BACKGROUND AND OBJECTIVES:Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota.

METHODS:A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)β1, TGFβ2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing.

RESULTS:Individually, immunomodulators TGFβ1 and TGFβ2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFβ1 and TGFβ2, however, were not independent of one another, and the effect of TGFβ2 was stronger than that of TGFβ1. Higher levels of TGFβ2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa.

CONCLUSIONS:Breast milk TGFβ concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFβ acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

BACKGROUND:The ingestion of a high-fat diet (HFD) and the resulting obese state can exert a multitude of stressors on the individual including anxiety and cognitive dysfunction. Though many studies have shown that exercise can alleviate the negative consequences of a HFD using metabolic readouts such as insulin and glucose, a paucity of well-controlled rodent studies have been published on HFD and exercise interactions with regard to behavioral outcomes. This is a critical issue since some individuals assume that HFD-induced behavioral problems such as anxiety and cognitive dysfunction can simply be exercised away. To investigate this, we analyzed mice fed a normal diet (ND), ND with exercise, HFD diet, or HFD with exercise.

RESULTS:We found that mice on a HFD had robust anxiety phenotypes but this was not rescued by exercise. Conversely, exercise increased cognitive abilities but this was not impacted by the HFD. Given the importance of the gut microbiome in shaping the host state, we used 16S rRNA hypervariable tag sequencing to profile our cohorts and found that HFD massively reshaped the gut microbial community in agreement with numerous published studies. However, exercise alone also caused massive shifts in the gut microbiome at nearly the same magnitude as diet but these changes were surprisingly orthogonal. Additionally, specific bacterial abundances were directly proportional to measures of anxiety or cognition.

CONCLUSIONS:Thus, behavioral domains and the gut microbiome are both impacted by diet and exercise but in unrelated ways. These data have important implications for obesity research aimed at modifications of the gut microbiome and suggest that specific gut microbes could be used as a biomarker for anxiety or cognition or perhaps even targeted for therapy.

Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

PURPOSE:The objective of this systematic review of literature was to evaluate and summarize published research that has investigated the association between exercise and gut microbial composition in mammals.

METHODS:This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The databases searched for this review included: PubMed; PubMed Central; Medline; Cumulative Index of Nursing and Allied Health Literature; Web of Science; Commonwealth Agricultural Bureaux Direct; Health Source: Nursing Academic Edition; Clinicaltrials.gov; International Prospective Register of Systematic Reviews (PROSPERO); and the Cochrane Library.

RESULTS:Twenty-five articles met the inclusion criteria: 17 rodent, one canine, two equine, and five human studies. All studies in rodents and equines included control groups; whereas only one study in humans included a control group. The remaining were cross-sectional or cohort studies. All studies in rodents controlled for dietary intake and one study in humans implemented a 3-d dietary control. Eleven studies assessed voluntary exercise and 13 studies used forced exercise. Diversification within the Firmicutes phylum was consistently observed in exercise groups across studies. There were no consistent trends within Bacteroidetes, Actinobacteria, or Proteobacteria phyla. In general, the potential interactions between exercise and diet composition and their respective influences on the intestinal microbiome were not well characterized.

CONCLUSIONS:Exercise was associated with changes in gut microbial composition, an increase in butyrate producing bacteria and an increase in fecal butyrate concentrations independent of diet in rodents and humans. The overall quality of evidence in the studies in humans was low and the risk of bias was unclear. Future studies with standardized reporting and rigorous dietary control in larger samples are needed to further determine the influence of exercise on gut microbial composition.

The antioxidant enzyme system helps protect against intense exercise-induced oxidative damage and is related to the physical status of athletes. Evidence suggests that intestinal microbiota may be an important environmental factor associated with host metabolism, physiology, and antioxidant endogenous defense. However, evidence of the effect of gut microbiota status on exercise performance and physical fatigue is limited. We investigated the association of intestinal bacteria and exercise performance in specific pathogen-free (SPF), germ-free (GF), and Bacteroides fragilis (BF) gnotobiotic mice. Endurance swimming time was longer for SPF and BF than GF mice, and the weight of liver, muscle, brown adipose, and epididymal fat pads was higher for SPF and BF than GF mice. The serum levels of glutathione peroxidase (GPx) and catalase were greater in SPF than GF mice. Serum superoxide dismutase activity was lower in BF than SPF and GF mice. In addition, hepatic GPx level was higher in SPF than GF and BF mice. Gut microbial status could be crucial for exercise performance and its potential action linked with the antioxidant enzyme system in athletes.

BACKGROUND:Intestinal dysbiosis has been proposed as a possible contributor of the development of type 2 diabetes (T2D). Indeed, commensal fungi and opportunistic bacteria stimulate the local immune system, altering intestinal permeability with consequent leaky gut, which in turn activates systemic inflammation responsible for insulin resistance. It is also well known that chronic exercise improves glucose control and diabetes-induced damage. The aim of this study was to evaluate the role of chronic exercise on gut flora composition and leaky gut in T2D stable patients.

METHODS:Thirty clinically stable patients with T2D were studied before and after a six months program of endurance, resistance and flexibility training. Metabolic and anthropometric evaluations were carried out. Gut flora and intestinal permeability were measured in stools by selective agar culture medium and molecular biology measurements of zonulin, which is the protein that modulates enterocyte tight junctions.

RESULTS:Diabetes causes significant intestinal mycetes overgrowth, increased intestinal permeability and systemic low-grade inflammation. However, exercise improved glycemia, functional and anthropometric variables. Moreover, chronic exercise reduced intestinal mycetes overgrowth, leaky gut, and systemic inflammation. Interestingly, these variables are closely correlated.

CONCLUSIONS:Exercise controls diabetes by also modifying intestinal microbiota composition and gut barrier function. This data shows an additional mechanism of chronic exercise and suggests that improving gut flora could be an important step in tailored therapies of T2D.

The gut microbiome is emerging as a key regulator of brain function and behavior and is associated with symptoms of several neurological disorders. There is emerging evidence that alterations in the gut microbiota are seen in epilepsy and in response to seizure interventions. In this review, we highlight recent studies reporting that individuals with refractory epilepsy exhibit altered composition of the gut microbiota. We further discuss antibiotic treatment and infection as microbiome-related factors that influence seizure susceptibility in humans and animal models. In addition, we evaluate how the microbiome may mediate effects of the ketogenic diet, probiotic treatment, and anti-epileptic drugs on reducing both seizure frequency and severity. Finally, we assess the open questions in interrogating roles for the microbiome in epilepsy and address the prospect that continued research may uncover fundamental insights for understanding risk factors for epilepsy, as well as novel approaches for treating refractory epilepsy.

Background:The physiological and biochemical demands of intense exercise elicit both muscle-based and systemic responses. The main adaptations to endurance exercise include the correction of electrolyte imbalance, a decrease in glycogen storage and the increase of oxidative stress, intestinal permeability, muscle damage, and systemic inflammatory response. Adaptations to exercise might be influenced by the gut microbiota, which plays an important role in the production, storage, and expenditure of energy obtained from the diet as well as in inflammation, redox reactions, and hydration status.

Methods:A systematic and comprehensive search of electronic databases, including MEDLINE, Scopus, ClinicalTrials.gov, ScienceDirect, Springer Link, and EMBASE was done. The search process was completed using the keywords:"endurance","exercise","immune response","microbiota","nutrition", and"probiotics".

Results:Reviewed literature supports the hypothesis that intestinal microbiota might be able to provide a measureable, effective marker of an athlete's immune function and that microbial composition analysis might also be sensitive enough to detect exercise-induced stress and metabolic disorders. The review also supports the hypothesis that modifying the microbiota through the use of probiotics could be an important therapeutic tool to improve athletes' overall general health, performance, and energy availability while controlling inflammation and redox levels.

Conclusion:The present review provides a comprehensive overview of how gut microbiota may have a key role in controlling the oxidative stress and inflammatory responses as well as improving metabolism and energy expenditure during intense exercise.

PURPOSE:Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection.

METHODS:Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection.

RESULTS:β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased.

CONCLUSION:These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

There is robust evidence that habitual physical activity is anti-inflammatory and protective against developing chronic inflammatory disease. Much less is known about the effects of habitual moderate exercise in the gut, the compartment that has the greatest immunological responsibility and interactions with the intestinal microbiota. The link between the two has become evident, as recent studies have linked intestinal dysbiosis, or the disproportionate balance of beneficial to pathogenic microbes, with increased inflammatory disease susceptibility. Limited animal and human research findings imply that exercise may have a beneficial role in preventing and ameliorating such diseases by having an effect on gut immune function and, recently, microbiome characteristics. Emerging data from our laboratory show that different forms of exercise training differentially impact the severity of intestinal inflammation during an inflammatory insult (for example, ulcerative colitis) and may be jointly related to gut immune cell homeostasis and microbiota-immune interactions. The evidence we review and present will provide data in support of rigorous investigations concerning the effects of habitual exercise on gut health and disease.

BACKGROUND:Obesity is a multifactor disease associated with cardiovascular disorders such as hypertension. Recently, gut microbiota was linked to obesity pathogenesisand shown to influence the host metabolism. Moreover, several factors such as host-genotype and life-style have been shown to modulate gut microbiota composition. Exercise is a well-known agent used for the treatment of numerous pathologies, such as obesity and hypertension; it has recently been demonstrated to shape gut microbiota consortia. Since exercise-altered microbiota could possibly improve the treatment of diseases related to dysfunctional microbiota, this study aimed to examine the effect of controlled exercise training on gut microbial composition in Obese rats (n = 3), non-obese Wistar rats (n = 3) and Spontaneously Hypertensive rats (n = 3). Pyrosequencing of 16S rRNA genes from fecal samples collected before and after exercise training was used for this purpose.

RESULTS:Exercise altered the composition and diversity of gut bacteria at genus level in all rat lineages. Allobaculum (Hypertensive rats), Pseudomonas and Lactobacillus (Obese rats) were shown to be enriched after exercise, while Streptococcus (Wistar rats), Aggregatibacter and Sutturella (Hypertensive rats) were more enhanced before exercise. A significant correlation was seen in the Clostridiaceae and Bacteroidaceae families and Oscillospira and Ruminococcus genera with blood lactate accumulation. Moreover, Wistar and Hypertensive rats were shown to share a similar microbiota composition, as opposed to Obese rats. Finally, Streptococcus alactolyticus, Bifidobacterium animalis, Ruminococcus gnavus, Aggregatibacter pneumotropica and Bifidobacterium pseudolongum were enriched in Obese rats.

CONCLUSIONS:These data indicate that non-obese and hypertensive rats harbor a different gut microbiota from obese rats and that exercise training alters gut microbiota from an obese and hypertensive genotype background.

INRTRODUCTION:Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate intensity continuous training (MICT) on intestinal metabolism and microbiota in insulin resistance.

METHODS:Twenty-six, sedentary subjects (prediabetic n=9, T2D n=17; age 49[SD 4] years; BMI 30.5[SD 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using PET. Gut microbiota composition was analysed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit.

RESULTS:VO2peak improved only after SIT (p=0.01). Both training modes reduced systematic and intestinal inflammatory markers (TNFα, LBP) (time p<0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time p=0.03) and decreasing Firmicutes/Bacteroidetes ratio (time p=0.04). Moreover, there was a decrease in Clostridium genus (time p=0.04) and Blautia (time p=0.051). Only MICT decreased jejunal FAU (p=0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus.

CONCLUSION:Intestinal substrate uptake associates with gut microbiota composition and activity and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.

Exercise reduces the risk of inflammatory disease by modulating a variety of tissue and cell types, including those within the gastrointestinal tract. Recent data indicates that exercise can also alter the gut microbiota, but little is known as to whether these changes affect host function. Here, we use a germ-free (GF) animal model to test whether exercise-induced modifications in the gut microbiota can directly affect host responses to microbiota colonization and chemically-induced colitis. Donor mice (n = 19) received access to a running wheel (n = 10) or remained without access (n = 9) for a period of six weeks. After euthanasia, cecal contents were pooled by activity treatment and transplanted into two separate cohorts of GF mice. Two experiments were then conducted. First, mice were euthanized five weeks after the microbiota transplant and tissues were collected for analysis. A second cohort of GF mice were colonized by donor microbiotas for four weeks before dextran-sodium-sulfate was administered to induce acute colitis, after which mice were euthanized for tissue analysis. We observed that microbial transplants from donor (exercised or control) mice led to differences in microbiotaβ-diversity, metabolite profiles, colon inflammation, and body mass in recipient mice five weeks after colonization. We also demonstrate that colonization of mice with a gut microbiota from exercise-trained mice led to an attenuated response to chemical colitis, evidenced by reduced colon shortening, attenuated mucus depletion and augmented expression of cytokines involved in tissue regeneration. Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host.

Regular physical exercise provides many health benefits, protecting against the development of chronic diseases, and improving quality of life. Some of the mechanisms by which exercise provides these effects are the promotion of an anti-inflammatory state, reinforcement of the neuromuscular function, and activation of the hypothalamic-pituitary-adrenal (HPA) axis. Recently, it has been proposed that physical exercise is able to modify gut microbiota, and thus this could be another factor by which exercise promotes well-being, since gut microbiota appears to be closely related to health and disease. The purpose of this paper is to review the recent findings on gut microbiota modification by exercise, proposing several mechanisms by which physical exercise might cause changes in gut microbiota.

Human breast milk (HBM) may have beneficial effects onDSM 17938 (LR 17938) -mediated immunomodulation. We aimed to determine the effects of HBM on proliferation of LR 17938 in vitro and its associated proteins and metabolites in culture, in order to provide mechanistic insights into the health benefits of LR 17938. LR 17938 was cultured anaerobically in MRS bacterial culture media, HBM (from 6 mothers), and 2 types of cow-milk formula. The colony-forming unit (CFU) was calculated to evaluate LR 17938 growth. Sixteen-hour-fermented supernatants were used for metabolomics, and bacterial lysates were used for proteomics analysis. We found that growth of LR 17938 was 10 times better in HBM than in formula. We detected 261/452 metabolites upregulated when LR 17938 cultured in HBM compared to in formula, mainly participating in the glyoxylate cycle (succinate), urea cycle (citrulline), methionine methylation (N-acetylcysteine), and polyamine synthesis (spermidine). The significantly up-regulated enzymes were also involved in the formation of acetyl-CoA in the glyoxylate cycle and the antioxidant N-acetylcysteine. In conclusion, HBM enhances the growth of LR 17938 compared to formula and promotes LR 17938-associated metabolites that relate to energy and antioxidant status, which may be linked to the physiological effects of.

While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.

OBJECTIVE:In 2002 we suggested a new hypothesis of migraine. This hypothesis implies that migraine is a consequence of a loss of neurohormonal and metabolic integrity. The goal of this clinical analysis is to present the evaluation of the effect of a multimodal treatment program in migraine management.

MATERIAL AND METHODS:We evaluated 30 patients ages 16-66 with migraine who were treated with a multimodal treatment program. All patients received a complex program which included: hormonorestorative therapy (HT) with bio-identical hormones; correction of balance between sympathetic and parasympathetic systems and simultaneously calcium/magnesium balance;"resetting"the pineal gland; improvement of intestinal absorption through restoration of normal intestinal flora, and a cleanse from parasitic infestation (if necessary). Serum levels of total cholesterol (TC), pregnenolone, dehydroepiandrosterone sulfate (DHEAS), progesterone, total estrogen, and total testosterone were determined,

RESULTS:All patients responded to this regimen. We do not have patients who still have migraine after they started to use this program. Laboratory finding prior to HT showed the significant deficiency in production of all basic steroid hormones (progesterone and pregnenolone production declined the most). Concurrent symptoms such as fibromyalgia, insomnia, depression, gastrointestinal disorders, and fatigue had disappeared. Total cholesterol completely normalized in 22 (91.7%) patients. No adverse effects or complications related to this program were registered.

CONCLUSIONS:Our findings support the hypothesis that migraine is a consequence of a loss of neurohormonal and metabolic integrity, and that migraine can be managed by a multimodal approach.

BACKGROUND:Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile.

FINDINGS:Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals.

CONCLUSIONS:Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model.

Microbiota is a set of microorganisms resident in gut ecosystem that reacts to psychological stressful stimuli, and is involved in depressed or anxious status in both animals and human being. Interestingly, a series of studies have shown the effects of physical exercise on gut microbiota dynamics, suggesting that gut microbiota regulation might act as one mediator for the effects of exercise on the brain. Recent studies found that gut microbiota dynamics are also regulated by metabolism changes, such as through physical exercise or diet change. Interestingly, physical exercise modulates different population of gut bacteria in compared to food restriction or rich diet, and alleviates gut syndromes to toxin intake. Gut microbiota could as well contribute to the beneficial effects of exercise on cognition and emotion, either directly through serotonin signaling or indirectly by modulating metabolism and exercise performance.

OBJECTIVE:Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and pelvis of young adults. On the HLA-B27 genetic background, the occurrence of AS is influenced by the intestinal microbiota. The goal of our study was to test whether breast feeding, which influences microbiota, can prevent the development of AS.

METHODS:First, 203 patients with HLA-B27-positive AS fulfilling the modified New York criteria were recruited in the Department of Rheumatology, Ste Marguerite hospital in Marseilles. A total of 293 healthy siblings were also recruited to make up a control group within the same families. Second, 280 healthy controls, and 100 patients with rheumatoid arthritis and their siblings were recruited. The data collected were age, gender, number of brothers and sisters, age at disease onset, type and duration of feeding (breast or bottle).

RESULTS:Patients with AS had been breast fed less often than healthy controls. In families where children were breast fed, the patients with AS were less often breast fed than their healthy siblings (57% vs 72%), giving an OR for AS onset of 0.53 (95% CI (0.36 to 0.77), p value=0.0009). Breast feeding reduced familial prevalence of AS. The frequency of breast feeding was similar in the AS siblings and in the 280 unrelated controls. However, patients with AS were less often breast fed compared with the 280 unrelated controls (OR 0.6, 95% CI (0.42 to 0.89), p<0.01).

CONCLUSIONS:Our study suggests a breastfeeding-induced protective effect on the occurrence of AS. To our knowledge, this is the first study of breastfeeding history in patients with AS.