What Type Of Interaction Is A Bacteria That Breaks Down Food In The Intestines Of A Animal

Analysis Science and Politics of Nutrition

Office of the gut microbiota in nutrition and wellness

BMJ 2018; 361 doi: https://doi.org/x.1136/bmj.k2179 (Published thirteen June 2018) Cite this as: BMJ 2018;361:k2179

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Ana M Valdes , associate professor1 2,
Jens Walter , CAIP chair for nutrition, microbes, and gastrointestinal healththree,
Eran Segal , professor4,
Tim D Spector , professor5

^aneSchoolhouse of Medicine, Academy of Nottingham, City Hospital, Nottingham NG5 1PB, UK
^twoNIHR Nottingham Biomedical Enquiry Heart, Nottingham, UK
³Department of Agricultural, Food, and Nutritional Scientific discipline and Department of Biological Sciences, University of Alberta, Edmonton, Canada
⁴Department of Figurer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
⁵Section of Twin Enquiry and Genetic Epidemiology, King's College London, London, UK

Correspondence to: T D Spector tim.spector{at}kcl.ac.uk

Ana Grand Valdes and colleagues discuss strategies for modulating the gut microbiota through diet and probiotics

Microbiome refers to the commonage genomes of the micro-organisms in a particular environment, and microbiota is the community of micro-organisms themselves (box 1). Approximately 100 trillion micro-organisms (most of them bacteria, only also viruses, fungi, and protozoa) exist in the human gastrointestinal tract12—the microbiome is now all-time thought of as a virtual organ of the torso. The human genome consists of nigh 23 000 genes, whereas the microbiome encodes over three million genes producing thousands of metabolites, which replace many of the functions of the host,xiii consequently influencing the host's fitness, phenotype, and health.2

Box 1

Glossary

Microbiome—the collective genomes of the micro-organisms in a particular surroundings
Microbiota—the customs of micro-organisms themselves
Microbiota diversity—a measure of how many different species and, dependent on the diverseness indices, how evenly distributed they are in the community. Lower diversity is considered a marker of dysbiosis (microbial imbalance) in the gut and has been found in autoimmune diseases and obesity and cardiometabolic conditions, too as in elderly people
Operational taxonomic unit of measurement—a definition used to classify groups of closely related organisms. DNA sequences can be clustered according to their similarity to one another, and operational taxonomic units are defined based on the similarity threshold (ordinarily 97% similarity) set past the researcher
Colonocytes—epithelial cells of the colon
Germ-free animals—animals that have no micro-organisms living in or on them
Short chain fatty acids—fatty acids with ii to six carbon atoms that are produced by bacterial fermentation of dietary fibres

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Studying the gut microbiota

Twin studies have shown that, although there is a heritable component to gut microbiota, ecology factors related to diet, drugs, and anthropometric measures are larger determinants of microbiota composition.45

Gut microbes are key to many aspects of human health including immune,six metabolic5 and neurobehavioural traits (fig 1).78 Unlike levels of evidence support the role of gut microbiota in human health, from fauna models910 and human studies.4111213

Fig 1

Schematic representation of the role of the gut microbiota in health and disease giving some examples of inputs and outputs. CVD=cardiovascular disease; IPA=indolepropionic acrid; LPS=lipopolysaccharide; SCFA=brusk chain fatty acids; TMAO=trimethylamine North-oxide

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Fauna models can help identify gut microbes and mechanisms, though the degree to which findings interpret to humans is unknown. In humans, observational studies tin can show cantankerous-exclusive associations between microbes and wellness traits but are limited by the disability to measure out causal relations. The strongest level of evidence is obtained from interventional clinical studies—in particular, randomised controlled trials.

The composition of gut microbiota is normally quantified using DNA based methods, such as next generation sequencing of 16S ribosomal RNA genes or whole genome shotgun sequencing, which too let inference of microbiota functions.1415 Metabolic products of the microbiota are at present measurable in stool and serum using metabolomic methods.16

What does the gut microbiota exercise?

The gut microbiota provides essential capacities for the fermentation of not-digestible substrates like dietary fibres and endogenous intestinal mucus. This fermentation supports the growth of specialist microbes that produce brusque chain fat acids (SCFAs) and gases.17 The major SCFAs produced are acetate, propionate, and butyrate.

Butyrate is the main energy source for human colonocytes, can induce apoptosis of colon cancer cells, and can activate intestinal gluconeogenesis, having beneficial effects on glucose and energy homeostasis.18 Butyrate is essential for epithelial cells to swallow big amounts of oxygen through β oxidation, generating a state of hypoxia that maintains oxygen residual in the gut, preventing gut microbiota dysbiosis.19

Propionate is transferred to the liver, where it regulates gluconeogenesis and satiety signalling through interaction with the gut fat acrid receptors 18 Acetate—the well-nigh abundant SCFA and an essential metabolite for the growth of other bacteria—reaches the peripheral tissues where it is used in cholesterol metabolism and lipogenesis, and may play a function in fundamental appetite regulation.twenty Randomised controlled trials have shown that higher product of SCFAs correlates with lower diet-induced obesity21 and with reduced insulin resistance.22 Butyrate and propionate, just not acetate, seem to control gut hormones and reduce appetite and food intake in mice.21 Gut microbial enzymes contribute to bile acid metabolism, generating unconjugated and secondary bile acids that human activity as signalling molecules and metabolic regulators to influence important host pathways.23

Other specific products of the gut microbiota have been implicated directly in homo wellness outcomes. Examples include trimethylamine and indolepropionic acrid. The product of trimethylamine from dietary phosphatidylcholine and carnitine (from meat and dairy) depends on the gut microbiota and thus its amount in blood varies between people. Trimethylamine is oxidised in the liver to trimethylamine N-oxide, which is positively associated with an increased risk of atherosclerosis and major adverse cardiovascular events.24 Indolepropionic acrid is highly correlated with dietary fibre intake25 and has potent radical scavenging activity in vitro,26 which seems to reduce the chance of incidence of type 2 diabetes.25

The gut microbiota and obesity

The gut microbiota seems to play a function in the evolution and progression of obesity. Most studies of overweight and obese people show a dysbiosis characterised by a lower variety.^31-39 Germ-free mice that receive faecal microbes from obese humans proceeds more weight than mice that receive microbes from healthy weight humans.4 A large written report of UK twins constitute that the genus Christensenella was rare in overweight people and when given to germ free mice prevented weight gain.4 This microbe and others such equally Akkermansia correlate with lower visceral fat deposits.12 Although much of the confirmatory evidence comes from mouse models, long term weight proceeds (over x years) in humans correlates with low microbiota multifariousness, and this association is exacerbated by depression dietary fibre intake.28

Gut microbiota dysbiosis probably promotes diet induced obesity and metabolic complications past a multifariousness of mechanisms including immune dysregulation, altered energy regulation, altered gut hormone regulation, and proinflammatory mechanisms (such as lipopolysaccharide endotoxins crossing the gut barrier and entering the portal circulation2930; fig one).

Microbiota variety and health

Lower bacterial diversity has been reproducibly observed in people with inflammatory bowel disease,31 psoriatic arthritis,32 type one diabetes,33 atopic eczema,34 coeliac disease,35 obesity,36 blazon 2 diabetes,37 and arterial stiffness,38 than in salubrious controls. In Crohn's disease smokers have even lower gut microbiome variety.39 The association between reduced multifariousness and disease indicates that a species-rich gut ecosystem is more robust confronting ecology influences, equally functionally related microbes in an intact ecosystem tin compensate for the function of other missing species. Consequently, diversity seems to be a more often than not good indicator of a "healthy gut."4041 Just recent interventional studies indicate that major increases in dietary fibre can temporarily reduce variety, every bit the microbes that digest fibre get specifically enriched, leading to a change in composition and, through competitive interactions, reduced diversity.22

The functional role of the gut microbiome in humans has been shown using faecal microbiota transplantation.42 This procedure is effective in cases of severe drug refractory Clostridium difficile infection and is now routinely used for this purpose around the world.43 For other pathologies, faecal transplants are non yet clinical practice but have been explored.44 For instance, transplanting faeces from a lean healthy donor (allogeneic) to recipients with metabolic syndrome resulted in better insulin sensitivity, accompanied by altered microbiota limerick, than using autologous faeces.45

Furnishings of food and drugs on the gut microbiota

Specific foods and dietary patterns can all influence the abundance of unlike types of bacteria in the gut, which in turn tin affect health (tabular array ane).

Tabular array 1

Examples of foods, nutrients, and dietary patterns that influence human health linked to their effect on the gut microbiota

High-intensity sweeteners are commonly used every bit carbohydrate alternatives, beingness many times sweeter than sugar with minimal calories. Despite being "generally recognised as safety" by regulatory agencies, some animal studies accept shown that these sugar substitutes may have negative effects on the gut microbiota.46 Sucralose, aspartame, and saccharin have been shown to disrupt the balance and diversity of gut microbiota.46 Rats given sucralose for 12 weeks had significantly higher proportions of Bacteroides, Clostridia, and total aerobic bacteria in their guts and a significantly higher faecal pH than those without sucralose.47 Mice given sucralose for six months had an increase in the expression in the gut of bacterial pro-inflammatory genes and disrupted faecal metabolites.48

Food additives, such equally emulsifiers, which are ubiquitous in candy foods, have too been shown to affect the gut microbiota in animals.49 Mice fed relatively low concentrations of two ordinarily used emulsifiers—carboxymethylcellulose and polysorbate-fourscore—showed reduced microbial diversity compared with mice not fed with emulsifiers. Bacteroidales and Verrucomicrobia were decreased and inflammation promoting Proteobacteria associated with mucus was enriched .49

Other areas of concern include the side effects of pop restrictive diets on gut wellness. These include some strict vegan diets, raw food or "clean eating" diets, gluten-costless diets, and low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diets used to treat irritable bowel syndrome.

Vegans are viewed by some as healthier than omnivores. A study of 15 vegans and 16 ominvores institute hit differences in serum metabolites generated past the gut microbes just very pocket-sized differences in gut bacterial communities.50 A controlled feeding experiment of ten human omnivores randomised to receive either a high fat and low fibre diet or a low fat and high fibre for 10 days found very modest effects on gut microbiome composition and no difference in short chain fat acid production. Together these data support a greater role for diet influencing the bacterial derived metabolome than merely the short term bacterial community.50

Brute and in vitro studies indicate that gluten-free breadstuff reduces the microbiota dysbiosis seen in people with gluten sensitivity or coeliac disease.5152 Only most people who avoid gluten practise non have coeliac disease or proved intolerance, and a recent large observational study showed an increased risk of heart disease in gluten avoiders, potentially because of the reduced consumption of whole grains.53 One report showed that 21 healthy people had substantially unlike gut microbiota profiles later on four weeks on a gluten-free nutrition. Most people showed a lower affluence of several key beneficial microbe species.54

The low FODMAP nutrition has been shown in six randomised controlled trials to reduce symptoms of irritable bowel syndrome.5556 It is associated with a reduced proportion of Bifidobacterium in patients with irritable bowel syndrome, and responsiveness to this diet can exist predicted by faecal bacterial profiles.57 Low FODMAP diets pb to profound changes in the microbiota and metabolome, the elapsing and clinical relevance of which are equally yet unknown.5859

In addition to diet, medication is a key modulator of the gut microbiota composition. A large Dutch-Belgian population study showed that drugs (including osmotic laxatives, progesterone, TNF-α inhibitors and rupatadine) had the largest explanatory power on microbiota composition (10% of customs variation).13 Other studies have shown major effects of normally prescribed proton pump inhibitors on the microbial community, which could explicate higher rates of gastrointestinal infection in people taking these drugs.60 Antibiotics clearly accept an effect on gut microbes, and low doses are routinely given to livestock to increase their growth and weight. A large proportion of antibiotic use in many countries is for agriculture—particularly intensive farming of poultry and beef.61 Several observational human studies as well equally many rodent studies have pointed to an obesogenic effect of antibiotics in humans even in tiny doses found in food.61 But humans have very variable responses to antibiotics, and intervention studies have not shown consistent metabolic consequences.62 Pesticides and other chemicals are usually sprayed on foods, but, although levels tin be high, solid evidence for their harm on gut wellness and the effects of organic food is currently lacking.63

Insufficient clinical evidence exists to draw clear conclusions or recommendations for these or other dietary preferences based on gut microbiota. Merely future studies of nutrient additives, drugs, and the condom and efficacy of dietary modifications must take into account these advances and their result on the gut microbiota. This is becoming articulate in patients with cancer treated with immunochemotherapy, bone marrow recipients, and patients with autoimmune disorders on biologics, where pocket-size changes in their microbiota can cause major changes in their response.64 Moreover, brute experiments have shown the protective effects of phytoestrogens on breast cancer depend on the presence of gut microbes (such every bit Clostridium saccharogumia, Eggerthella lenta, Blautia producta, and Lactonifactor longoviformis) that can transform isoflavones into the bioactive compounds.65

Box two summarises our current knowledge on the interactions between gut microbiota, diet, and human health.

Box ii

Consensus and uncertainties

What we know

Probiotic supplementation has several beneficial furnishings on human health
The microbes in our gut influence and human energy metabolism222324252627282930313233343536373839404142434445
Diet and medication have a strong influence on gut microbiota composition
Microbiota composition influences response to chemotherapy and immunotherapy96
Microbiome limerick defines glucose response to foods and can be used to personalise diet94
Dietary fibre intake influences gut microbiota composition and is related to better health8687104

What we don't know

Are natural probiotics in food ameliorate than probiotic supplements? Should we take them preventively?
Tin can microbes influence nutrient choices and appetite?
Do low dose antibiotics in food affect homo wellness?
What is the consequence of pesticides in food on the gut microbiome? Is organic food better for the gut microbiota?
Should all new drugs and food chemicals be tested on the gut microbiota?

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Manipulating the gut microbiota through diet

Changes to the gut microbiota can occur within days of changing diet; remarkable differences were plant later African Americans and rural Africans switched diets for simply two weeks.66 Increased abundance of known butyrate producing leaner in the African Americans consuming a rural African diet caused butyrate production to increase 2.5 times and reduced synthesis of secondary bile acid.66 Another study comparing extreme shifts between constitute and animal poly peptide based diets showed these changes after just 5 days.67 But healthy microbiota are resilient to temporal changes by dietary interventions, meaning that homeostatic reactions restore the original community limerick, as recently shown in the instance of staff of life 68

Prebiotic foods and dietary fibre

Well-nigh national authorities define dietary fibre as edible sugar polymers with three or more monomeric units that are resistant to the endogenous digestive enzymes and thus are neither hydrolysed nor absorbed in the small intestine.69 A subset of dietary fibre sources is fermentable, which means that they serve as growth substrates for microbes in the distal bowel.70 Some not-digestible carbohydrates have been referred to as "prebiotics," which are defined as food components or ingredients that are not digestible by the human body but specifically or selectively nourish beneficial colonic micro-organisms (box 3).71 The prebiotic concept has been criticised for being poorly defined and unnecessarily narrow,72 and some scientists prefer the term "microbiota accessible carbohydrates,"xi which are essentially equivalent to fermentable dietary fibre in that they become available as growth substrates for gut microbes that possess the necessary enzymatic chapters to use them.70

Box three

What are prebiotics and probiotics?

Dietary amounts of protein, saturated and unsaturated fats, carbohydrates, and dietary fibre influence the abundance of different types of leaner in the gut. The microbiota can also exist modified by adding live micro-organisms to food or by periods of fasting.

Probiotics are alive leaner and yeasts that, when administrated in a viable form and in adequate amounts, are beneficial to human wellness. They are commonly added to yoghurts or taken as food supplements.
Prebiotics are divers as a substrate that is selectively used by host micro-organisms conferring a health benefit. Although all compounds considered prebiotics are microbiota accessible carbohydrates or fermentable dietary fibre, the opposite is not true. The prebiotic concept is an area of current debate70
Synbiotics contain a mixture of prebiotics and probiotics

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Consuming resistant starches has been shown to enrich specific bacterial groups (Bifidobacterium adolescentis, Ruminococcus bromii, and Eubacterium rectale) in some people.7475 The taxa enriched differ depending on the type of resistant starches and other dietary fibres,75 indicating that shifts are dependent on the carbohydrate's chemical structure and the microbes' enzymatic capacity to access them. Microbes need also to "adhere" to a substrate and tolerate the weather condition generated from fermentation (such every bit depression pH).76

The effect of microbiota attainable carbohydrates on the gastrointestinal microbiome composition tin can exist substantial, with specific species becoming enriched to found more than 30% of the faecal microbiota.7577 Thus, microbiota attainable carbohydrates provide a potential strategy to raise useful minority members of the microbiome. These changes merely terminal equally long as the carbohydrate is consumed, and they are highly individual, which provides a basis for personalised approaches. Many short term feeding trials with purified dietary fibres or even whole institute based diets either have no event on microbiota multifariousness or reduce it,22 merely tin can all the same have clinical benefits, potentially through metabolites such every bit small chain fatty acids.2267

Low fibre intake reduces production of small chain fat acids and shifts the gastrointestinal microbiota metabolism to use less favourable nutrients,78 leading to the production of potentially detrimental metabolites.7980 Disarming bear witness shows that the depression fibre Western diet degrades the colonic mucus barrier, causing microbiota encroachment, which results in pathogen susceptibility81and inflammation,82 providing a potential mechanism for the links of Western diet with chronic diseases. Two recent studies showed that the detrimental furnishings of loftier fat diets on penetrability of the mucus layer and metabolic functions could be prevented through dietary administration of inulin.8384 Overall, these findings, together with the part of butyrate in preventing oxygen induced gut microbiota dysbiosis,19 provide a stiff rational to enrich dietary fibre consumption to maintain intact mucosal barrier function in the gut.85

Considerable observational bear witness shows that fibre intake is benign for human health. 2 recent meta-analyses found clear links between dietary fibre and wellness benefits in a broad range of pathologies,8687 and a recent intervention written report found dietary fibres significantly reduced insulin resistance in patients with type 2 diabetes, with clear links to the shifts in the microbiota and beneficial metabolites (such as butyrate).45

Probiotic foods

Probiotics are live micro-organisms that, when administered in adequate amounts, confer a health do good on the host).88 Probiotics (mostly Bifidobacterium and Lactobacillus species) can exist included in a variety of products, including foods, dietary supplements, or drugs.

There are concerns that well-nigh microbe supplements are unable to establish themselves in the gut and fail to exert an consequence on the resident community.8990 But probiotics tin can affect health independently of the gut microbiota through direct effects on the host; for example, through allowed modulation or the production of bioactive compounds. The therapeutic effect of probiotic supplementation has been studied in a wide range of diseases.

We searched the Cochrane library of systematic reviews for "probiotic*", yielding 39 studies, and searched Medline for "systematic review" or "meta-assay" and "probiotic*", yielding 31 studies. We included information on systematic reviews of randomised controlled trials published in the past five years where the principal treatment was probiotics (non dietary supplements in general). Just studies that focused on comparisons of probiotics with a control grouping, that contained at to the lowest degree some moderate or high quality randomised controlled trials in the estimation of the authors of the systematic review, which resulted in a total of 22 systematic reviews (table 2). The assay of 313 trials and 46 826 participants showed substantial evidence for beneficial effects of probiotic supplementation in preventing diarrhoea, necrotising enterocolitis, acute upper respiratory tract infections, pulmonary exacerbations in children with cystic fibrosis, and eczema in children. Probiotics also seem to improve cardiometabolic parameters and reduced serum concentrationof C reactive protein in patients with type 2 diabetes. Chiefly, the studies were non homogeneous and were not necessarily matched for type or dose of probiotic supplementation nor length of intervention, which limits precise recommendations. Emerging areas of probiotic treatment include using newer microbes and combinations, combining probiotics and prebiotics (synbiotics),91 and personalised approaches based on profiles of the candidate microbes in inflammation, cancer, lipid metabolism, or obesity.92 Stable engraftment of a probiotic Bifidobacterium longum, for example, has been shown to depend on individualised features of the gut microbiota, providing a rationale for the personalisation of probiotic applications.93

Table 2

Summary of systematic reviews analysing the function of probiotics on clinical outcomes

Personalised nutrition and hereafter directions

Given the variation in the gut microbiota between people, the optimal diet of a person may demand to be tailored to their gut microbiota. Zeevi et al.94 obtained a multidimensional microbiota profile in 900 people and monitored nutrient intake, continuous blood glucose levels, and physical activity for 1 week. The researchers devised a machine learning algorithm to predict personalised glucose responses later on meals based on clinical and gut microbiome data and showed that it achieved significantly higher predictions than approaches such as sugar counting or glycaemic alphabetize scores. In a follow-up double blinded randomised crossover trial of 26 participants, personalised dietary interventions based on the algorithm successfully normalised blood glucose levels.94

A study on response to bread68 using a randomised crossover trial of one week long dietary interventions showed significant interpersonal variability in the glycaemic response to different bread types. The type of breadstuff that induced the lower glycaemic response in each person could be predicted based solely on microbiome data nerveless before the intervention.68 Much more research is needed to establish whether these kinds of personalised approaches are viable, sustainable, and have a positive effect on clinical outcomes.

Conclusions

We are entering an era where we tin increasingly modify wellness through food and measure the effects through our microbes or metabolites. Fibre is a key nutrient for a healthy microbiome and has been overlooked while debates take raged about carbohydrate and fat. The adverse effects on the microbiome of drugs and processed food ingredients can no longer be ignored. Given the current gaps in noesis, we demand clinical prove that tin be translated into clinical practice, ideally through randomised controlled studies that use consequent matrices of prebiotics or probiotics or faecal microbiota transplantation to appraise changes in gut microbiota limerick and in health outcomes.

Fundamental messages

Gut microbiota influences many areas of human health from innate immunity to ambition and energy metabolism
Targeting the gut microbiome, with probiotics or dietary fibre, benefits human being wellness and could potentially reduce obesity
Drugs, food ingredients, antibiotics, and pesticides could all take adverse effects on the gut microbiota
Microbiota should exist considered a central attribute in diet; the medical community should adapt their educational activity and public health messages
Fibre consumption is associated with beneficial effects in several contexts

Footnotes

Contributors and sources: AMV studies the molecular footing of ageing and complex disease and has recently investigated the office of gut microbiome composition on cardiometabolic disorders. JW has studied and reported widely on the microbial ecology of the gut microbiota, its role in host health, and how it can be modulated past diet. ES heads a multidisciplinary lab of computational biologists and experimental scientists focusing on diet, genetics, microbiome, and their effect on health and disease. His aim is to develop personalised diet and medicine. TDS leads the TwinsUK registry and British gut project as the head of a multidisciplinary team studying the genetic, dietary, and lifestyle determinants of human gut microbiome composition and its relationship to common diseases. All authors contributed, read, and approved the final version.
Competing interests: We have read and understood BMJ policy on competing interests and declare the following: AMV and TS are consultants to Zoe Global. JW has received research funding from industry sources involved in the manufacture and marketing of prebiotics and dietary fibres and is a co-owner of Synbiotics Solutions, a developer of synbiotic products. ES is a consultant of DayTwo Inc. AMV is funded past the NIHR Nottingham Biomedical Research Centre. JW is supported through the Campus Alberta Innovates programme and grants of the Canadian Institute of Health Enquiry (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), the JPI HDHL, and the Canadian Foundation for Innovation. ES is supported by the Crown Human Genome Middle; the Else Kroener Fresenius Foundation; Donald Fifty. Schwarz, Sherman Oaks, CA; Jack North Halpern, New York, NY; Leesa Steinberg, Canada; and grants funded by the European Research Council and the Israel Science Foundation. TwinsUK was funded by the Wellcome Trust; European Community'southward 7th Framework Plan (FP7/2007-2013). The study also receives back up from the National Institute for Health Research (NIHR) BioResource Clinical Enquiry Facility and Biomedical Enquiry Centre based at Guy's and St Thomas' NHS Foundation Trust and Male monarch'due south Higher London. TDS is an NIHR senior investigator.
Provenance and peer review: Commissioned; externally peer reviewed.
This commodity is one of a series commissioned by The BMJ. Open access fees for the series were funded by Swiss Re, which had no input on the commissioning or peer review of the manufactures. The BMJ thanks the series directorate, Nita Forouhi and Dariush Mozaffarian, for valuable advice and guiding selection of topics in the serial.

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