A study by Ryan Newton and colleagues in mBio, the open access journal of the American Society for Microbiology, found that the bacterial composition of city sewage can almost precisely predict obesity rates in that city.
The researchers studied the microbial community of sewage from 71 US cities from 31 states using high-througput 165 rRNA gene sequencing technology.
Although on average only 15% of bacterial sequences in each sample represented bacteria known to occur in human stool, they were able to capture most (97%) of human fecal oligotypes.
Based on the distribution of three primary oligotypes representing different proportions of Bacteroidaceae, Prevotellaceae, or Lachnospiraceae/Ruminococcaceae, the researchers were able to predict whether samples came for cities with high or low prevalence of obesity with 81-89% accuracy.
No such relationship was found with non-fecal oligotypes, suggesting that this relationship was indeed due to the representation of human fecal bacteria in the sewage samples.
Obviously, it is very possible that the sewage bacterial composition reflects “lifestyles” associated with obesity rather than actual body weights, but the very fact that it was possible to identify important predictive differences in bacterial patterns between cities with varying obesity rates, together with the increasing recognition that gut bacteria may well play a role in obesity (and other metabolic diseases), is fascinating enough.
Should these findings be reproducible across other populations, I can only wonder whether sewage sampling may one day serve as a simple way to study changes in nutrition and obesity rates in whole populations.
Indeed, I can picture future public health scientists poring over sewage data to check if their public health policies to reduce obesity are in fact working.
In last week’s 2015 Lancet series on obesity, the majority of papers focus on policy interventions to address obesity. It suggests that a reframing of the obesity discussion, that avoids dichotomies (like nature vs. nurture debates) may provide a path forward – both in prevention and management.
The policy framework presented by Christina Roberto and colleagues in The Lancet, is based on the NOURISHING framework, proposed by the World Cancer Research Fund International to categorise and describe these actions.
Together, the actions in this framework address the food environment (e.g. food availability, taxation, restrictions on advertising, etc.), food systems (e.g. incentives and subsidies for production of healthier foods) and individual behaviour change (e.g through education and counselling).
This “food-centric” view of obesity is complemented by recognising that physical activity, much of which is dictated by the built environment and captivity of the population in largely sedentary jobs, also has a role to play.
On a positive note, the Christina and colleagues suggest that there may be reasons for careful optimism – apparently 89% of governments now report having units dedicated to the reduction of non-communicable diseases (including obesity), although the size and capacity of many of these units is unknown.
On the other hand, despite an increasing number of such efforts over the past decades, no country has yet reversed its epidemice (albeit there is a flattening of obesity growth rates in the lower BMI ranges in some developed countries – with continuing rise in more severe obesity).
Despite the potential role of government policies in reducing non-communicable diseases (including obesity) by “nudging” populations towards healthier diets and more physical activity, the authors also note that,
“…the reality is that many policy efforts have little support from voters and intended programme participants, and although the passage of policies is crucial, there is also a need to mobilise policy action from the bottom up.”
Indeed, there is growing list of examples, where government policies to promote healthy eating have had to be reversed due to lack of acceptance by the public or were simply circumvented by industry and consumers.
Nevertheless, there is no doubt that policies in some form or fashion may well be required to improve population health – just how intrusive, costly and effective such measures will prove to be remains to be seen.
All of this may change little for people who already have the problem. As the article explains,
“There are also important biological barriers to losing excess weight, once gained. Changes in brain chemistry, metabolism, and hunger and satiety hormones, which occur during attempts to lose weight, make it difficult to definitively lose weight. This can prompt a vicious cycle of failed dieting attempts, perpetuated by strong biological resistance to rapid weight loss, the regaining of weight, and feelings of personal failure at the inability to sustain a weight-loss goal. This sense of failure makes people more susceptible to promises of quick results and minimally regulated claims of weight loss products.”
Not discussed in the article is the emerging science that there may well be other important drivers of obesity active at a population level that go well beyond the food or activity environment – examples would include liberal use of antibiotics and disinfectants (especially in agriculture), decreased sleep (potentially addressable through later school start times and mandatory afternoon naps in childcare settings), increasing maternal age at pregnancy (addressable by better access to childcare), time pressures (e.g. policies to address time-killing commutes), etc.
Perhaps what is really needed is a reframing of obesity as a problem where healthy eating and physical activity are seen as only two of many potential areas where policies could be implemented to reduce non-communicable diseases (including obesity).
Some of these areas may well find much greater support among politicians and consumers.
In 2011, The Lancet dedicated a special issue to the topic of obesity – the general gist being that obesity is a world wide problem which will not be reversed without government leadership and will require a systems approach across multiple sectors. The Lancet also noted that current assumptions about the speed and sustainability of weight loss are wrong.
This week, The Lancet again dedicates itself to this topic with ten articles that explore both the prevention and management of obesity.
According to Christina Roberto, Assistant Professor of Social and Behavioural Sciences and Nutrition at the Harvard T H Chan School of Public Health and a key figure behind this new Lancet Series, “There has been limited and patchy progress on tackling obesity globally”.
Or, as Sabine Kleinert and Richard Horton, note in their accompanying commentary, “While some developed countries have seen an apparent slowing of the rise in obesity prevalence since 2006, no country has reported significant decreases for three decades.”
As Kleinert and Horton correctly point out, a huge part of this lack of progress may well be attributable to the increasingly polarised false and unhelpful dichotomies that divide both the experts and the public debate, thereby offering policy makers a perfect excuse for inaction.
These dichotomies include: individual blame versus an obesogenic society; obesity as a disease versus sequelae of unrestrained gluttony; obesity as a disability versus the new normal; lack of physical activity as a cause versus overconsumption of unhealthy food and beverages; prevention versus treatment; overnutrition versus undernutrition.
I have yet read to read all the articles in this series and will likely be discussing what I find in the coming posts but from what I can tell based on a first glance at the summaries, there appears to be much rehashing of appeals to governments to better control and police the food environments with some acknowledgement that healthcare systems may need to step up to the plate and do their job of providing treatments to people who already have the problem.
As much as I commend the authors and The Lancet for this monumental effort, I would be surprised if this new call to action delivers results that are any more compelling that those that followed the 2011 series.
I can only hope I am wrong.
Unfortunately, most people have rather simplistic views of genetics – either you have a gene for disease X and you get it, or you don’t have the gene for disease X and so you’re safe.
In reality, this is not at all how genetics works (with the few rare exceptions of single-gene disorders – and even there is not at all as straightforward as most people imagine).
In fact, whether or not a gene (or group of genes) actually results in a specific phenotype is highly dependent on the environment.
As a simple example: I could be genetically highly predisposed to salt-sensitivity (i.e. having a blood pressure increase on a high-salt diet) – but unless I am actually exposed to a high-salt diet, I can go my entire life without ever developing high blood pressure.
This is pretty much the case for all complex (and even some single-gene) disorders – it is only when you put the susceptible “disease gene(s)” in the wrong environment, that the gene does what it does. This is why most “nature vs. nurture” debates lead nowhere – it is virtually never one OR the other – it is mostly BOTH!
A good example of how changing environments may be important when studying the genetics of diseases is suggested in a new study by James Niel Rosenquist and colleagues, published in the PNAS.
The researchers examines the association between the FTO gene and BMI using longitudinal data from the Framingham Heart Study collected over 30 y from a geographically relatively localized sample in the US.
What they found was that the well-documented association between the rs993609 variant of the FTO (fat mass and obesity associated) gene and body mass index (BMI) varies substantially across birth cohorts, time period, and the lifecycle, with a apparently increasing impact of this gene for those born after 1942.
As the authors point out,
“Such cohort and period effects integrate many potential environmental factors, and this gene-by-environment analysis examines interactions with both time-varying contemporaneous and historical environmental influences.”
“These results suggest genetic influences on complex traits like obesity can vary over time, presumably because of global environmental changes that modify allelic penetrance.”
In other words, as the environment changes, certain genetic “phenotypes” may become more (or less) common.
It is however important to remember in this context that the term “environment” is rather broad and may include biological drivers that include changes in the epigenome, bacteriome or even virome, all of which will have substantially changed over time (and continue to change as we we speak).
On a more practical level, this is also why genetic testing for complex genetic diseases (and so-called “personalized” medicine) will likely be nothing more than a pipe dream and a money grab, at least for the foreseeable future.
Rosenquist JN, Lehrer SF, O’Malley AJ, Zaslavsky AM, Smoller JW, & Christakis NA (2015). Cohort of birth modifies the association between FTO genotype and BMI. Proceedings of the National Academy of Sciences of the United States of America, 112 (2), 354-9 PMID: 25548176
Last week, Edward Archer from the University of Alabama at Birmingham (UAB), published a paper in the Mayo Clinic Proceedings (to much media fanfare), suggesting that the primary driver of childhood obesity is the shifting of nutrient energy to fetal adipose tissue as a result of increased maternal energy availability paired with decreased maternal energy expenditure, resulting in fetal pancreatic b-cell and adipocyte hyperplasia – a theory, which Edwards labels the “maternal resource hypothesis”.
The primary process for these changes, as readers of these pages will have read before, is through epigenetic modification of DNA, which, together with other non-genetic modes of transmission including learned behaviours and environmental exposures (socioenvironmental evolution), leads to “phenotypic evolution”, which Edward describes as,
“…a unidirectional, progressive alteration in ontogeny that is propagated over multiple successive generations and may be quantified as the change over time in the population mean for the trait under examination (eg, height and obesity).”
Since the beginning of the 20th century, socioevironmental factors have significantly altered the energy balance equation for humans
“Socioenvironmental evolution has altered the evolution of human energy metabolism by inducing substantial decrements in EE imposed by daily life while improving both the quality and the quantity of nutrient-energy availability.”
“For example, as thermoneutral environments became ubiquitous, the energy cost of thermoregulation declined, and improved sanitation (eg, clean water and safer food) and vaccinations decreased the energy cost of supporting parasites (eg, fleas) and resisting pathogens (eg, communicable diseases and diarrheal infections).”
Over the past century, these developments have led to profound phenotypic changes including,
“progressive and cumulative increases in height, body stature and mass, birthweight, organ mass, head circumference, fat mass/adiposity as well as decreases in the age at which adolescents attain sexual maturity…”
Archer goes on to describe some of the many factors that may have changed in the past century, whereby, he singles out sedentariness as one of the key drivers of these developments (not surprising given Archer’s background in exercise science).
Thus, although one could perhaps make very similar arguments for any number of factor that may have changed in the past century to, in turn, affect insulin resistance and ultimately energy partitioning (change in diet, sleep deprivation, increasing maternal age, endocrine disruptors, antibiotic use, gut microbiota, medication use and many other factors I ca think of), Archer chooses to elevate sedentariness to being the main culprit.
While this may or may not be the full story, it does not change the thrust of the paper, which implies that we need to look for the key drivers of childhood obesity in the changes to the maternal-fetal (and early childhood) environment that have put us on this self-perpetuating unidirectional cycle of phenotypic evolution.
Ergo, the solution lies in focussing on the health behaviours (again, Archer emphasizes the role of physical activity) of moms.
While Archer largely focusses on maternal transmission, we should perhaps not forget that there is now some also evidence implicating a role for epigenetic modification and intergenerational transmission through paternal DNA – yes, dads are getting older and more sedentary too (not to mention fatter).
I do however agree with Edward, that this line of thinking may well have important implications for how we approach this epidemic.
“…the acknowledgment that obesity is the result of non-genetic evolutionary forces and not gluttony and sloth may help to alter the moralizing and demoralizing social and scientific discourse that pervades both public and clinical settings.”
“Future research may be most productive if funding is directed away from naive examinations of energy balance per se and redirected to investigations of interventions that alter the competitive strategies of various tissues.”
“From the standpoint of the clinician, accurate patient phenotyping (inclusive of family obstetric history and metabolic profiling) may allow the targeting of women most likely to be a part of populations that have evolved beyond the metabolic tipping point and therefore require significant preconception intervention.”
While none of this may be easier or more feasible than other current efforts, they may well point us in a different direction than conventional theories about what is driving childhood obesity.