A viral 'cause' of obesity?

I must thank Leah Hardy (@LeahFHardy) for bringing to my attention the paper by Qinglong Shang and colleagues [1] (open-access available here) reporting that: "Ad36 [Human adenovirus 36] infection is associated with an increased risk of obesity development."

Based on a meta-analysis of the available research literature examining whether Ad-36 - "a nonenveloped icosahedral virus comprised of double-stranded DNA and is one of 56 serotypes in 7 subgroups of human adenoviruses" - might be linked to obesity, researchers concluded that the weight of evidence from 11 studies did favour "an association between Ad36 infection and a significantly increased risk of obesity development, especially in children." Such findings can be added to other meta-analyses [2] that have also previously suggested that there may be more to see in this 'infectobesity' area [3].

I have to say that I was quite unaware of the links being made between Ad-36 and obesity prior to reading the Shang paper. I've previously tackled the idea that the obesity might have some important microbiological links (see here) before on this blog but never considered the possibility of a viral infection as showing involvement until now. Obviously one has to be a little guarded against making any sweeping statements that for example, Ad-36 is the primary cause of all obesity, because in all likelihood the issue is likely to be rather more complex than that. Appreciating that the old 'energy in, energy out' hypothesis is itself likely to be an over-simplification of why we are faced with growing rates of overweight and obesity, I'm sure that Ad-36 probably fits into a rather large jigsaw puzzle - somewhere. The requirement for a greater understanding of the hows and whys of any viral - obesity link is also strong alongside the idea that even if proved, any viral link should not absolve responsibility for eating and exercising right as part of maintaining a healthy weight.

Research such as that from Berger and colleagues [4] suggesting that "Ad36(+) may be associated with biomarkers implicated in inflammation but not with greater levels of fat mass" offers some cautionary data on why there may be quite a bit more research needed looking at Ad-36 and obesity. If one considers that inflammation seems to be part and parcel of obesity, the whole thing starts to get quite a bit more complicated.

Still, if science does start to get closer to the idea that Ad-36 (or other agents) might indeed heightened the risk of obesity and perhaps even suggest 'transferability' from person-to-person, this may open up new ways of tackling this issue [5] even with the prospect of immunising against infection-induced weight gain [6].

Music: Babies by Pulp.

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[1] Shang Q. et al. Serological data analyses show that adenovirus 36 infection is associated with obesity: a meta-analysis involving 5739 subjects. Obesity (Silver Spring). 2014 Mar;22(3):895-900.

[2] Yamada T. et al. Association of Adenovirus 36 Infection with Obesity and Metabolic Markers in Humans: A Meta-Analysis of Observational Studies. PLoS One. 2012; 7(7): e42031.

[3] Valiquette L. et al. A microbiological explanation for the obesity pandemic? Can J Infect Dis Med Microbiol. 2014 Nov-Dec;25(6):294-5.

[4] Berger PK. et al. Association of adenovirus 36 infection with adiposity and inflammatory-related markers in children. J Clin Endocrinol Metab. 2014 Sep;99(9):3240-6.

[5] Esposito S. et al. Adenovirus 36 infection and obesity. J Clin Virol. 2012 Oct;55(2):95-100.

[6] Na HN. & Nam JH. Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36. Int J Obes (Lond). 2014 Nov;38(11):1470-4.

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Shang Q, Wang H, Song Y, Wei L, Lavebratt C, Zhang F, & Gu H (2014). Serological data analyses show that adenovirus 36 infection is associated with obesity: a meta-analysis involving 5739 subjects. Obesity (Silver Spring, Md.), 22 (3), 895-900 PMID: 23804409

Microbes passing traits to host babies?

The paper by Clara Moon and colleagues [1] has garnered a lot of headlines with their findings suggesting that [mouse] mothers pass on bacteria to their [mouse] offspring. Their results reported in Nature, focused on a bacterium not unfamiliar to this blog, Sutterella (see here) and how, through the transmission of Sutterella via their poo(p), a specific trait might also be passed on. In this case, low levels of immunoglobulin A (IgA) (something else that has cropped up on this blog) were noted in offspring. The idea being that Sutterella might have an effect on IgA production and low IgA is a factor in quite a few conditions not least the inflammatory bowel diseases [2] and other autoimmune related conditions.

I have to say that I did a bit of double-take when reading this study and some of the accompanying media given the potential implications. "When we study mice, we have to account for the possibility that inherited bacteria and their genes could be influencing the trait we're trying to learn about," is a quote from one of the researchers involved in this work. Certainly this is the most pressing issue to come from the Moon study but the results are potentially much more profound than just where you house mice in a research setting. First though, I'd like to see some independent confirmation of these findings please.

Although there is quite a bit of hype around the microbiome these days, and particularly those trillions of beasties which reside in our gastrointestinal (GI) tract, there is something of a greater appreciation that their role(s) appears to extend well beyond just helping us digest food and producing the odd nutrient or two. My coverage of the 'poo transplant [potentially] made me obese' paper (see here) kinda hints at one possible alternative action for our gut bacteria or some other, related component of the gut. I'd also draw your attention back to the paper by Desbonnet and colleagues [3] talked about in this post, which brought the concept of 'psychobacteriomics' (my definition!) to the world and how gut bacteria might also impact on [mouse] social behaviour too.

Going back to the the Moon paper, I'm also drawn to the possible implications for a wide range of issues and diagnoses based on their findings. Genetics, more traditional structural genetics, based on investigations of how the structural differences of the genome might confer elevated/reduced risk of good or adverse health issues, is undergoing a bit of a revolution at the moment. Not only are we talking more about the epigenome (see the Nature special on this and a very informative video here) but as per some other comments from the paper authors, science is potentially thinking of an: "expanded model of heredity to produce a more complicated but also much more insightful picture of how human, bacterial and viral genes influence human health." This is all the more important when you consider how many bacterial genes there are vs. 'human' genes alongside the idea that just as viruses have a history of passing genes to humans (think HERVs) so bacteria may also be able to 'transfer' genes to us too. I wonder if the Moon findings might also account for those peculiar 'elevated levels of autoimmune conditions in the spouses of those with coeliac disease' findings [4] too?

Given that Sutterella is the starting point for this possible association, and with something of a potential role for this bacteria in some cases of autism [5] replicated even [6], one might entertain the idea that autism should perhaps figure in follow-up work in this area. I'm not suggesting that autism as a label (or labels) is somehow the product of Sutterella but as per the discussions linking Sutterella to potential bowel pathology in some cases of autism, whether the mechanism talked about by Moon and colleagues might also apply to humans too.

Then there is the tantalising idea of 'altering' the microbiome to alter specific traits...

So then, it missed out on an Oscar but the song is still awesome...

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[1] Moon C. et al. Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature. 2015 Feb 16.

[2] Ludvigsson JF. et al. Association between IgA deficiency & other autoimmune conditions: a population-based matched cohort study. J Clin Immunol. 2014 May;34(4):444-51.

[3] Desbonnet L. et al. Microbiota is essential for social development in the mouse. Mol Psychiatry. 2014 Feb;19(2):146-8.

[4] Emilsson L. et al. Autoimmune Disease in First-degree Relatives and Spouses of Individuals with Celiac Disease. Clin Gastroenterol Hepatol. 2015 Jan 30. pii: S1542-3565(15)00112-3.

[5] Williams BL. et al. Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. MBio. 2012 Jan 10;3(1).

[6] Wang L. et al. Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol Autism. 2013 Nov 4;4(1):42.

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Moon C, Baldridge MT, Wallace MA, Burnham CA, Virgin HW, & Stappenbeck TS (2015). Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature PMID: 25686606