Impact of High Salt-Intake on a Natural Gut Ecosystem in Wildling Mice

Abstract

The mammalian holobiont harbors a complex and interdependent mutualistic gut bacterial community. Shifts in the composition of this bacterial consortium are known to be a key element in host health, immunity and disease. Among many others, dietary habits are impactful drivers for a potential disruption of the bacteria–host mutualistic interaction. In this context, we previously demonstrated that a high-salt diet (HSD) leads to a dysbiotic condition of murine gut microbiota, characterized by a decrease or depletion of well-known health-promoting gut bacteria. However, due to a controlled and sanitized environment, conventional laboratory mice (CLM) possess a less diverse gut microbiota compared to wild mice, leading to poor translational outcome for gut microbiome studies, since a reduced gut microbiota diversity could fail to depict the complex interdependent networks of the microbiome. Here, we evaluated the HSD effect on gut microbiota in CLM in comparison to wildling mice, which harbor a natural gut ecosystem more closely mimicking the situation in humans. Mice were treated with either control food or HSD and gut microbiota were profiled using amplicon-based methods targeting the 16S ribosomal gene. In line with previous findings, our results revealed that HSD induced significant loss of alpha diversity and extensive modulation of gut microbiota composition in CLM, characterized by the decrease in potentially beneficial bacteria from Firmicutes phylum such as the genera Lactobacillus, Roseburia, Tuzzerella, Anaerovorax and increase in Akkermansia and Parasutterella. However, HSD-treated wildling mice did not show the same changes in terms of alpha diversity and loss of Firmicutes bacteria as CLM, and more generally, wildlings exhibited only minor shifts in the gut microbiota composition upon HSD. In line with this, 16S-based functional analysis suggested only major shifts of gut microbiota ecological functions in CLM compared to wildling mice upon HSD. Our findings indicate that richer and wild-derived gut microbiota is more resistant to dietary interventions such as HSD, compared to gut microbiota of CLM, which may have important implications for future translational microbiome research.

Sex drives colonic mucin sialylation in wild mice

“…Changes in diet have been reported to have effects upon the glycosylation of mucins, independently of hormonal changes 30 . Furthermore, diet-induced changes in the microbiome also have the potential to influence mucin glycosylation 31 , 32 , and these aspects were not controlled for in our experiments. Together, these in vivo experiments suggest mucin sialylation is the most important aspect of the sex dependent differences of mucin glycosylation of laboratory animals, and also that mucin sulphation may be associated with systemic sex hormone signalling in male and female mice.…”

Sex drives colonic mucin sialylation in wild mice

“…Changes in diet have been reported to have effects upon the glycosylation of mucins, independently of hormonal changes [28]. Furthermore, diet-induced changes in the microbiome also have the potential to in uence mucin glycosylation [29], [30], and these aspects were not controlled for in our experiments. Together, these in vivo experiments suggest mucin sialylation is the most important aspect of the sex dependent differences of mucin glycosylation of laboratory animals, and also that mucin sulphation may be associated with systemic sex hormone signalling in male and female mice.…”

The Human Gut and Dietary Salt: The Bacteroides/Prevotella Ratio as a Potential Marker of Sodium Intake and Beyond

“…Studies by Kumar et al [35] reported a reduction in the abundance of both Firmicutes and Bacteroidetes in the gut of high-salt-fed rats compared to low-salt guts. In another animal study, loss of Lactobacillus and other beneficial genera in Firmicutes was not observed in the high-salt cohort of wilding mice [36], though it was observed in conventional laboratory mice. In a related study on risk factors of hypertension, HSD led to the reduction in beneficial Bacteroides (not B. fragilis) [37].…”