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The prevalence of overweight and obesity is on the rise around the world, not only in the West, but also in Asian countries. South Asian countries in particular are experiencing a rapid increase in overweight and obesity, that coexists with the rapid increase in non-communicable diseases linked to obesity such as diabetes and cardiovascular disease than any other country in Asia. The phenomena observed in South Asian countries are due to the size of the population, the ageing of the population, the high degree of urbanization and the lifestyle changes in favor of increased energy consumption and reduced physical activity. The imbalance between energy consumption and energy expenditure results in the development of a positive energy balance that, over time, accumulates in higher body fat. South Asians were reported to have a more unfavorable body composition with a higher percentage of body fat than Caucasians with an equivalent BMI. Body composition is a major determinant of resting energy expenditure. It has been reported that South Asians have a lower resting energy expenditure than Caucasians with the same BMI. Resting energy expenditure accounts for the majority of total daily energy expenditure and, therefore, plays a crucial role in achieving the balance between energy intake and expenditure.

We utilised a ground-based microgravity hindlimb unloading (HU) mouse model to elucidate the gut microbiota bacterial changes in mice under a simulated microgravity environment. Four-month-old, male C57/Bl6 mice were randomly divided into ground-based controls and the HU groups and kept under controlled environmental conditions. For the microgravity environment, the mice were suspended in special cages individually for 20 days. At the end of the suspension, the mice were sacrificed; gut dissections were performed, followed by a metagenomic analysis of bacterial species, which was carried out by extracting DNA and 16S rRNA analysis. The results revealed that the gut bacterial communities of mice under gravity and microgravity were different. Notably, our findings revealed differences in the bacterial community structure. Around 449 bacterial OTUs were specific to mice kept under normal gravity versus 443 bacterial OTUs under microgravity conditions. In contrast, 694 bacterial OTUs were common to both groups. When the relative abundance of taxa was analyzed, Bacteroidetes dominated the gut (64.7%) of normal mice. Conversely, mice in the microgravity environment were dominated by Firmicutes (42.7%), and the relative abundance of Bacteroidetes differed significantly between the two groups (p < 0.05). The distribution of Muribaculaceae between normal mice versus microgravity mice was significantly different, at 62% and 36.4%, respectively (p < 0.05). Furthermore, a significant decrease in 11 bacteria was observed in mice under simulated microgravity, including Akkermansia muciniphila, Eubacterium coprostanoligenes, Bacteroides acidifaciens, Clostridium leptum, Methylorubrum extorquens, Comamonas testosterone, Desulfovibrio fairfieldensis, Bacteroides coprocola, Aerococcus urinaeequi, Helicobacter hepaticus, and Burkholderiales. Further studies are needed to elucidate gut bacterial metabolites of these identified bacterial species in microgravity conditions and normal environment. Notably, the influence of these metabolites on obesity, neuroprotection, musculoskeletal and cardiovascular dysfunction, longevity, inflammation, health, and disease in astronauts ought to be investigated and will be important in developing procedures against adverse effects in astronauts following space travel.

The altered gut microbes of astronauts during space travel may contribute to health issues after their return to Earth. Previously, an association between the elevated endoplasmic reticulum (ER) stress and gut microbial dysbiosis has been described. Herein, we induced gut microbial changes in mice under a simulated microgravity environment in an established model of hindlimb unloaded (HU) mice. The intestinal metabolomic profiles under microgravity conditions using the HU model were examined, along with the potential role of 4-phenylbutyric acid (4-PBA), a potent ER stress inhibitor. For a microgravity environment, the mice were suspended in special cages individually for three weeks. Mice were sacrificed, and gut dissections were performed, followed by amplicon sequencing analysis of bacterial species via DNA extraction and 16S rRNA analysis. The results indicate that the gut bacterial communities of mice differed under gravity and microgravity conditions. Principal component analyses revealed differences in the bacterial community structure in all groups. Around 434 operational taxonomic units (OTUs) were specific to mice seen in controls, while 620 OTUs were specific to HU mice. Additionally, 321 bacterial OTUs were specific to HU mice treated with 4-PBA. When the relative abundance of taxa was analyzed, Bacteroidetes dominated the gut of control and HU mice treated with 4-PBA.. In contrast, the untreated HU mice were dominated by Firmicutes. At the genus level, a reduction in beneficial species of Akkermansia and Lactobacillus was observed in HU but not the unloaded-treated and control mice. Furthermore, an increase in the relative abundance of Lachnospiraceae and Enterorhabdus , associated with inflammation, was observed in HUmice but not in controls and unloaded-treated mice. Following treatment with 4-PBA, the ratio of Firmicutes to Bacteroidetes was restored in unloaded-treated mice, comparable to controls. Of note, beneficial microbes such as Akkermansia and Lactobacillus were observed in unloaded-treated mice but not or in lesser relative abundance in HU mice. Nonetheless, microbial diversity was reduced in unloaded-treated mice compared to controls, and future studies are needed to mitigate this finding. These may comprise the addition of pre-/pro- and postbiotic species in the diet to increase microbial diversity. Overall, the findings suggest that 4-PBA, a potent ER stress inhibitor, may have therapeutic value in treating patients on prolonged bed rest or astronauts during spaceflight.

Microgravity environments are known to cause a plethora of stressors to astronauts. Recently, it has become apparent that gut microbiome composition of astronauts is altered following space travel, and this is of significance given the important role of the gut microbiome in human health. Other changes observed in astronauts comprise reduced muscle strength and bone fragility, visual impairment, endothelial dysfunction, metabolic changes, behavior changes due to fatigue or stress and effects on mental well-being. However, the effects of microgravity on angiogenesis, as well as the connection with the gut microbiome are incompletely understood. Here, the potential association of angiogenesis with visual impairment, skeletal muscle and gut microbiome is proposed and explored. Furthermore, metabolites that are effectors of angiogenesis are deliberated upon along with their connection with gut bacterial metabolites. Targeting and modulating the gut microbiome may potentially have a profound influence on astronaut health, given its impact on overall human health, which is thus warranted given the likelihood of increased human activity in the solar system, and the determination to travel to Mars in future missions.

Patients with chronic obstructive pulmonary disease (COPD) present with an advanced form of age-related muscle loss or sarcopenia. Among multiple pathomechanisms of sarcopenia, neuromuscular junction (NMJ) degradation may be of primary relevance. We evaluated the circulating biomarkers of NMJ degradation, including c-terminal agrin fragment -22 (CAF22), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) as predictors of sarcopenia in COPD during pulmonary rehabilitation (PR). Male, 61-77-year-old healthy controls and patients of COPD ( n = 77-84/group) were recruited for measurements of circulating CAF22, BDNF, and GDNF levels. Functional assessment and measurements of plasma biomarkers were performed at diagnosis and following six months of PR. CAF22 levels were elevated while BDNF and GDNF levels were reduced in COPD patients at diagnosis, which were incompletely restored to normal levels following PR. These biomarkers showed varying degrees of associations with indexes of sarcopenia and functional recovery during PR. Logistic regression revealed that the combined use of three biomarkers enhanced the diagnostic accuracy of sarcopenia better than single biomarkers. Altogether, measurements of plasma CAF22, BDNF, and GDNF may be helpful for the accurate diagnosis of sarcopenia and functional capacity in COPD during PR.