hmg-coa reductase The implications of the hygiene hypothesis

The implications of the hygiene hypothesis extend beyond allergy per se, as exemplified by the reduced risk of non-Hodgkin lymphoma for adults who were the first-born or only child in their family, and for those who developed allergy to pollen and perhaps to foods (Cozen et al., 2007; Grulich et al., 2005; Smedby et al., 2007). There are similar birth-order associations with young-adult Hodgkin lymphoma (Chang et al., 2004; Gutensohn et al., 1975; Mack et al., 2015; Westergaard et al., 1997); survivors of this malignancy had low hmg-coa reductase of the fecal microbiota (Cozen et al., 2013), an association compatible with the hygiene hypothesis but also with cancer and its treatment. Human microbiota studies of other conditions linked to the hygiene hypothesis are lacking. Our study had several important weaknesses. Some of the allergies were probably misclassified, because the questionnaire data were self-reported with no validation by a physician or an objective test. This would bias toward the null, by introducing noise into a true association between a condition and an exposure. Our cross-sectional design cannot distinguish whether the observed dysbiosis preceded or followed the development of allergies. The specimens represented only one time point, but this also would bias toward the null, reducing the chance to detect associations with time-varying fecal microbiome metrics. We did not investigate possible associations with seasonality, but rather adjusted for it. With this approach, we would not have identified transient changes as reported for pollen season in Japan (Odamaki et al., 2007). Avoidance of particular foods could alter the microbiota, but intake of these foods (peanuts, tree nuts, and shellfish) is probably too low to affect the microbiota of the general population. Antihistamines or other medications may have altered the allergic participants\' microbiota, although this has not been reported. We adjusted for reported use of probiotics and vitamins, based on the possibility that their use may have altered the microbiota. We excluded participants who used an antibiotic within one month, and adjusted analyses for earlier antibiotic use. In conclusion, American adults with allergies, especially but not exclusively to nuts and seasonal pollen, have lower richness and altered composition of their gut microbiota. This observation of an allergy-associated dysbiosis supports the hygiene hypothesis, but the origin of the dysbiosis is unknown. Also unknown is whether prevention or amelioration of the dysbiosis can modify allergy prevalence or severity (Costa et al., 2014; Singh et al., 2013). Clinical trials and other longitudinal studies Codon incorporate fecal microbiota characterization will be needed to address these questions.
Author contributions
Acknowledgments The authors are grateful to Drs. Howard Young and Emily Vogtmann for comments on the manuscript and especially to the participants. This project was supported by the Intramural Research Program of the National Cancer Institute (ZIA-CP-010214). As noted at http://microbio.me/americangut/FAQ.psp, the American Gut Project is a donation-supported academic effort and collaboration between the Earth Microbiome Project and the Human Food Project, all of which are primarily run out of the laboratory of Rob Knight at the University of California San Diego. The website notes that all data except information that needs to be kept confidential for privacy reasons is openly and freely released into public databases.
Introduction Despite major advances in vaccines, diagnostics, therapeutics and infection control measures, the “unfinished agenda” of infectious diseases remains a global threat. The Global Burden of Disease (GBD) Study 2013 reports that lower respiratory tract infections, diarrhoeal disease, HIV, and malaria were four of the top ten causes of disease burden globally, as measured by disability-adjusted life years (DALYs) (Murray et al., 2015). These four disease areas, plus tuberculosis (TB), comprised five of the top eleven causes of death worldwide in 2013 (GBD 2013 Mortality and Causes of Death Collaborators, 2014). Infectious diseases generate a large economic burden (Fonkwo, 2008) with antimicrobial resistance (AMR), the subject of a World Health Organization (WHO) action plan (World Health Organization, 2014) and a priority for the United Kingdom (UK) (Anon.,), European Commission (2011), and the US Centers for Disease Control and Prevention (CDC) (Anon.,), projected to cost an estimated $100 trillion by the year 2050 if unadressed (Anon., 2014).