Lactobacillus delbrueckii subsp. bulgaricus Alleviates Acute Injury in Hypoxic Mice.

Acute mountain sickness (AMS) is a common ailment in high-altitude areas caused by the body's inadequate adaptation to low-pressure, low-oxygen environments, leading to organ edema, oxidative stress, and impaired intestinal barrier function. The gastrointestinal tract, being the first to be affected by ischemia and hypoxia, is highly susceptible to injury. This study investigates the role of Lactobacillus delbrueckii subsp. bulgaricus in alleviating acute hypoxic-induced intestinal and tissue damage from the perspective of daily consumed lactic acid bacteria. An acute hypoxia mouse model was established to evaluate tissue injury, oxidative stress, inflammatory responses, and intestinal barrier function in various groups of mice. The results indicate that strain 4L3 significantly mitigated brain and lung edema caused by hypoxia, improved colonic tissue damage, and effectively increased the content of tight junction proteins in the ileum, reducing ileal permeability and alleviating mechanical barrier damage in the intestines due to acute hypoxia. Additionally, 4L3 helped to rebalance the intestinal microbiota. In summary, this study found that Lactobacillus delbrueckii subsp. bulgaricus strain 4L3 could alleviate acute intestinal damage caused by hypoxia, thereby reducing hypoxic stress. This suggests that probiotic lactic acid bacteria that exert beneficial effects in the intestines may alleviate acute injury under hypoxic conditions in mice, offering new insights for the prevention and treatment of AMS.

Effects of intestinal flora on the pharmacokinetics and pharmacodynamics of aspirin in high-altitude hypoxia.

Since hypobaric hypoxia significantly affects metabolic characteristics of intestinal flora, which plays an important role in the biotransformation of aspirin, high altitudes may influence the pharmacokinetics and therapeutic effects of aspirin in the intestines. In the present study, to test alterations of intestinal microbiota at high altitude comparing to that at low altitude, we analyzed rat feces from plain group and high-altitude group by 16S rRNA analysis. To detect concentrations of aspirin and salicylic acid, we established a reliable liquid chromatography tandem mass spectrometry method to measure aspirin and salicylic acid concentrations in fecal suspensions and plasma. Our study found that the plateau hypoxic environment caused a significant increase in Bacteroides in rat feces, while Corynebacterium, Prevotella, and Coprococcus were declined. In addition, compared with the plain group, the metabolic activity of fecal suspensions from the plateau group on aspirin was significantly reduced. More importantly, these changes in the intestinal microbiota led to increasing absorption of aspirin in the rats after rapidly ascent to the plateau, and a reduction in the pharmacodynamic index TXB2, which would possibly result in bleeding. In conclusion, our research provides new ideas for changes in plateau pharmacokinetics, and then guide the corresponding reduction in aspirin dose for the population quickly entering the plateau.

Associations between the gut microbiota and host responses to high altitude.

Hypobaric hypoxia and dietary protein and fat intakes have been independently associated with an altered gastrointestinal (GI) environment and gut microbiota, but little is known regarding host-gut microbiota interactions at high altitude (HA) and the impact of diet macronutrient composition. This study aimed to determine the effect of dietary protein:fat ratio manipulation on the gut microbiota and GI barrier function during weight loss at high altitude (HA) and to identify associations between the gut microbiota and host responses to HA. Following sea-level (SL) testing, 17 healthy males were transported to HA (4,300 m) and randomly assigned to consume provided standard protein (SP; 1.1 g·kg-1·day-1, 39% fat) or higher protein (HP; 2.1 g·kg-1·day-1, 23% fat) carbohydrate-matched hypocaloric diets for 22 days. Fecal microbiota composition and metabolites, GI barrier function, GI symptoms, and acute mountain sickness (AMS) severity were measured. Macronutrient intake did not impact fecal microbiota composition, had only transient effects on microbiota metabolites, and had no effect on increases in small intestinal permeability, GI symptoms, and inflammation observed at HA. AMS severity was also unaffected by diet but in exploratory analyses was associated with higher SL-relative abundance of Prevotella, a known driver of interindividual variability in human gut microbiota composition, and greater microbiota diversity after AMS onset. Findings suggest that the gut microbiota may contribute to variability in host responses to HA independent of the dietary protein:fat ratio but should be considered preliminary and hypothesis generating due to the small sample size and exploratory nature of analyses associating the fecal microbiota and host responses to HA. NEW & NOTEWORTHY This study is the first to examine interactions among diet, the gut microbiota, and host responses to weight loss at high altitude (HA). Observed associations among the gut microbiota, weight loss at HA, and acute mountain sickness provide evidence that the microbiota may contribute to variability in host responses to HA. In contrast, dietary protein:fat ratio had only minimal, transient effects on gut microbiota composition and bacterial metabolites which were likely not of clinical consequence.

Alteration of predominant gastrointestinal flora and oxidative damage of large intestine under simulated hypobaric hypoxia.

Hypobaric hypoxia is an immediate and crucial starting mechanism of acute mountain sickness included with some non-specific gastrointestinal (GI) complications. To study the effect of hypoxia on GI microflora and its upshot to this system, male albino rats were exposed to 55 kPa (air pressure ~ 4872.9 m altitude) consecutively 30 days for 8 hours/day. The different indicator group of large intestinal microbial populations were enumerated and correlated with the levels of antioxidant indicators like catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of large intestinal epithelial cells. In addition, the histological study was performed by haematoxylin eosin (HE), periodic acid schiff staining (PAS) and scanning electron microscopy (SEM). It was observed that the density of total aerobes (104 folds) significantly (p < 0.05) decreased but the population of total anaerobes (209 folds) and Escherichia coli (125 folds) elevated after 30 days of hypoxic stress. The strict anaerobes like Bifidobacterium spp. (3 folds), Bacteroides spp. (134 folds), Lactobacillus spp. (7 folds) and other selected obligate anaerobes like Clostridium perfringens (40 folds), Peptostreptococcus spp. (21 folds) increased in respect to their control population. The growth direction index (GDI) of anaerobic populations was positive and correlated with gas formation aptitude. The activities of CAT and SOD in the large intestinal epithelia decreased significantly (p < 0.05) and GSH/GSSG pool turned into oxidized state with higher MDA (p < 0.05) formation. Histological study revealed the necrotized epithelial layer with higher lymphocytes infiltration in lamina propia accompanied by reduction of acidic mucins secreting goblet cells. From this experiment, it can be hypothesized that high altitude induced hypoxia manipulated the bacterial imprint and damaged the epithelial barrier of the large intestine which may cause systemic infection.