Article

Historical Perspective on the Rise and Fall and Rise of Antibiotics and Human Weight Gain

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Abstract

In recent medical and popular literature, audiences have been asked to consider whether antibiotics have contributed to the rising obesity epidemic. Prominent magazines have stated that weight may be adversely affected by antibiotics that destroy existing microbiomes and replace them with less helpful ones. However, there is a long history of efforts to investigate the relationship between antibiotics and human weight gain. In the early 1950s, amid initial findings that low doses of antibiotics served as growth promoters in animal livestock, investigators explored the role of antibiotics as magic bullets for human malnutrition. Nevertheless, early enthusiasm was tempered by controlled studies showing that antibiotics did not serve as useful, nonspecific growth promoters for humans. In subsequent decades, against the backdrop of rising concern over antibiotic resistance, investigators studying the role of antibiotics in acute malnutrition have had to navigate a more complicated public health calculus. In a related historical stream, scientists since the 1910s have explored the role of the intestinal microflora in human health. By the 2000s, as increasing resources and more sophisticated tools were devoted to understanding the microbiome (a term coined in 2001), attention would turn to the role of antibiotics and the intestinal microflora in the rising obesity epidemic. Despite scientific and commercial enthusiasm, easy answers (whether about antibiotics or probiotics) have again given way to an appreciation for the complexity of human growth. History encourages caution about our hopes for simplistic answers for presumed "fat drugs" and slimming probiotics alike.

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... In the farming industry, antibiotic-laced feed is routinely used for maximizing animal growth (26), where greater weight gain in domestic ruminants is observed with earlier antibiotic exposure (27). Similarly, malnourished children have benefited from antibiotic treatments for the purpose of weight gain (28,29). Of great concern to public health authorities is the high burden of disease that results from overweight or obesity, along with concomitant rises in economic costs and greater strains on healthcare resources (30,31). ...
... This provides yet another reason that healthcare professionals should consider narrow-spectrum antibiotic use as an obesity reviews alternative to prescribing broad-spectrum antibiotics when possible (43)(44)(45)(46). Our results align with known differences in biological activity between broad-spectrum and narrowspectrum drugs (47) and their impact on gut microbial activity and metabolic efficiency (29,30). Korpela et al. (7) further demonstrated the destructive nature of broad-spectrum drugs and found incomplete recovery of the microbiota 2 years after macrolide exposure, whereas there was recovery within 12 months after penicillin exposure in children. ...
Article
Purpose Antibiotic use is associated with alteration of the gut microbiome and metabolic activity. As childhood obesity is a predisposing factor for adult obesity, addressing childhood risk factors to weight gain in early life is important. This review aims to investigate the association between infant antibiotic exposure (aged < 24 months) and childhood obesity or overweight. Methods Articles were retrieved from CINAHL, Cochrane CENTRAL, Embase and MEDLINE. Eligible articles investigated antibiotic use in exposed versus unexposed infants and measured childhood weight change. Data were synthesized narratively and meta‐analysed where possible. Results After title/abstract and full‐text screening, 17 articles representing 15 unique studies were included for narrative synthesis. We found a small association between antibiotic exposure in infancy (<24 months) and childhood overweight or obesity. The strongest associations were observed in boys versus girls and children exposed to multiple antibiotic courses or broad‐spectrum drugs. Meta‐analysis of 12 sets of results comparing the earliest age of exposure to any antibiotic with overweight or obesity at the latest age of outcome found a pooled odds ratio of 1.05 (95% confidence interval: 1.00–1.11). Conclusions Antibiotic exposure in infants, aged < 24 months, was associated with a small increase in odds of childhood overweight or obesity in some subgroups of children.
... In contrast, the drug regulatory authority in Pakistan refers to the codex standards for regulation of marketed probiotic products [58], without specifying any specific baselines or thresholds for their evaluation. The need for a comprehensive global harmonized framework of probiotic regulation has been debated elsewhere [59]. This study attempts to address the void that arises because of a lack of national-level surveillance and efficacy data o marketed probiotic supplements. ...
Article
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The local pharmacies and shops are brimming with various probiotic products that herald a range of health benefits. The poor quality of probiotic products in both dosage and species is symptomatic of this multi-billion-dollar market making it difficult for consumers to single out reliable ones. This study aims to fill the potential gap in the labeling accuracy of probiotic products intended for human consumption. We describe a combinatorial approach using classical culture-dependent technique to quantify and molecular techniques (16 s rRNA gene sequencing, multilocus sequence, and ribotyping) for strain recognition of the microbial contents. The full gamut of probiotic characteristics including acid, bile and lysozyme tolerances, adhesiveness, anti-pathogenicity, and degree of safeness were performed. Their capacity to endure gastro-intestinal (GIT) stresses and select drugs was assessed in vitro. Our results forced us to declare that the local probiotic market is essentially unregulated. Almost none of the probiotic products tested met the label claim. Some (11%) have no viable cells, and a quarter (27%) showing significant inter-batch variation. A lower microbial count was typical with undesirables constituting a quarter of the total (~ 27%). Half of the products contained antibiotic-resistant strains; the unregulated use of these probiotics carries the risk of spreading antibiotic resistance to gut pathobionts. Poor tolerance to gut conditions and mediocre functionalism make the case worse. The current regulatory systems do not take this discrepancy into account. We recommend an evidence-based regular market surveillance of marketed probiotics to ensure the authenticity of the claims and product effectiveness.
... (T. D. Luckey, 1959, 3 quoted in (Podolsky 2017)). ...
Chapter
In this chapter we review the development of hospital infection prevention and control (IPC) since the nineteenth century and its increasingly important role in reducing the spread of antibiotic resistance (ABR). Excessive rates of hospital-acquired infection (HAI) fell dramatically, towards the end of the nineteenth century, because of improved hygiene and surgical antisepsis, but treatment remained rudimentary until effective antibiotics became widely available in the mid-twentieth century. While antibiotics had profound clinical benefits, their widespread appropriate and inappropriate use in humans and animals inevitably led to the emergence of antibiotic resistance (ABR). Within 50 years, this could no longer be offset by a reliable supply of new drugs, which slowed to a trickle in the 1980s. In hospitals, particularly, high rates of (often unnecessary) antibiotic use and ABR are exacerbated by person-to-person transmission of multi-drug resistant organisms (MDRO), which have, so far, largely resisted the introduction of antimicrobial stewardship (AMS) programs and repeated campaigns to improve infection prevention and control (IPC). Despite clear evidence of efficacy in research settings, both AMS and IPC programs are often ineffective, in practice, because of, inter alia, insufficient resourcing, poor implementation, lack of ongoing evaluation and failure to consult frontline staff. In this chapter we review reasons for the relatively low priority given to preventive programs despite the ethical obligation of healthcare organisations to protect current and future patients from preventable harm. The imminent threat of untreatable infections may provide an impetus for a shared organisational and professional commitment to promoting the cultural and behavioural changes needed to successfully reduce the burdens of ABR and drug-resistant HAIs.
... Recent studies have found that early use of antibiotics increases the risk of obesity in humans [32,33], and the prevalence of antibiotic use might also be one of the reasons for the surge of obesity in patients. Roux-en-Y gastric bypass (RYGB) surgery is considered as the treatment strategy for patients with BMI ≥ 28 or BMI ≥ 25 with other obesityrelated diseases. ...
Article
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There are trillions and trillions of microorganisms in the human gut, and these microorganisms and their metabolites are closely related to human health. Recent studies have found that the abundance of Akkermansia muciniphila is decreased in many diseases. Supplementation of A. muciniphila is used to treat many diseases, suggesting it as a probiotic. Herbal medicines are considered as valuable asset of traditional Chinese medicine. Recent studies have revealed traditional Chinese medicine as a potential prebiotic agent for the treatment of many diseases. Hence, in this review, we aimed to provide a plausible mechanistic basis for the interactions between herbal medicines and A. muciniphila, and therapeutic benefits on this interaction in various illnesses.
... In this study, alcohol and antibiotic exposure and disease status were all associated with specific flora but had no effect at 6 and 12 months. Antibiotic use can lead to imbalances in intestinal flora and reduced diversity [34] , and diarrhea is associated with the abundance of Blautia [35] . In our study, treatment with antibiotics, infectious diseases, and diet appeared to cause the greatest differences in microbiota in children aged 24 months. ...
Preprint
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(1) Background: The colonization characteristics of infant gut microbiota are influenced by many factors at various stages, but few studies have explored the longitudinal effects of environmental tobacco exposure and quantitative weaning time on young children’ intestinal flora. The purpose of this study was to characterize the evolution of intestinal microflora in young children aged 0-2 years and the longitudinal effects of environmental tobacco exposure and weaning time on young children aged 6, 12, and 24 months. (2) Methods: A total of 37 maternal and children pairs were included in a tertiary general hospital in China and followed up for 2 years. General demographic information was collected on mothers (after delivery, 6 months, 12 months) and young children (6 months, 12 months, 24 months), including frequency of exposure and time of weaning, through self-made questionnaires. Fecal samples were collected from mothers in the third trimester of pregnancy and infants at 6, 12 and 24 months, and analyze the microbiota results using the V3-V4 gene sequence of 16S rRNA. (3) Results: the diversity of intestinal microflora in young children was the highest at 24 months and most similar to that in mothers. Weaning time was positively correlated with Lactobacillus in the intestines of infants aged 0 to 12 months. The diversity of microbiota exposed to environmental tobacco smoke at 6 months was lower than that of the non-exposed group, and the higher the exposure at 6-12 months, the lower the abundance of Blautia. (4) Conclusion: The gut microbiota of young children becomes more mature and complicated with age. The extension of complete weaning time to about 12 months is conducive to the colonization of beneficial bacteria. And the long-term exposure of children and the environment of tobacco smoke will affect the dysbiosis of gut microbiota.
... Whether STAT also causes weight gain in humans is unclear. Trials conducted between the 1950s and 1970s sought to determine whether antibiotic supplementation could be used to treat human malnutrition; however, the trials were halted because of concerns about selecting for antibiotic-resistant bacteria [18]. By 2005, the alarming global rise in obesity brought attention back to STAT, now as a possible cause of excessive weight gain due to unintended exposures [19]. ...
Article
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The high-fat, high-calorie diets of westernized cultures contribute to the global obesity epidemic, and early life exposure to antibiotics may potentiate those dietary effects. Previous experiments with mice had shown that sub-therapeutic antibiotic treatment (STAT)—even restricted to early life—affected the gut microbiota, altered host metabolism, and increased adiposity throughout the lifetime of the animals. Here we carried out a large-scale cohousing experiment to investigate whether cohousing STAT and untreated (Control) mice would transfer the STAT-perturbed microbiota and transmit its impact on weight. We exposed pregnant dams and their young offspring to either low-dose penicillin (STAT) or water (Control) until weaning, and then followed the offspring as they grew and endured a switch from normal to high-fat diet at week 17 of life. Cohousing, which started at week 4, rapidly approximated the microbiota within cages, lowering the weight of STAT mice relative to non-cohoused mice. The effect, however, varied between cages, and was restricted to the first 16 weeks when diet consisted of normal chow. Once mice switched to high-fat diet, the microbiota α- and β-diversity expanded and the effect of cohousing faded: STAT mice, again, were heavier than control mice independently of cohousing. Metabolomics revealed serum metabolites associated with STAT exposure, but no significant differences were detected in glucose or insulin tolerance. Our results show that cohousing can partly ameliorate the impact of STAT on the gut microbiota but not prevent increased weight with high-fat diet. These observations have implications for microbiota therapies aimed to resolve the collateral damage of antibiotics and their load on human obesity.
... While the susceptibility to infection was not significantly altered by antibiotic treatment (likely due to the fact that viral infections accounted for the majority of disease cases), a significant weight gain was noted in subjects receiving antibiotics compared to non-treated controls [44]. Around the same time, large-scale antibiotic use was introduced to enhance productivity in livestock, based on the observation that antibiotic treatment in the drinking water greatly increased the weight gain rate at constant food intake [45]. Thus, the link between the commensal microbiome and metabolism has already found widespread application in mammals, a practice that has only recently been reduced due to concerns about antibiotic resistance development [46]. ...
Article
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The last decade of research has witnessed a tremendous upsurge in our understanding of the intestinal microbiome and its role in a large range of human diseases, which has incited hopes for a rapid clinical utilization of the new insights for the development of microbiome-based therapies. Nonetheless, only a single microbiome-targeted therapy has so far found its way into clinical routine: fecal microbiota transplantation for patients suffering from recurrent Clostridium difficile infections. Herein, we discuss the current hopes, advances, challenges, and obstacles for translating basic microbiome research into therapeutic applications for a larger number of diseases and provide an outline of how such clinical applications might emerge.
... In an article purporting to set the record straight on microbiome terminology, it is even claimed that the term microbiota was defined for the first time by Lederberg in 2001 [6]. Remarkably, a 'History of Medicine' article in a recent Annals of Internal Medicine issue makes this same claim that Lederberg coined the term in 2001 [7]. ...
Article
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Contemporary science writing suffers from errors in quotations and misattributions. Given the importance of the microbiome to virtually every branch of science and medicine, its early origins and historical references are vital. Regardless of technological applications - culture technique or next-generation metagenomics - accurate referencing is essential to the scientific pursuit of truth. Despite claims and inferences to the contrary, the rich history of the study of microbiota and the microbiome didn’t begin in 2001; many lessons can be learned by closely examining the history of the gut-brain-microbiota connection, including the undervalued role of early pioneers in this field.
... Evidence from mice has shown that early exposure to antibiotics had altered their gut microbiota, increased fat mass, and negatively modulated hepatic metabolism and associated hormones, which predisposed them toward adiposity (Cho et al., 2012;Cox et al., 2014). The effect of early administration of antibiotics on human adiposity has also been seriously reviewed over the past few years (Mueller et al., 2014;Turta and Rautava, 2016;Podolsky, 2017) and there is growing consensus that their increased use maybe a reason for the obesity explosion we are witnessing today. ...
Article
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In the present world scenario, obesity has almost attained the level of a pandemic and is progressing at a rapid rate. This disease is the mother of all other metabolic disorders, which apart from placing an added financial burden on the concerned patient also has a negative impact on his/her well-being and health in the society. Among the various plausible factors for the development of obesity, the role of gut microbiota is very crucial. In general, the gut of an individual is inhabited by trillions of microbes that play a significant role in host energy homeostasis by their symbiotic interactions. Dysbiosis in gut microbiota causes disequilibrium in energy homeostasis that ultimately leads to obesity. Numerous mechanisms have been reported by which gut microbiota induces obesity in experimental models. However, which microbial community is directly linked to obesity is still unknown due to the complex nature of gut microbiota. Prebiotics and probiotics are the safer and effective dietary substances available, which can therapeutically alter the gut microbiota of the host. In this review, an effort was made to discuss the current mechanisms through which gut microbiota interacts with host energy metabolism in the context of obesity. Further, the therapeutic approaches (prebiotics/probiotics) that helped in positively altering the gut microbiota were discussed by taking experimental evidence from animal and human studies. In the closing statement, the challenges and future tasks within the field were discussed.
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There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an ‘implementation gap’. At a policy level, the design of internationally salient solutions that are able to address AMR’s interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise ‘good’ antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scales.
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To the Editor: Isanaka and colleagues (Feb. 4 issue)(1) report the results of a double-blind, placebo-controlled trial that showed no benefit from the routine use of amoxicillin in a cohort of children with uncomplicated severe malnutrition in Niger. The authors conclude that amoxicillin may not have a place in the empirical management of uncomplicated severe malnutrition in developing countries. We strongly support the view that antibacterial chemotherapy is not a magic bullet, and we wish to highlight the potential unintended consequences of the mass use of antibacterial agents in this context, including the potential for drug resistance. With the World . . .
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Childhood undernutrition is a major global health challenge. Although current therapeutic approaches have reduced mortality in individuals with severe disease, they have had limited efficacy in ameliorating long-term sequelae, notably stunting, immune dysfunction, and neurocognitive deficits. Recent work is providing insights about the role of impaired development of the human gut microbiota in disease pathogenesis, leading to new concepts for treatment and prevention. These findings raise intriguing basic questions about the mechanisms that direct normal gut microbial community assembly and functional maturation. Designing and implementing new microbiota-directed therapeutics for undernutrition highlights the need to simultaneously consider a variety of features of human biology as well as broader societal issues.
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Importance: Early-life antibiotic exposure has been associated with increased adiposity in animal models, mediated through the gut microbiome. Infant antibiotic exposure is common and often inappropriate. Studies of the association between infant antibiotics and childhood weight gain have reported inconsistent results. Objective: To assess the association between early-life antibiotic exposure and childhood weight gain. Design and setting: Retrospective, longitudinal study of singleton births and matched longitudinal study of twin pairs conducted in a network of 30 pediatric primary care practices serving more than 200,000 children of diverse racial and socioeconomic backgrounds across Pennsylvania, New Jersey, and Delaware. Participants: Children born between November 1, 2001, and December 31, 2011, at 35 weeks' gestational age or older, with birth weight of 2000 g or more and in the fifth percentile or higher for gestational age, and who had a preventive health visit within 14 days of life and at least 2 additional visits in the first year of life. Children with complex chronic conditions and those who received long-term antibiotics or multiple systemic corticosteroid prescriptions were excluded. We included 38,522 singleton children and 92 twins (46 matched pairs) discordant in antibiotic exposure. Final date of follow-up was December 31, 2012. Exposure: Systemic antibiotic use in the first 6 months of life. Main outcomes and measures: Weight, measured at preventive health visits from age 6 months through 7 years. Results: Of 38,522 singleton children (50% female; mean birth weight, 3.4 kg), 5287 (14%) were exposed to antibiotics during the first 6 months of life (at a mean age of 4.3 months). Antibiotic exposure was not significantly associated with rate of weight change (0.7%; 95% CI, -0.1% to 1.5%; P = .07, equivalent to approximately 0.05 kg; 95% CI, -0.004 to 0.11 kg of added weight gain between age 2 years and 5 years). Among 92 twins (38% female; mean birth weight, 2.8 kg), the 46 twins who were exposed to antibiotics during the first 6 months of life received them at a mean age of 4.5 months. Antibiotic exposure was not significantly associated with a weight difference (-0.09 kg; 95% CI, -0.26 to 0.08 kg; P = .30). Conclusions and relevance: Exposure to antibiotics within the first 6 months of life compared with no exposure was not associated with a statistically significant difference in weight gain through age 7 years. There are many reasons to limit antibiotic exposure in young, healthy children, but weight gain is likely not one of them.
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Background & aims: Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. Methods: We performed a retrospective cohort study of 21,714 children in The Health Improvement Network -a population-representative dataset of more than 10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. Results: In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR]=1.21; 95% confidence interval [CI], 1.07-1.38). Odds ratios increased with repeated exposures: for 1-2 prescriptions, OR=1.07 (95% CI, 0.91-1.23); for 3-5 prescriptions, OR=1.41 (95% CI, 1.20-1.65); for 6 or more prescriptions, OR=1.47 (95% CI, 1.19-1.82). Antifungal agents were not associated with obesity (OR=0.81; 95% CI, 0.59-1.11). Conclusions: Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity.
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Background/Objectives Antibiotics are commonly prescribed for children. Use of antibiotics early in life has been linked to weight gain but there are no large-scale, population-based, longitudinal studies of the full age range among mainly healthy children.Subjects/Methods We used electronic health record data on 163 820 children aged 3-18 years and mixed effects linear regression to model associations of antibiotic orders with growth curve trajectories of annual body mass index (BMI) controlling for confounders. Models evaluated three kinds of antibiotic associations - reversible (time-varying indicator for an order in year before each BMI), persistent (time-varying cumulative orders up to BMIj), and progressive (cumulative orders up to prior BMI [BMIj-1])-and whether these varied by age.ResultsAmong 142 824 children under care in the prior year, a reversible association was observed and this short-term BMI gain was modified by age (P<0.001); effect size peaked in mid-teen years. A persistent association was observed and this association was stronger with increasing age (P<0.001). The addition of the progressive association among children with at least three BMIs (n=79 752) revealed that higher cumulative orders were associated with progressive weight gain; this did not vary by age. Among children with an antibiotic order in the prior year and at least seven lifetime orders, antibiotics (all classes combined) were associated with an average weight gain of approximately 1.4 kg at age 15 years. When antibiotic classes were evaluated separately, the largest weight gain at 15 years was associated with macrolide use.Conclusions We found evidence of reversible, persistent, and progressive effects of antibiotic use on BMI trajectories, with different effects by age, among mainly healthy children. The results suggest that antibiotic use may influence weight gain throughout childhood and not just during the earliest years as has been the primary focus of most prior studies.International Journal of Obesity accepted article preview online, 21 October 2015. doi:10.1038/ijo.2015.218.
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Objective: The objective was to determine the effects of the probiotic, VSL#3, on body and fat mass, insulin sensitivity, and skeletal muscle substrate oxidation following 4 weeks of a high-fat diet. Methods: Twenty non-obese males (18-30 years) participated in the study. Following a 2-week eucaloric control diet, participants underwent dual X-ray absorptiometry to determine body composition, an intravenous glucose tolerance test to determine insulin sensitivity, and a skeletal muscle biopsy for measurement of in vitro substrate oxidation. Subsequently, participants were randomized to receive either VSL#3 or placebo daily during 4 weeks of consuming a High-fat (55% fat), hypercaloric diet (+1,000 kcal day(-1) ). Participants repeated all measurements following the intervention. Results: Body mass (1.42 ± 0.42 kg vs. 2.30 ± 0.28 kg) and fat mass (0.63 ± 0.09 kg vs. 1.29 ± 0.27 kg) increased less following the High-fat diet in the VSL#3 group compared with placebo. However, there were no significant changes in insulin sensitivity or in vitro skeletal muscle pyruvate and fat oxidation with the High-fat diet or VSL#3. Conclusions: VSL#3 supplementation appears to have provided some protection from body mass gain and fat accumulation in healthy young men consuming a High-fat and high-energy diet.
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Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. The primary outcomes were the rate of nutritional recovery and the mortality rate. A total of 2767 children with severe acute malnutrition were enrolled. In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64). Among children who recovered, the rate of weight gain was increased among those who received antibiotics. No interaction between type of severe acute malnutrition and intervention group was observed for either the rate of nutritional recovery or the mortality rate. The addition of antibiotics to therapeutic regimens for uncomplicated severe acute malnutrition was associated with a significant improvement in recovery and mortality rates. (Funded by the Hickey Family Foundation and others; ClinicalTrials.gov number, NCT01000298.).
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The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.
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The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers.
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Bulletin of the History of Medicine 72.1 (1998) 1-27 Alfred North Whitehead To what extent does philosophy influence medicine? The division between practical scientists and pondering philosophers is herein examined by focusing upon the origin and fate of Elie Metchnikoff's Bacillus bulgaricus therapy in the earliest decades of this century. Metchnikoff helped drive the rise of the yogurt industry through his proposal to transform the toxic flora of the large intestine into a host-friendly colony of B. bulgaricus. This therapy, at first intended as a preventive against the infirmities of old age, was presented in the context of the famous scientist's conception of the living organism as intrinsically disharmonious -- a conception diametrically opposed in orientation to the predominating late-nineteenth-century conceptions of harmony and balance. However, by the time Metchnikoff's therapy was assimilated by the English-speaking world, its philosophical origins had been forgotten and its use confined to the alleviation of specific intestinal disorders. In this article I will first trace the course of Metchnikoff's therapy through three stages: its incipience, the rejection of its underlying theoretical foundation in England in the first decade of the century, and the subsequent development of the therapy in the United States from the 1920s to the 1930s. Then, having explored the vagaries of Metchnikoff's famous therapy, I will trace the lesser-known fate of its theoretical foundations -- from their initial rejection, to their ultimate infiltration into American and British conceptions of health. My intent is to demonstrate that the differential rates of diffusion of Metchnikoff's novel therapy and theory into such cultures actually depended not only upon the therapy's potential efficacy, but also upon the differences between the underlying philosophy of the theory and the philosophical expectations of its recipients. Elie Metchnikoff was born in the Kharkov province of Russia in 1845. He was a volatile, neurotic, yet brilliant child -- traits that would persist throughout his scientific career. By the 1860s, he had completed his formal studies in embryology. The antiprogressivism characterizing his view of embryology, as this article will show, led him to an understanding of the relationship between ontogeny and phylogeny that differed in important ways from the relationship propounded by Ernst Haeckel's recapitulationist program. Metchnikoff most famously extended this antiprogressivism to his explanation of the process of inflammation: in 1883, through his experimental placing of thorns in starfish larvae, he first described the "phagocyte" as the amoeboid mediator of cellular immunity. Moving to the Pasteur Institute in 1888, Metchnikoff vociferously defended the importance of the role played by cellular immunity until his death in 1916, earning himself the Nobel Prize in 1908. But it is to his more popular exploits that this article now turns. Metchnikoff's original desire to transform the human intestinal flora was presented to the public in the first decade of this century as the result of a complex chain of ideas stemming from a unique underlying conception of health and pathology. Most late-nineteenth-century conceptions of the individual postulated health as a condition of given harmony, and pathology as a temporary deviation from such a healthy underlying state. Metchnikoff, however, as Alfred Tauber and Leon Chernyak have emphasized, reversed this conception: according to him, "the organism was intrinsically disharmonious and its biology was based on the endeavor of integrating the disharmonious elements by active processes." This reversal derived from a reinterpretation of ontogeny and phylogeny in large part stemming from Metchnikoff's own particular reading of Darwinism. At the level of ontogeny, he proposed a type of intraorganismic Darwinism, explaining that "embryological development proceeds with cell lineages that are potentially in competition. The organism cannot be viewed as growing as a harmonious whole. . . ." The growing organism required active "harmonizers," and this task was relegated to the phagocytes, whose function he had first described in 1883. The phagocytes not only...
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To investigate whether delivery mode (vaginal versus by caesarean section), maternal pre-pregnancy body mass index (BMI) and early exposure to antibiotics (<6 months of age) influence child's risk of overweight at age 7 years, hence supporting the hypotheses that environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight. Longitudinal, prospective study with measure of exposures in infancy and follow-up at age 7 years. A total of 28 354 mother-child dyads from the Danish National Birth Cohort, with information on maternal pre-pregnancy BMI, delivery mode and antibiotic administration in infancy, were assessed. Logistic regression analyses were performed with childhood height and weight at the 7-year follow-up as outcome measures. Delivery mode was not significantly associated with childhood overweight (odds ratio (OR):1.18, 95% confidence interval (CI): 0.95-1.47). Antibiotics during the first 6 months of life led to increased risk of overweight among children of normal weight mothers (OR: 1.54, 95% CI: 1.09-2.17) and a decreased risk of overweight among children of overweight mothers (OR: 0.54, 95% CI: 0.30-0.98). The same tendency was observed among children of obese mothers (OR: 0.85, 95% CI: 0.41-1.76). The present cohort study revealed that a combination of early exposures, including delivery mode, maternal pre-pregnancy BMI and antibiotics in infancy, influences the risk of overweight in later childhood. This effect may potentially be explained by an impact on establishment and diversity of the microbiota.
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Nevin Scrimshaw was the founding Director of the Institute of Nutrition of Central America and Panama (INCAP), serving as Director from 1949 to 1961. In this article, he reviews the history of the founding of INCAP, including the role of the Rockefeller and Kellogg Foundations, the Central American governments, and the Pan American Health Organization. The objectives pursued by INCAP in its early years were to assess the nutrition and related health problems of Central America, to carry out research to find practical solutions to these problems, and to provide technical assistance to its member countries to implement solutions. INCAP pursued a strategy of selecting promising Central Americans for advanced education and training in the US who assumed positions of leadership on their return. After this early phase, talented non-Central Americans of diverse origins were brought to INCAP, as well as additional researchers from the region. Growth of INCAP, as reflected in its annual budget and in the physical plant, was rapid and this was accompanied by high scientific productivity. Several field studies were launched that contributed impetus and design elements for the Oriente Longitudinal Study, which is the focus of this supplement.
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The synthesis of large numbers of antibiotics over the past three decades has caused complacency about the threat of bacterial resistance. Bacteria have become resistant to antimicrobial agents as a result of chromosomal changes or the exchange of the exchange of genetic material via plasmids and transposons. Streptococcus pneumoniae, Streptococcus pyogenes, and staphylococci, organisms that cause respiratory and cutaneous infections, and members of the Enterobacteriaceae and Pseudomonas families, organisms that cause diarrhea, urinary infection, and sepsis, are now resistant to virtually all of the older antibiotics. The extensive use of antibiotics in the community and hospitals has fueled this crisis. Mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance.
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Several species of protozoa, during their logarithmic phases of growth, produce substances that prolong the logarithmic phase in other species. The effect is not as striking as the inhibition of growth caused by antibiotics, but a consistent 50-percent increase in growth has been obtained with Tetrahymena pyriformis in response to a factor produced by Colpidium campylum.
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The growth promoting effects of antibiotics were first discovered in the 1940s. Since then, many antimicrobials have been found to improve average daily weight gain and feed efficiency. The total production of antibiotics can be estimated between 100,000-200,000 tons annually and the human population is being influenced, directly or indirectly (from the environment) by this amount of drug. The twentieth-century increase in human height and the obesity of the population is roughly observed since the mass consumption of antibiotics 40-50 years ago. The association between antibiotic consumption and the increase of human growth/obesity is suspected.
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Environmental factors, such as social networks, have an influence on obesity pandemics. The gut microbial flora (microbiota) plays a role in converting nutrients into calories. Variations in microbiota composition are found in obese humans and mice. The microbiota from an obese mouse confers an obese phenotype when transferred to an axenic mouse. There is a large body of experimental evidence and empirical data in the food industry showing that both antibiotics and probiotics, which modify the gut microbiota, can act as growth promoters, increasing the size and weight of animals. The current obesity pandemic may be caused, in part, by antibiotic treatments or colonization by probiotic bacteria. Using metagenomics and microarray analysis, studies of microbiota modifications after antibiotic and probiotic intake may identify the modifications associated with increased size and weight. Epidemiological studies recording these factors in an obese population may be able to link obesity with the absorption of microbiota modifiers.