Personal ViewA framework for identification of infections that contribute to human obesity
Introduction
Is it time to add a subtype of human obesity to the list of infectious diseases? To think of obesity as an infectious disease would be a departure from the traditionally held views about the causes of a disorder that has rapidly and inexplicably become a worldwide epidemic.1 Although the causes of obesity are multifactorial, behaviour that leads to overeating and underactivity is conventionally thought to be a major contributory factor. Prevention and treatment strategies that target such behaviour have not had much success, which has led to a search for additional risk factors for obesity. Several alleged risk factors, including certain infections, are under consideration.2 These factors could work alone or together to modulate susceptibility to weight gain or response to weight-loss efforts.
People who are overweight or obese have abnormal or excessive fat accumulation that presents a health risk. A measure of obesity is the body-mass index (BMI)—a person's bodyweight in kilograms divided by the square of their height in metres. A BMI of between 25 and 30 is viewed as overweight, whereas a score of 30 or more means a person is obese. The BMI cutoffs for obesity and overweight represent the points at which health risks substantially increase. The International Obesity Task Force cites obesity as a major risk factor for many serious disorders, such as diabetes, cardiovascular diseases, and cancer. Worldwide, a billion people are either overweight or obese.3 Although the exact reasons for the increase in obesity prevalence and its worldwide spread are unknown, if specific infections were to contribute to even a fraction of cases a great many people would be affected.
The mainstay of obesity treatment is advice on lifestyle changes—a non-specific approach. Despite the health benefits, compliance with lifestyle changes to achieve sustained improvements in diet or reductions in weight is challenging. Cause-specific approaches might be more effective than lifestyle advice in treatment of the obesity epidemic. Infectobesity, or obesity of infectious origin, might be treated with such specific approaches. Preventive strategies could include pathogen-specific vaccines and restricting the spread of infection, and treatment strategies could include antimicrobial therapies.
Evidence that specific infections might promote the development of obesity has steadily accumulated over the past 25 years. The first report4 on this topic showed an induction of obesity in mice experimentally infected with canine distemper virus. Since then, ten microbes have been causatively linked with obesity in animal models.5 These microbes include animal and human viruses, bacteria, parasites, and scrapie agents, and the models include insects, chickens, rodents, and non-human primates (table 1).
Although experimental infection in animals shows an adipogenic role for these microbes, unequivocal confirmation of their effects in people is awaited. Experimental infection of people to determine a cause and effect association between specific microbes and obesity is unethical. In the absence of direct experimental data, robust indirect evidence from several sources and approaches is needed, similar to how the link between smoking and lung cancer was established from epidemiological studies. Suggested approaches to investigate the adipogenic role of a potential candidate microbe include work in animals, cell culture, and human studies (panel). Work in animals could be used to determine and characterise the adipogenic effect of infection with a candidate microbe at physiological and molecular levels, whereas studies in people could determine the association between natural infection with a candidate microbe and obesity. In particular, longitudinal human studies that show changes in adiposity after natural infection with a candidate microbe would provide strong evidence of a cause and effect relation. The suggested approach (panel) has been used to assess the role of the human adenovirus Ad36 in human obesity.
Section snippets
Adipogenic adenoviruses
The adipogenic effect of adenoviruses has been studied in detail since my colleagues and I first reported the adipogenic role of the avian adenovirus SMAM-1 in chickens in India.13, 14 SMAM-1 is antigenically similar to chicken embryo lethal orphan virus (CELO), which is common among poultry in the USA.23 SMAM-1 increases adiposity in experimentally infected chickens and their naive cage-mates, suggesting horizontal transmission of obesity induced by the virus.13, 14 Paradoxically,
In animals
Ad36, a human adenovirus belonging to subgroup D, was the first human adipogenic virus reported. The virus was first isolated in Germany in a faecal sample from a girl with enteritis.27 This isolation is the only evidence that suggests a faecal–oral route of transmission for Ad36. A series of experiments showed that infection with Ad36 increases adiposity in several animal models including chickens, mice, rats, and marmosets.15, 16, 17, 18 Similar to SMAM-1, Ad36 infection significantly reduces
Do other microbes contribute to human obesity?
Many reports suggest that other microbes contribute to human obesity, including Chlamydia pneumoniae,47 Selenomonas noxia,48 Helicobacter pylori,49 and the gut microflora.50 Fernandez-Real and colleagues51 reported that the collective load of infection with herpes simplex viruses 1 or 2, enteroviruses, and C pneumoniae in a population correlates positively with fat mass. The investigators concluded that people “with increased fat mass could be more susceptible to developing multiple infections
Conclusion
Some infections possibly promote adiposity in human beings. The concept of infectobesity could have profound implications for prevention and treatment of this subtype of obesity and for public health. Although several microbes show an adipogenic effect in animal models, no such effect has been demonstrated unequivocally in humans. Ad36 shows a causative and correlative role in animal and human obesity, respectively, and a congruence between the phe notypic effects. Hence, it meets most of the
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