Human milk oligosaccharide 2'-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice.

OBJECTIVE: To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system. RESULTS: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2'FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera Akkermansia and Bacteroides, different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice. CONCLUSION: Our results show that the HMO 2'FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders.

The impact of daily supplementation with rhamnogalacturonan-I on the gut microbiota in healthy adults: A randomized controlled trial.

Pectin and its derivatives have been shown to modulate immune signaling as well as gut microbiota in preclinical studies, which may constitute the mechanisms by which supplementation of specific pectic polysaccharides confers protection against viral respiratory infections. In a double-blind, placebo-controlled rhinovirus (RV16) challenge study, healthy volunteers were randomized to consume placebo (0.0 g/day) (N = 46), low-dose (0.3 g/day) (N = 49) or high-dose (1.5 g/day) (N = 51) of carrot derived rhamnogalacturonan-I (cRG-I) for eight weeks and they were subsequently challenged with RV-16. Here, the effect of 8-week cRG-I supplementation on the gut microbiota was studied. While the overall gut microbiota composition in the population was generally unaltered by this very low dose of fibre, the relative abundance of Bifidobacterium spp. (mainly B. adolescentis and B. longum) was significantly increased by both doses of cRG-1. Moreover, daily supplementation of cRG-I led to a dose-dependent reduction in inter- and intra-individual microbiota heterogeneity, suggesting a stabilizing effect on the gut microbiota. The severity of respiratory symptoms did not directly correlate with the cRG-I-induced microbial changes, but several dominant groups of the Ruminococcaceae family and microbiota richness were positively associated with a reduced and hence desired post-infection response. Thus, the present results on the modulation of the gut microbiota composition support the previously demonstrated immunomodulatory and protective effect of cRG-I during a common cold infection.

Case report: Aberrant fecal microbiota composition of an infant diagnosed with prolonged intestinal botulism.

BACKGROUND: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months. CASE PRESENTATION: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time. CONCLUSION: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.

Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort.

Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of Bifidobacterium and Escherichia/Shigella spp. and a higher proportion of Bacteroides. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.IMPORTANCEAllergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT00298337).

Hirsutella sinensis polysaccharides and Parabacteroides goldsteinii reduce lupus severity in imiquimod-treated mice.

BACKGROUND: The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet. METHODS: We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus. RESULTS: The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not influence gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues. CONCLUSIONS: Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases.