upon landing on Mars.