Gnotobiotic mice housing conditions critically influence the phenotype associated with transfer of faecal microbiota in a context of obesity.

OBJECTIVE: Faecal microbiota transplantation (FMT) in germ-free (GF) mice is a common approach to study the causal role of the gut microbiota in metabolic diseases. Lack of consideration of housing conditions post-FMT may contribute to study heterogeneity. We compared the impact of two housing strategies on the metabolic outcomes of GF mice colonised by gut microbiota from mice treated with a known gut modulator (cranberry proanthocyanidins (PAC)) or vehicle. DESIGN: High-fat high-sucrose diet-fed GF mice underwent FMT-PAC colonisation in sterile individual positive flow ventilated cages under rigorous housing conditions and then maintained for 8 weeks either in the gnotobiotic-axenic sector or in the specific pathogen free (SPF) sector of the same animal facility. RESULTS: Unexpectedly, 8 weeks after colonisation, we observed opposing liver phenotypes dependent on the housing environment of mice. Mice housed in the GF sector receiving the PAC gut microbiota showed a significant decrease in liver weight and hepatic triglyceride accumulation compared with control group. Conversely, exacerbated liver steatosis was observed in the FMT-PAC mice housed in the SPF sector. These phenotypic differences were associated with housing-specific profiles of colonising bacterial in the gut and of faecal metabolites. CONCLUSION: These results suggest that the housing environment in which gnotobiotic mice are maintained post-FMT strongly influences gut microbiota composition and function and can lead to distinctive phenotypes in recipient mice. Better standardisation of FMT experiments is needed to ensure reproducible and translatable results.

The postnatal window is critical for the development of sex-specific metabolic and gut microbiota outcomes in offspring.

The Developmental Origins of Health and Disease (DOHaD) concept has been proposed to explain the influence of environmental conditions during critical developmental stages on the risk of diseases in adulthood. The aim of this study was to compare the impact of the prenatal vs. postnatal environment on the gut microbiota in dams during the preconception, gestation and lactation periods and their consequences on metabolic outcomes in offspring. Here we used the cross-fostering technique, e.g. the exchange of pups following birth to a foster dam, to decipher the metabolic effects of the intrauterine versus postnatal environmental exposures to a polyphenol-rich cranberry extract (CE). CE administration to high-fat high-sucrose (HFHS)-fed dams improved glucose homeostasis and reduced liver steatosis in association with a shift in the maternal gut microbiota composition. Unexpectedly, we observed that the postnatal environment contributed to metabolic outcomes in female offspring, as revealed by adverse effects on adiposity and glucose metabolism, while no effect was observed in male offspring. In addition to the strong sexual dimorphism, we found a significant influence of the nursing mother on the community structure of the gut microbiota based on α-diversity and ß-diversity indices in offspring. Gut microbiota transplantation (GMT) experiments partly reproduced the observed phenotype in female offspring. Our data support the concept that the postnatal environment represents a critical window to influence future sex-dependent metabolic outcomes in offspring that are causally but partly linked with gut microbiome alterations.

Perspective: Nutritional Strategies Targeting the Gut Microbiome to Mitigate COVID-19 Outcomes.

More than a year has passed since the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection in the city of Wuhan in China's Hubei Province. Until now, few antiviral medications (e.g., remdesivir) or drugs that target inflammatory complications associated with SARS-CoV2 infection have been considered safe by public health authorities. By the end of November 2020, this crisis had led to >1 million deaths and revealed the high susceptibility of people with pre-existing comorbidities (e.g., obesity, diabetes, coronary heart disease, hypertension) to suffer from a severe form of the disease. Elderly people have also been found to be highly susceptible to SARS-CoV2 infection and morbidity. Gastrointestinal manifestations and gut microbial alterations observed in SARS-CoV2-infected hospitalized patients have raised awareness of the potential role of intestinal mechanisms in increasing the severity of the disease. It is therefore critically important to find alternative or complementary approaches, not only to prevent or treat the disease, but also to reduce its growing societal and economic burden. In this review, we explore potential nutritional strategies that implicate the use of polyphenols, probiotics, vitamin D, and ω-3 fatty acids with a focus on the gut microbiome, and that could lead to concrete recommendations that are easily applicable to both vulnerable people with pre-existing metabolic comorbidities and the elderly, but also to the general population.

Potential therapeutic applications of the gut microbiome in obesity: from brain function to body detoxification.

The prevalence of obesity is rising every year and associated comorbidities such as cardiovascular diseases are among the leading causes of death worldwide. The gut microbiota has recently emerged as a potential target for therapeutic applications to prevent and treat those comorbidities. In this review, we focus on three conditions related to obesity in which the use of gut microbiota modulators could have benefits; mood disorders, eating behaviors, and body detoxification of persistent organic pollutants (POPs). On one hand, modulation of gut-derived signals to the brain in a context of obesity is involved in the development of neuroinflammation and can subsequently alter behaviors. An altered gut microbiome could change these signals and alleviate their consequences. On the other hand, obesity is associated with an increased accumulation of lipophilic contaminants, such as POPs. Targeting the microbiota could help body detoxication by reducing bioavailability, enhancing degradation by bioremediation or their excretion through the enterohepatic circulation. Thus, a supplementation of prebiotics, probiotics, or synbiotics could represent a complementary strategy to current ones, such as medication and lifestyle modifications, to decrease depression, alter eating behaviors, and lower body burden of pollutants considering the actual obesity epidemic our society is facing.

Wild blueberry proanthocyanidins shape distinct gut microbiota profile and influence glucose homeostasis and intestinal phenotypes in high-fat high-sucrose fed mice.

Blueberries are a rich source of polyphenols, widely studied for the prevention or attenuation of metabolic diseases. However, the health contribution and mechanisms of action of polyphenols depend on their type and structure. Here, we evaluated the effects of a wild blueberry polyphenolic extract (WBE) (Vaccinium angustifolium Aiton) on cardiometabolic parameters, gut microbiota composition and gut epithelium histology of high-fat high-sucrose (HFHS) diet-induced obese mice and determined which constitutive polyphenolic fractions (BPF) was responsible for the observed effects. To do so, the whole extract was separated in three fractions, F1) Anthocyanins and phenolic acids, F2) oligomeric proanthocyanidins (PACs), phenolic acids and flavonols (PACs degree of polymerization DP < 4), and F3) PACs polymers (PACs DP > 4) and supplied at their respective concentration in the whole extract. After 8 weeks, WBE reduced OGTT AUC by 18.3% compared to the HFHS treated rodents and the F3 fraction  contributed the most to this effect. The anthocyanin rich F1 fraction did not reproduce this response. WBE and the BPF restored the colonic mucus layer. Particularly, the polymeric PACs-rich F3 fraction increased the mucin-secreting goblet cells number. WBE caused a significant 2-fold higher proportion of Adlercreutzia equolifaciens whereas oligomeric PACs-rich F2 fraction increased by 2.5-fold the proportion of Akkermansia muciniphila. This study reveals the key role of WBE PACs in modulating the gut microbiota and restoring colonic epithelial mucus layer, providing a suitable ecological niche for mucosa-associated symbiotic bacteria, which may be crucial in triggering health effects of blueberry polyphenols.