1,759 research outputs found
Modulating the structure and function of the human gut microbiota through diet: a metagenomics insight
No full textThe human gut microbiota has evolved in close partnership with host physiology and immune function. Although genetics plays some role in gut microbiota phylogenetic structure, environmental influences appear to govern the successional development of the gut microbiota from low species diversity in early life to the climax microbial communities in adulthood and gut microbiota senescence in old age. Of the environmental influences, diet not only determines community structure in terms of microbial relative abundance but may also determine species presence and absence, and how their functional activities impact on host health. Recent metagenomic studies from populations with very different habitual diets and living in very different regions of the world, have shown that diet, especially the relative proportions of whole plant foods, dietary fiber and polyphenols on the one hand, and refined carbohydrates, sugars, animal protein and fat on the other, can drive very distinct gut microbiota profiles, and that these divergent community structures impact on host:microbiota metabolic and immunological interactions influencing the risk of human disease (Fava et al., 2006; Tuohy et al., 2009, Conterno et al., 2011). De Filippo et al (2010) showed that the gut microbiota of children growing up in rural Burkina Faso following a low energy, high whole plant food, traditional African diet differed markedly from children growing up in urban Florence following a typical modern, Western style diet. Our more recent observations confirm the impact of dietary change or urbanisation on gut microbiota structure and also on the functional potential of the gut microbiome, with major differences in KEGG modules between African and European children. These differences appear to be driven largely by dietary fiber and animal protein/fat. We know from animals studies that fermentable fiber and prebiotics reduce the risk of metabolic disease and obesity (Arora et al., 2012), and similarly, that the type and quantity of both carbohydrate and fat in human diets can impact on microbiota composition and activity (Fava et al., 2012), implicating diet as a major driver of the aberrant gut microbiome associated with obesity and the diseases of obesity. These and similar observations raise the intriguing possibility that chronic human disease associated with overweight and obesity may be modulated by dietary supplementation with these functional foods (Conterno et al, 2011). Similarly, modulation of the gut microbiota impacts on microbial cross-talk with the mammalian immune system. In a collaborative study with the University of Reading, we have shown that dietary supplementation with the synbiotic (Bifidobacterium longum bv. infantis CCUG 52486 and glucooligosaccharides) reduces the severity of flue like symptoms in both the elderly and young adults. Moreover, using metagenomics we have shown that gut microbiota profiles differs significantly with age and that response to flue vaccine may in fact be reflected in gut microbial phylogenetic profiles. If microbiota profiles can be correlated directly with immune response, for example to vaccines or infections, then dietary modulating of these microbiota profiles e.g. using probiotics or prebiotics may also constitute a realistic and versatile population based strategy for reducing the risk and/or severity of important human infections like influenz
Intestinal microbiota, diet and health
No full textRecent omics level studies are confirming what pioneers in gut microbiology have been saying for some time, that diet:microbe interactions impact on human health and disease risk (Midtvedt, 1974; Rowland, 1988). The post genomics technologies of metagenomics and metabolomics are decoding the detailed cross-talk between the structure and function of the intestinal microbiome and host physiology, with diet:microbe interactions now shown to impact on the risk of cardio-metabolic disease, cancers, immune diseases and psychiatric disorders (Nicholson et al, 2012). The gut microbiota is becoming recognised as an important metabolic and immunological organ in its own right, intricately linked to the functioning of other organs most notably the liver, adipose tissue and the brain. Evidence mainly from animal studies describe important roles for gut microbiota metabolites and/or microbiota immunological regulation of metabolic and inflammatory pathways critical for maintenance of host defences. Indeed, such studies hint at common underlying pathological processes linking diet:microbe interactions in the gut with a spectrum of chronic diseases along the gut:liver:fat:brain axis. Indeed, different aspects of this gut:liver:fat:brain axis are currently receiving much attention for their role in obesity, the diseases of obesity (cardiovascular-disease, type 2 diabetes, non-alcoholic fatty liver disease, Alzheimer’s disease) and psychiatric conditions such as autism, Schizophrenia and importantly, depression. Many of these diseases are characterised by loss of metabolic homeostasis and unresolved systemic inflammation.
While the gut microbiota have been shown to produce toxic compounds for example trimethylamine-N-oxide and N-nitroso compounds derived from amino acid/protein fermentation n the gut, many microbial metabolites impact beneficially on host health, especially those which derive from the breakdown and fermentation of plant macromolecules, fibers and polyphenols. Short chain fatty acids and small phenolic compounds derived from colonic carbohydrate fermentation and plant polyphenol catabolism respectively, have been shown to play a critical role in establishment and maintenance of host defences, especially immune function (both within the gut and systemically) and gut barrier integrity. Moreover, plant fibers and polyphenols can influence the quantity of bile acids entering the distal ileum and colon, and also the profile of bile salt hydrolyzing bacteria therein, and thus may influence microbial involvement in the enterohepatic circulation of bile acids. Bile acids, apart from their role in regulating fat uptake are now being recognised for their important cell signalling role, acting as ligands for nuclear receptors like FXR, VDR, PXR, CAR and g-coupled receptors like TGR5, which in turn regulate inflammation, glucose and lipid metabolism, nutrient absorption, intestinal permeability and thermogenesis. Gut bacteria also produce biologically active compounds like B vitamins (niacin and folate for example), vitamin K, and conjugated linoleic acids, all powerful bioactive agents targeting regulation of various inflammatory and metabolic pathways in man. Moreover, both the physiological concentrations of these compounds and their biological activity change throughout life, driven both by diet and successional development of the gut microbiota, identifying diet:microbe interactions as an important extra-genomic epigenetic mediator capable of impacting on physiological processes linked to chronic disease risk and the ageing process itself. Recent studies indicate that processes within the gut play a critical role in the persistent low grade systemic inflammation common to many chronic human diseases associated with modern diet and life-style. Increased intestinal permeability leads to translocation of inflammatory molecules such as lipopolysaccharide, which then act as continuous triggers for unresolved systemic inflammation. This intestinal permeability and emergence of aberrant microbiota profiles is strongly influenced by diet, with high fat - low fiber diets (the modern or Western style diet) contributing to gut wall permeability. Conversely, ancestral or traditional dietary patterns high in fermentable fiber, prebiotics, fruit and vegetables (and indeed certain probiotic or fermentative microorganisms) support microbiome structure and function and improve gut barrier integrity (Figure 1).
A number of gut bacteria, including species of bifidobacteria and lactobacilli commonly used as probiotics, SCFA and the bile acid regulated nuclear receptor, FXR, have all been shown to control gut permeability via induction of tight junction proteins between epithelial cells. Similarly gut inflammation and oxidative damage play their part in gut “leakiness”, and are themselves impacted by both diet and the gut microbiome. Indeed, this diet induced intestinal damage and gut permeability, which is also characteristic of certain chronic disease states like obesity strongly mirrors the gut leakiness and chronic low grade systemic inflammation observed in the elderly, and at least in models of ageing, harbingers unresolved inflammation, metabolic derangement, diabetes and eventually death (Rena et al. 2012).
Of course the ancients knew this all along - “death sits in the bowel” Hippocrates c. 400 BC. However, we are now providing the mechanistic understanding of how the gut microbiota may constitute a lynch-pin upon which the destructive degenerative processes of aberrant metabolic and inflammatory pathway activation are held at bay until overwhelmed by advancing age or aberrant diet. When this occurs, or what chronic disease expresses itself, is of course determined by host genetic predisposition, but it appears that diet:microbiota interactions in the gut contribute significantly to the environmental pressure driving these metabolic and inflammatory disease processes. Diet is one disease risk factor we can modify, and understanding on the one hand, what dietary components contribute to disease risk, and on the other hand, those which reduce disease risk is critical if we are to reduce the burden of chronic non-communicable diseases. Adherence to the Mediterranean style diet has been proven to protect against these chronic non-communicable diseases and improve mental well-being (Bonaccio et al. 2013) and indeed, recent studies are showing that components of the Mediterranean diet may mediate, at least part of their protective effects, through the gut microbiome (Figure 1, Tuohy and Del Rio, 2014). This lecture will provide an insight into recent studies illustrating how diet:microbe interactions in the gut not only contribute to chronic disease risk, but also hold great potential of reducing the socioeconomic impact of these diseases through rational modulation of dietary patterns throughout life
The Microbiota of the human gastrointestinal tract: a molecular view
No full textThe human gut microbiota represents a complex collection of microorganisms, which contribute considerably to host health. They occupy different ecological niches and habitats within the gastrointestinal tract and vary both in compositional make up and metabolic output at different sites along the gut. In this chapter, we describe the microbial “geography” within the human gastrointestinal tract and discuss available methods for studying the gut microbiota at both taxonomic and metabolic levels. Tremendous advances have been made in
culture independent molecular microbiology over the past 20 years giving previously undreamt of insight into the architecture of the gut microbiota. Similarly, advances in “omics” technologies, especially metagenomics and metabolomics, are providing the tools necessary to give, for the first time, a real insight into both the gut
microbiota metabolic potential (encoded by the genes of microbiota metagenome) and the metabolic kinetic (comprising the flux of microbially derived metabolites) and how these then interact with host physiology
influencing health and disease ris
Does the gut microbiome have a role to play in the health effects of whole plant foods: evidence from in vitro and in vivo studies
No full textEpidemiological studies show that ingestion of whole plant foods, vegetables, fruit and whole grain cereals, is inversely related with chronic disease. Conversely, poor diet, typified by the modern Western style diet, rich in refined carbohydrates, red meat, processed foods and low in whole plant foods and fiber is associated with increased disease risk. Aberrant gut microbiota profiles define the intestinal microbiota in obesity, diabetes (both type 1 and type 2), intestinal cancer and autoimmune disease. Similarly, microbial metabolites of red meat derived choline and L-carnitine have been directly linked with CVD. Importantly, the gut microbiota too is critical for rendering some of the most important plant food molecular components, non-digestible carbohydrates and polyphenols, into biologically available and biological active intermediates. This raises the intriguing possibility that not only is gut microbiota whole plant food metabolism associated with protection from chronic disease but that we may be able modulate the gut microbiota and their activities using whole plant foods. Our ecological studies examining the gut microbiota of children growing up in rural Africa with those in urban Italy show that diet and dietary transition can dramatically impact on the gut microbiome. Similarly, we have shown that dietary intervention with certain whole plant foods can improve recognised biomarkers of metabolic disease and concomitantly modulate gut microbiota profiles. Here we discuss how whole plant foods may be employed to modulate the gut microbiome giving specific examples from both in vitro models systems and human studie
Diet : Microbe interactions - ecosystem support
No full textRecent metagenomic studies are confirming what pioneers in gut microbiology have long said, that diet:microbe interactions in the gut impact on human health and disease. The gut microbiota appear to regulate various physiological functions including host energy metabolism, immune homeostasis, and brain development and function. The gut microbiota produces a range of biologically active metabolites, not least, short chain fatty acids, small phenolic compounds derived from polyphenol metabolism, and, immunologically and neurologically active amino acid derivatives such as gamma-aminobutyric acid, serotonin and dopamine. Microbiota activities also control systemic tryptophan metabolism and peripheral concentrations of potentially harmful metabolites derived from choline and carnitine metabolism, notably the cardiotoxicant trimethylamine-N-oxide. The gut microbiota also determines the profile of bile acids returning to the liver through the enterohepatic circulation, important cell signalling molecules involved in various physiological functions, including host energy metabolism and immune function. Diet in large part regulates these important microbiota physiological services and dietary constituents, particularly the relative proportions of fermentable fiber and plant polyphenols on the one hand, and refined sugars, fat and animal protein, on the other, appear to critically determine the flux of either beneficial or potentially harmful metabolites from the gut. This presentation will discuss how diet regulates both the composition and metabolic output of the gut microbiota constituting, in effect, ecosystem support, not just for the gut microbiota, but for the greater human:microbe ecosystem as a whol
Gut-systemic inflammatory axis - “role of nutrition in fighting the modern plague of autoimmune and metabolic related diseases”
No full textThe incidence of autoimmune diseases has risen dramatically since the 1940’s with classical autoimmune diseases such as type 1 diabetes, celiac disease, inflammatory bowel disease, Multiple sclerosis, Amyotrophic lateral sclerosis (ALS), asthma, psoriasis and rheumatoid arthritis, now affecting about 5-10% of the global population depending on what diseases you include in the definition of AD’s. There is also a strong geographical distribution of these diseases, with increased prevalence in the richer areas of the world, or rather a strong socioeconomic component in the epidemiology of these diseases, with AD’s directly correlating with industrial development, urbanisation or Westernisation even in developing countries with historically low incidence of these diseases. AD’s are thought to derive from a combination of genetic predisposition and environment, or “bad genes and bad luck”. Diet is probably the most pervasive of environmental interactions with the human body, and diet too has changed dramatically since the 1940’s. The post-World War II diet which emerged in affluent countries in the 1950’s and became known as the Western-style diet, is typified by increased daily energy intake, high intake of refined carbohydrates especially sugars, high intake of fat, especially saturated fat, and animal protein and low intake of fresh fruit and vegetables, important sources of dietary fiber, polyphenols, minerals and vitamins. The Western diet too is typified by increased intake of highly processed foods, often energy dense but nutrient poor, leading to high intake of readily available energy sources and flavourings like sodium chloride and monosodium glutamate, but poor in minerals and vitamins as well as being low in fiber and phytochemicals. These biologically active compounds are emerging as important regulators of many mammalian physiological processes including those linked to immune tolerance and homeostasis, and are contributing to the recognised phenomenon of “nutrient malnutrition” alongside “energy over-nutrition”. Interestingly, AD’s are extremely rare in populations following traditional diets but this changes when indigenous peoples from rural areas following traditional lifestyles move to the cities and adopt Western-style lifestyles and diets.
The Western-style diet too has been linked to the increased prevalence of other diseases with strong immunological and autoimmune components, including allergies, food allergies and atopic dermatitis and obesity and the diseases of obesity (type 2 diabetes, non-alcoholic fatty liver disease, coronary vascular disease and certain cancers), and since in most affluent, Westernised communities obesity is reaching about 30% of the population, the health burden of autoimmunity is sky-rocketing.
Although not formally classed as autoimmune diseases, these common metabolic pathologies are characterised by persistent low grade systemic inflammation typified by elevated plasma CRP, IL-6, IL-1 and TNF-α, and are also associated with elevated blood levels of autoantibodies. Gut permeability to inflammatory bacterial lipopolysaccharide appears to be an important trigger for this low grade systemic inflammation, a processes directly impacted by the gut microbiota and their interaction with diet, especially fat and dietary fibers. In addition, certain members of the gut microbiota have been shown to induce mimics of human antigens and trigger autoantibodies responsible for aberrant immune responses to normal human proteins and hormones, an important consideration with the recent recognition of an “obese type” gut microbiome. Recently, metabolism of dietary phosphatidylcholine and L-carnitine, mainly provided by red meat and other animal products in the Western-style diet, has been shown to produce trimethylamine (TMA) which is further metabolised to trimethylamine-N-oxide (TMAO) by the liver and shown to play a direct role in CVD. TMAO modulates macrophage inflammatory status, reverse cholesterol metabolism, plasma bile acid concentrations and BA signalling through FXR. These CVD associated inflammatory and metabolic processes mediated by the gut microbiota were found to be induced by dietary red meat and down regulated in vegans. The adverse impact of the energy dense, nutrient poor Western-style diet on our gut microbiota and immune system, which have both been finely tuned and honed by high-fiber, high polyphenol traditional diets over the millennia, may therefore be an important contributor to the environmental stimuli which trigger these modern autoimmune and metabolic diseases of affluence.
A possible starting point when discussing the underlying mechanisms by which diets rich in whole plant foods or fermentable fibers can impact on immune function and tolerance may be the recent demonstration that butyrate, an important fermentation end product produced by the gut microbiota from fiber, controls human dendritic cell maturation, a key process in immune homeostasis since dendritic cells are considered the “gate keepers” of our immune system. SCFA has also been shown to play a role in regulating other immune parameters, including neutrophil and macrophage activity, and the gut microbiota has also recently been shown to produce other immuno active compounds such as conjugated linoleic acid (CLA) and gamma-aminobutyric acid (GABA) with have anti-inflammatory potential. Similarly, up-regulating microbial activities within the enterohepatic circulation of bile acids, through bile acid receptors (e.g. GRP5) and nuclear receptors (especially FXR) and in combination with immune signalling via tole-like receptors, is emerging as an important communication highway linking the gut microbiota:host immune metabolic axis intimately with the environmental risk factors of autoimmune and metabolic disease. In this presentation, I will discuss how diet, through its interaction with the human microbiome, both microorganisms themselves and their metabolic output, may play a role in immune homeostasis both within the gut and systemically, and could possibly provide novel therapeutic options to help in the fight against the modern plague of autoimmune and metabolic disease
Mode of delivery, route of delivery and diet all regulate infant microbiota and metabolome
No full textThe intestinal microbiome is now recognised as playing an important role in human health and disease, impacting on many host physiological processes from metabolism and immune homeostasis to brain development and even cognitive function. Importantly, many of these physiological processes appear to be affected by early life events. Maternal health during pregnancy, term of birth, mode of delivery (Spontaneous Vaginally Delivered or Caesarean-section), infant diet (breast feeding, infant formula feed, fortified infant formula) and exposure to microorganisms (both pathogenic and commensal) all impact on neonatal physiological development and later life health or disease risk. Many studies, using different microbiological approaches have characterised the successional development of the infant gut microbiota. Some have also correlated microbiota composition with concomitant changes in health status (e.g. incidence of infections) or physiological biomarkers. Studies in animals and using in vitro microbiota models have identified prebiotics capable of modulating the architecture of the infant gut microbiota and intervention studies in healthy infants have also confirmed that infant formula fortified with prebiotics can modulate the gut microbiota of formula fed infants towards that of breast-fed infants. In this presentation we will assess the potential of fructans (inulin and oligofructuse in particular) as prebiotic ingredients capable of modulating the composition of the infant gut microbiota. We will discuss evidence of safety, tolerability and impact on microbiota metabolic output. Finally, we will discuss the need for wider application of whole systems metabolic profiling or metabolomics to study the metabolic consequences of microbiota modulation, using a specific example data-set. In a collaborative study with University College Cork in Ireland, we have measured the metabolic implications of early life events in terms of urinary metabolite profiles using LC-MS based metabolomics in 199 breast fed infants. Mode of delivery and term v pre-term birth clearly impacted on urinary metabolite profiles, with 5000 statistically significant biomarkers separating infant groups. Remarkably, these shifts in metabolite profiles reflected closely differentiative clustering of faecal microbiota at the same time point, indicating that gut microbiota derived metabolites contribute significantly to the urinary metabolome in infants and more importantly, that changes within the intestinal microbiome brought on by early life events have clear and measurable consequences in terms of infant metabolism. These observations identify metabolomics as a powerfully informative tool for studying diet:microbiota interactions, especially in infants, and a technology likely to provide new mechanistic insight linking microbiota modulation with physiological response or health effects in babies
Food Bioactives: interactions with gut microbiota structure and function
No full textRecent metagenomic studies have highlighted significant associations between dysregulation of the intestinal microbiome and chronic disease risk in humans. Indeed, many diet and life-style associated diseases, obesity, type 2 diabetes, autoimmune diseases and certain cancers, all appear to possess characteristic profiles of gut bacteria and dysbiosys at the genetic level, with differences both in microbial diversity and relative abundance of important groups of gut bacteria compared to healthy individuals. However, clear links between aberrant microbiota composition and disease mechanisms in the host remain elusive. This presentation will focus on metabolic links between host and microbiome, metabolic links which appear to be altered in disease states and which in turn appear to be modifiable through dietary intervention. Interactions between specific dietary components, e.g. fermentable fibers/prebiotics, polyphenols and aromatic amino acids, appear to strongly influence both the composition and metabolic output of the gut microbiota and modify metabolites of known importance in physiological pathways regulating host metabolism and immune function. Similarly, high resolution MS based metabolomics is presenting a detailed picture of host:microbiome co-metabolism of many complex dietary components, providing novel biomarkers of intake and new putative therapeutic targets. Using data from model systems and human dietary interventions, the ability of host:microbiota co-metabolism to impact significantly on the risk of metabolic disease will be discussed using examples combining microbiome 16S rRNA sequence based profiling (metataxonomics) and biofluid targeted and untargeted MS based metabolomics. Using this combined “metataxonomic” and metabolomic approach, we have observed clear partitioning of microbiota metabolic output according to community structure at the taxonomic level, providing a useful tool linking microbiota structure with metabolic function
Toward microbial fermentation metabolites as markers for health benefits of prebiotics (and probiotics)
No full text- …
