•Older people are often malnourished and susceptible to develop lung diseases.•Ageing is associated with dysbiotic microbiota and alteration of the gut-lung axis.•Nutrition is an accessible lever ...affecting microbiota and ageing of the lung.•Gut and lung microbiota represent key players in the maintenance of healthy lungs.•Gut and lung microbiota are potential targets against ageing-related lung disease.
Older people are at an increased risk of developing respiratory diseases such as chronic obstructive pulmonary diseases, asthma, idiopathic pulmonary fibrosis or lung infections. Susceptibility to these diseases is partly due to the intrinsic ageing process, characterized by genomic, cellular and metabolic hallmarks and immunosenescence, and is associated with changes in the intestinal microbiota. Importantly, in the lungs, ageing is also associated with a dysbiosis and loss of resilience of the resident microbiota and alterations of the gut-lung axis. Notably, as malnutrition is often observed in the elderly, nutrition is one of the most accessible modifiable factors affecting both senescence and microbiota. This article reviews the changes affecting the lung and its resident microbiota during ageing, as well as the interconnections between malnutrition, senescence, microbiota, gut-lung axis and respiratory health. As the communication along the gut-lung axis becomes more permissive with ageing, this review also explores the evidence that the gut and lung microbiota are key players in the maintenance of healthy lungs, and as such, are potential targets for nutrition-based preventive strategies against lung disease in elderly populations.
Evidence suggests that gut microbiota composition and diversity can be a determinant of skeletal muscle metabolism and functionality. This is true in catabolic (sarcopenia and cachexia) or anabolic ...(exercise or in athletes) situations. As gut microbiota is known to be causal in the development and worsening of metabolic dysregulation phenotypes such as obesity or insulin resistance, it can regulate, at least partially, skeletal muscle mass and function. Skeletal muscles are physiologically far from the gut. Signals generated by the gut due to its interaction with the gut microbiome (microbial metabolites, gut peptides, lipopolysaccharides, and interleukins) constitute links between gut microbiota activity and skeletal muscle and regulate muscle functionality via modulation of systemic/tissue inflammation as well as insulin sensitivity. The probiotics able to limit sarcopenia and cachexia or promote health performances in rodents are mainly lactic acid bacteria and bifidobacteria. In humans, the same bacteria have been tested, but the scarcity of the studies, the variability of the populations, and the difficulty to measure accurately and with high reproducibility muscle mass and function have not allowed to highlight specific strains able to optimize muscle mass and function. Further studies are required on more defined population, in order to design personalized nutrition. For elderly, testing the efficiency of probiotics according to the degree of frailty, nutritional state, or degree of sarcopenia before supplementation is essential. For exercise, selection of probiotics capable to be efficient in recreational and/or elite athletes, resistance, and/or endurance exercise would also require further attention. Ultimately, a combination of strategies capable to optimize muscle functionality, including bacteria (new microbes, bacterial ecosystems, or mix, more prone to colonize a specific gut ecosystem) associated with prebiotics and other ‘traditional’ supplements known to stimulate muscle anabolism (e.g. proteins), could be the best way to preserve muscle functionality in healthy individuals at all ages or patients.
Improvements in our knowledge of the gut microbiota have broadened our vision of the microbes associated with the intestine. These microbes are essential actors and protectors of digestive and ...extra-digestive health and, by extension, crucial for human physiology. Similar reconsiderations are currently underway concerning the endogenous microbes of the lungs, with a shift in focus away from their involvement in infections toward a role in physiology. The discovery of the lung microbiota was delayed by the long-held view that the lungs of healthy individuals were sterile and by sampling difficulties. The lung microbiota has a low density, and the maintenance of small numbers of bacteria seems to be a critical determinant of good health. This review aims to highlight how knowledge about the lung microbiota can change our conception of lung physiology and respiratory health. We provide support for this point of view with knowledge acquired about the gut microbiota and intestinal physiology. We describe the main characteristics of the lung microbiota and its functional impact on lung physiology, particularly in healthy individuals, after birth, but also in asthma. We describe some of the physiological features of the respiratory tract potentially favoring the installation of a dysbiotic microbiota. The gut microbiota feeds and matures the intestinal epithelium and is involved in immunity, when the principal role of the lung microbiota seems to be the orientation and balance of aspects of immune and epithelial responsiveness. This implies that the local and remote effects of bacterial communities are likely to be determinant in many respiratory diseases caused by viruses, allergens or genetic deficiency. Finally, we discuss the reciprocal connections between the gut and lungs that render these two compartments inseparable.
Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory ...bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection.
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•Influenza alters the production of SCFAs by the gut microbiota•The dysbiotic microbiota transfers susceptibility to respiratory bacterial infection•Supplementation with acetate restores the killing activity of alveolar macrophages•Activation of the SCFA receptor FFAR2 protects against bacterial superinfection
Sencio et al. provide insights into the mechanisms that underlie bacterial superinfection post-influenza. The authors demonstrate that influenza infection remotely alters the production of short-chain fatty acids (SCFAs) by the gut microbiota. Supplementation with acetate or pharmacological activation of the SCFA receptor FFAR2 reduces susceptibility to secondary bacterial infection.
The first objective of infant formulas is to ensure the healthy growth of neonates and infants, as the sole complete food source during the first months of life when a child cannot be breastfed. ...Beyond this nutritional aspect, infant nutrition companies also try to mimic breast milk in its unique immuno-modulating properties. Numerous studies have demonstrated that the intestinal microbiota under the influence of diet shapes the maturation of the immune system and influences the risk of atopic diseases in infants. A new challenge for dairy industries is, therefore, to develop infant formulas inducing the maturation of immunity and the microbiota that can be observed in breastfed delivered vaginally, representing reference infants.
,
DSM 17938,
(BC50),
Bb12,
(CECT5716), and
GG (LGG) are some of the probiotics added to infant formula, according to a literature review of the past 10 years. The most frequently used prebiotics in published clinical trials are fructo-oligosaccharides (FOSs), galacto-oligosaccharides (GOSs), and human milk oligosaccharides (HMOs). This review sums up the expected benefits and effects for infants of pre-, pro-, syn-, and postbiotics added to infant formula regarding the microbiota, immunity, and allergies.
is a major member of the Firmicutes phylum and one of the most abundant bacteria in the healthy human microbiota.
depletion has been reported in several intestinal disorders, and more consistently in ...Crohn's disease (CD) patients. Despite its importance in human health, only few microbiological studies have been performed to isolate novel
strains in order to better understand the biodiversity and physiological diversity of this beneficial commensal species. In this study, we described a protocol to isolate novel
strains from feces of healthy volunteers as well as a deep molecular and metabolic characterization of these isolated strains. These
strains were classified in two phylogroups and three clusters according to 16S rRNA sequences and results support that they would belong to two different genomospecies or genomovars as no genome sequencing has been performed in this work. Differences in enzymes production, antibiotic resistance and immunomodulatory properties were found to be strain-dependent. So far, all
isolates share some characteristic such as (i) the lack of epithelial cells adhesion, plasmids, anti-microbial, and hemolytic activity and (ii) the presence of DNAse activity. Furthermore, Short Chain Fatty Acids (SCFA) production was assessed for the novel isolates as these products influence intestinal homeostasis. Indeed, the butyrate production has been correlated to the capacity to induce IL-10, an anti-inflammatory cytokine, in peripheral blood mononuclear cells (PBMC) but not to the ability to block IL-8 secretion in TNF-α-stimulated HT-29 cells, reinforcing the hypothesis of a complex anti-inflammatory pathway driven by
. Altogether, our results suggest that some
strains could represent good candidates as next-generation probiotic.
Lactic acid bacteria (LAB) are representative members of multiple ecosystems on earth, displaying dynamic interactions within animal and plant kingdoms in respect with other microbes. This highly ...heterogeneous phylogenetic group has coevolved with plants, invertebrates, and vertebrates, establishing either mutualism, symbiosis, commensalism, or even parasitism-like behavior with their hosts. Depending on their location and environment conditions, LAB can be dominant or sometimes in minority within ecosystems. Whatever their origins and relative abundance in specific anatomic sites, LAB exhibit multifaceted ecological and functional properties. While some resident LAB permanently inhabit distinct animal mucosal cavities, others are provided by food and may transiently occupy the gastrointestinal tract. It is admitted that the overall gut microbiome has a deep impact on health and diseases. Here, we examined the presence and the physiological role of LAB in the healthy human and several animal microbiome. Moreover, we also highlighted some dysbiotic states and related consequences for health, considering both the resident and the so-called "transionts" microorganisms. Whether LAB-related health effects act collectively or follow a strain-specificity dogma is also addressed. Besides the highly suggested contribution of LAB to interplay with immune, metabolic, and even brain-axis regulation, the possible involvement of LAB in xenobiotic detoxification processes and metal equilibrium is also tackled. Recent technological developments such as functional metagenomics, metabolomics, high-content screening and design
and
experimental models now open new horizons for LAB as markers applied for disease diagnosis, susceptibility, and follow-up. Moreover, identification of general and more specific molecular mechanisms based on antioxidant, antimicrobial, anti-inflammatory, and detoxifying properties of LAB currently extends their selection and promising use, either as probiotics, in traditional and functional foods, for dedicated treatments and mostly for maintenance of normobiosis and homeostasis.
Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. ...Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.
Inflammatory bowel diseases (IBD) are characterized by low proportions of F. prausnitzii in the gut microbiome. This commensal bacterium exhibits anti-inflammatory effects through still unknown mechanisms. Stable monoassociated rodents are actually not a reproducible model to decipher F. prausnitzii protective effects. We propose a new gnotobiotic rodent model providing mechanistic clues. In this model, F. prausnitzii exhibits protective effects against an acute colitis and a protective metabolic profile is linked to its presence along the digestive tract. We identified a molecule, salicylic acid, directly involved in the protective effect of F. prausnitzii. Targeting its metabolic pathways could be an attractive therapeutic strategy in IBD.
Along with respiratory tract disease
, viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an ...experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders. In IAV-infected mice, the signs of intestinal injury and inflammation, altered gene expression, and compromised intestinal barrier functions peaked on day 7 postinfection. As a likely result of bacterial component translocation, gene expression of inflammatory markers was upregulated in the liver. These changes occurred concomitantly with an alteration of the composition of the gut microbiota and with a decreased production of the fermentative, gut microbiota-derived products short-chain fatty acids (SCFAs). Gut inflammation and barrier dysfunction during influenza were not attributed to reduced food consumption, which caused in part gut dysbiosis. Treatment of IAV-infected mice with SCFAs was associated with an enhancement of intestinal barrier properties, as assessed by a reduction in the translocation of dextran and a decrease in inflammatory gene expression in the liver. Lastly, SCFA supplementation during influenza tended to reduce the translocation of the enteric pathogen Salmonella enterica serovar Typhimurium and to enhance the survival of doubly infected animals. Collectively, influenza virus infection can remotely impair the gut's barrier properties and trigger secondary enteric infections. The latter phenomenon can be partially countered by SCFA supplementation.
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