The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study of over 23 000 diabetes-free pregnancies has shown that at a population level an unequivocal linear relationship exists between maternal glucose concentrations around the beginning of the third trimester of pregnancy and the risk of their baby being born above the ninetieth centile for weight. With the rising incidence of gestational diabetes (GDM) across the developed world, largely paralleling the increased prevalence of obesity, there has been a sharp increase in the risk of pregnancy complications developing related to the birth of macrosomic babies. The associated additional long-term complications of GDM pregnancies means that in the future there is likely to be a large increase in the incidence of type 2 diabetes and associated conditions in both the mothers and their affected offspring. The present review seeks to highlight recent advances and remaining gaps in knowledge about GDM in terms of its genetics (where some of the recently discovered polymorphic risk factors for type 2 diabetes have also proved to be risk factors for GDM) and its treatment by diet, exercise and drugs.

n-6 PUFA are well known for their critical role in many physiological functions and seem to reduce risks of CHD. However, some argue that excessive consumption of n-6 PUFA may lead to adverse effects on health and therefore recommend reducing dietary n-6 PUFA intake or fixing an upper limit. In this context, the present work aimed to review evidence on the link between n-6 PUFA and risks of CVD. Epidemiological studies show that n-6 PUFA dietary intake significantly lowers blood LDL-cholesterol levels. In addition, n-6 PUFA intake does not increase several CVD risk factors such as blood pressure, inflammatory markers, haemostatic parameters and obesity. Data from prospective cohort and interventional studies converge towards a specific protective role of dietary n-6 PUFA intake, in particular linoleic acid, against CVD. n-6 PUFA benefits are even increased when SFA intake is also reduced. In regards to studies examined in this narrative review, recommendation for n-6 PUFA intake above 5 %, and ideally about 10 %, of total energy appears justified.

The aim of diabetes management is to normalise blood glucose levels since improved blood glucose control is associated with fewer complications. Food affects blood glucose levels; however, there is no universal approach to the optimal diabetic diet and there is controversy about the usefulness of the low-glycaemic index (GI) diet. To assess the effects of low-GI diets on glycaemic control in diabetes, we conducted electronic searches of the Cochrane Library, MEDLINE, EMBASE and CINAHL. We assessed randomised controlled trials (RCT) with interventions >4 weeks that compared a low-GI diet with a higher-GI diet for type 1 or type 2 diabetes. Twelve RCT (n 612) were identified. There was a significant decrease in glycated Hb (HbA1c) with low-GI diet than with the control diet, indicating improved glycaemic control (seven trials, n 457, weighted mean difference (WMD) − 0·4 % HbA1c, 95 % CI − 0·7, − 0·20, P = 0·001). In four studies reporting the results for glycaemic control as fructosamine, three of which were 6 weeks or less in duration, pooled data showed a decrease in fructosamine (WMD − 0·23 mmol/l, 95 % CI − 0·47, 0·00, P = 0·05), n 141, with low-GI diet than with high-GI diet. Glycosylated albumin levels decreased significantly with low-GI diet, but not with high-GI diet, in one study that reported this outcome. Lowering the GI of the diet may contribute to improved glycaemic control in diabetes.

It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mm in 0·9 % saline) or control (0·9 % saline) at 4 ml/min for 150 min (T = − 30 to 120 min). After 30 min (T = 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2·5 %), were co-infused intraduodenally (T = 0–120 min; 4·2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagon-like peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P < 0·005 for each). However, there were no differences in blood glucose, plasma GLP-1 or serum 3-OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.

The objective of the present study was to evaluate the effect of Lactobacillus acidophilus 4356 on cholesterol metabolism in vivo. Rats were fed a cholesterol-enriched experimental diet with or without L. acidophilus 4356 supplementation at a dose of 109 colony-forming units per d. L. acidophilus 4356 feeding significantly lowered total serum cholesterol, LDL-cholesterol and TAG concentrations, but there was no change in the serum HDL-cholesterol concentrations. In addition, total liver cholesterol and TAG were decreased in the L. acidophilus 4356-fed group. The expression of Niemann-Pick C1-Like 1 (NPC1L1) in the duodenum and jejunum was significantly decreased following L. acidophilus 4356 feeding. Lactobacillus acidophilus 4356 increased the population of lactobacilli and bifidobacteria in the small intestine and faeces compared with the control. These results indicate that the probiotic potential of the L. acidophilus 4356 strain in the control of cholesterol is at least partially mediated by the down-regulation of NPC1L1. Furthermore, these results also potentially suggest a new mechanism that is responsible for the cholesterol-reducing effects of probiotics.

Evaluations of molecular mechanisms of dietary plants with their active molecules are essential for the complete exploration of their nutritive and therapeutic value. In the present study, we investigated the effect of chicory (Cichorium intybus) salad leaves in inhibiting protein tyrosine phosphatase 1B (PTP1B), and evaluated their role in modulating the key markers involved in insulin cell signalling and adipogenesis using 3T3-L1 adipocytes. Bioactivity-directed purification studies enlightened the additive effects of chlorogenic acid (CGA) along with other caffeic acid derivatives present in methanolic extract of C. intybus (CME). Incubation of CME and CGA with 3T3-L1 adipocytes significantly enhanced the 2-deoxy-d-3[H]-glucose uptake and inhibited adipogenesis through altering the expressions of insulin signalling and adipogenesis markers. Extending to an in vivo model, the effect of CME was also investigated on insulin sensitivity in high-fat diet with low streptozotocin-induced diabetic rats. Supplementation of CME for 2 weeks reinstated the insulin sensitivity along with plasma metabolic profile. The present results demonstrate that the caffeoyl derivatives of chicory salad leaves show promising pharmacological effect on energy homoeostasis via PTP1B inhibition both in vitro and in vivo.

Consumption of grape seed extract (GSE) is widely marketed as a dietary supplement and is considered safe for human health. Nevertheless, the analytical composition of GSE from different grape cultivars, growing in special agronomic constraints, differs greatly in flavan-3-ols content. The major concern with GSE studies is a lack of availability of uniformly standardised preparations, which raises an important question whether different GSE samples have comparable activity and trigger the same mechanisms of action on a given biological system. Therefore, it is tempting to speculate that GSE, obtained from different cultivars, could exert differentiated anticancer effects. The focus of the present study is to determine the selective biological efficacy of GSE obtained from three different sources on the human colon cancer cell line Caco-2. Irrespective of its source, high doses of GSE induced a significant inhibition on Caco-2 cell growth. Moreover, apoptosis was enhanced through both caspase-dependent and caspase-independent mechanisms, leading to an early apoptosis-inducing factor release and, further, to a dramatic increase in caspase 7 and 3 activity. However, a significant difference in apoptotic rates induced by the three grape sources clearly emerged when treating cancer cells with low and intermediate GSE concentrations (25 and 50 μg/ml).

Limited information is available on lignan metabolism and tissue distribution between sexes and the effects of prolonged lignan exposure on tissue concentrations. In the present study, excretion and tissue distribution of lignans were compared after 1 d and 7 d administration of flaxseed lignan secoisolariciresinol diglycoside (SDG) in male and female rats. Sprague–Dawley rats were daily gavaged per os with 3H-SDG (3·7 kBq/g body weight (bwt)) and unlabelled SDG (5·3 μg/g bwt). Urine, faeces, serum and tissues (liver, kidneys, bladder, spleen, lungs, brain, thymus, heart, muscle, adipose, mammary gland, ovaries, vagina, uterus, testis, seminal vesicles, coagulating glands and ventral prostate) were collected at 0, 12 and 24 h after a single lignan dose or after the last dose of 7 d exposure. The sample total lignan content was measured as radioactivity by liquid scintillation counting. In both sexes, majority of radioactivity was excreted in faeces (40–83 %) and urine (1·2–5·2 %). 3H-SDG administration increased radioactivity in all tissues at all time points, and the levels were further increased after prolonged SDG exposure. Liver contained majority of the tissue lignans (48–56 %) in both sexes after both exposure regimens. After prolonged SDG exposure, the serum lignan concentrations had reached a plateau which was approximately 4-fold of that of acute exposure, whereas in both sexes, concentrations in skin and kidneys still increased, indicating tissue accumulation. After prolonged exposure, females had higher lignan concentrations in heart and thymus at all time points, demonstrating sex-related differences in lignan tissue distribution and the possibility for sex-specific treatment responses. These findings facilitate identification of target tissues for local lignan actions in vivo.

Maternal nutritional status, e.g. body weight and composition, is associated with fetal growth. It has been suggested that the insulin-like growth factor (IGF) system may be a mediator of this relationship. In twenty-three healthy Swedish women, we studied (1) the relationships before and during pregnancy between maternal serum concentrations of IGF-I and IGF binding protein-1 (IGFBP-1) and maternal body weight and composition; (2) interactions between serum concentrations of IGF-I (before and in early pregnancy) and maternal nutritional status in relation to infant birth weight. We found that serum IGF-I during pregnancy was positively correlated with maternal body weight (r 0·47–0·56) and fat-free body weight (r 0·61–0·65), whereas serum IGFBP-1 was negatively correlated with maternal body weight (r − 0·44 to − 0·69) and body fat (r − 0·64 to − 0·76) before and during pregnancy. Women with a lower body fat content (%) before pregnancy had greater increases in serum IGFBP-1 during pregnancy than women with a higher prepregnant body fat content (%). In addition, significant fractions of the variation in corrected infant birth weight were explained by variables related to the maternal nutritional status when these were combined with serum concentrations of IGF-I in gestational week 14 (adjusted r2 0·25–0·44, P = 0·001–0·021), but not when they were combined with such concentrations before pregnancy (adjusted r2 0·11–0·12, P = 0·105–0·121). These results suggest mechanisms by which the IGF system may be a mediator between maternal nutritional status and fetal growth.

Quercetin, a flavonoid found in fruits and vegetables, is a strong antioxidant with anti-inflammatory, antimicrobial and immune-modulating properties. The purpose of the present study was to investigate the effects of long-term quercetin supplementation on innate immune function and inflammation in human subjects. Female subjects (n 120; aged 30–79 years) were recruited from the community and randomised to one of three groups, with supplements administered using double-blinded procedures: 500 mg quercetin/d (n 38), 1000 mg quercetin/d (n 40) or placebo (n 42). Subjects ingested two soft chew supplements twice daily during the 12-week study period. Fasting blood samples were obtained pre- and post-study and were analysed for plasma quercetin, IL-6, TNF-α and leucocyte subset cell counts. Natural killer cell activity (NKCA) and lymphocyte subsets were assessed in a subset of seventy-four subjects. Granulocyte oxidative burst activity (GOBA) and phagocytosis were assessed in sixty-four subjects. Eighteen subjects had overlapping data. Quercetin supplementation at two doses compared with placebo increased plasma quercetin (interaction effect; P < 0·001) but had no significant influence on blood leucocyte subsets, plasma IL-6 or TNF-α concentration, NKCA, GOBA or phagocytosis. NKCA was inversely correlated with BMI (r − 0·25; P = 0·035) and body fat percentage (r − 0·38; P = 0·001), and positively correlated with self-reported physical fitness level (r 0·24; P = 0·032). In summary, results from the present double-blinded, placebo-controlled, randomised trial indicated that quercetin supplementation at 500 and 1000 mg/d for 12 weeks significantly increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in community-dwelling adult females.

The absorption and plasma disappearance of vitamin K were investigated by uniformly labelling phylloquinone in kale with carbon-13, and by feeding the kale to study subjects. Seven healthy volunteers ingested a single 400 g serving of kale with 30 g vegetable oil. The kale provided 156 nmol of phylloquinone. Serial plasma samples were collected and analysed for the appearance of 13C-phylloquinone by HPLC–MS. Six of the subjects showed significant amounts of labelled phylloquinone in plasma, though one subject's plasma was not consistently enriched above the detection limit, and this subject's baseline plasma phylloquinone level was the lowest in the group. After ingestion of the labelled kale, plasma 13C-phylloquinone concentration increased rapidly to a peak between 6 and 10 h, and then rapidly decreased. Average peak plasma concentration for the six subjects with detectable 13C-phylloquinone was 2·1 nmol/l. Plasma concentration–time data were analysed by compartmental modelling. Modelling results demonstrated a mean (n 6) bioavailability of phylloquinone from kale to be 4·7 %. Plasma and tissue half-times for phylloquinone were found to be 8·8 and 215 h, respectively.

Postprandial lipaemia impairs endothelial function, possibly by changes in oxidative stress, but whether this affects cardiac output and/or systemic vascular resistance (SVR) at rest and in response to dynamic exercise remains uncertain. The present study set out to investigate the effects of a high-fat meal (HFM) v. a low-fat, high-carbohydrate meal (HCM) on cardiac output and SVR. A HFM (50 g fat) and an isoenergetic HCM (5 g fat) were randomly fed to thirty healthy adults using a crossover design. Cardiac output, heart rate and blood pressure (BP) were measured, and stroke volume and SVR were calculated over a 3 h rest following the meal, during exercise 3 h postprandially and for 45 min post-exercise. Blood samples were collected at fasting, 3 h postprandially and immediately post-exercise. Plasma TAG increased by 63·8 % 3 h following the HFM, and NEFA fell by 94·1 % 3 h after the HCM. There was a 9·8 % rise in plasma 8-isoprostane-F2α concentration following the HFM, and a 6·2 % fall following the HCM. Cardiac output increased postprandially, but the difference between meals at rest or exercise was not statistically significant. The HFM resulted in a 3·2 mmHg (95 % CI 0·7, 5·7) smaller increase in exercise mean arterial BP compared with the HCM due to a greater fall in exercise SVR. Postprandial lipaemia induced by a HFM does not affect cardiac output and/or SVR at rest, but it blunts the increase in BP during exercise.

Clinical research shows that nutritional intervention is necessary to prevent malnutrition in head and neck cancer patients undergoing radiotherapy. The objective of the present study was to assess the value of individually adjusted counselling by a dietitian compared to standard nutritional care (SC). A prospective study, conducted between 2005 and 2007, compared individual dietary counselling (IDC, optimal energy and protein requirement) to SC by an oncology nurse (standard nutritional counselling). Endpoints were weight loss, BMI and malnutrition (5 % weight loss/month) before, during and after the treatment. Thirty-eight patients were included evenly distributed over two groups. A significant decrease in weight loss was found 2 months after the treatment (P = 0·03) for IDC compared with SC. Malnutrition in patients with IDC decreased over time, while malnutrition increased in patients with SC (P = 0·02). Therefore, early and intensive individualised dietary counselling by a dietitian produces clinically relevant effects in terms of decreasing weight loss and malnutrition compared with SC in patients with head and neck cancer undergoing radiotherapy.

The association between hyporexia/anorexia, reduced food intake and disease-related malnutrition at hospital admission is well established. However, information on fluid intake according to nutritional risk has never been provided. Thus, we assessed the attitude and adequacy of fluid intake among case-mix hospitalised patients according to nutritional risk. A sample of 559 non-critically ill patients randomly taken from medical and surgical wards was evaluated. Nutritional risk was diagnosed by the Nutritional Risk Screening 2002. Usual fluid consumption the week before admission was assessed and categorised as < 5 and ≥ 5 cups/d (1 cup = 240 ml), with the acceptable intake being ≥ 5 cups/d. Prevalence of nutritional risk was 57·2 %, and 46·2 % of the patients reported a fluid intake < 5 cups/d. Multiple-adjusted logistic regression revealed that age ≥ 65 years (OR: 1·88 (95 % CI: 1·03, 3·43); P < 0·04), energy intake (for every 25 % increase in food intake compared with estimated requirements, OR: 0·37 (95 % CI: 0·25, 0·55); P < 0·001) and the number of drugs taken (every three-drug increase, OR: 0·63 (95 % CI: 0·44, 0·90); P < 0·02) were independently associated with inadequate fluid intake ( < 5 cups/d). A significant independent association was also found with nutritional risk (OR: 0·64 (95 % CI: 0·43, 0·95); P < 0·03). Nutritional risk appears to be positively associated with greater fluid intake in non-acute hospitalised patients, but both the reasons and the consequences of this relationship, as well as the impact on clinical practice, need to be explored. However, water replacement by oral nutritional support should take advantage of the patients' attitude to assuming a greater fluid intake, limiting at the same time fluid overload during the refeeding phase.

To investigate the part played by undernutrition in malaria severity, some biomarkers of nutritional status were assessed in children with severe malarial anaemia (MA) and cerebral malaria (CM) in comparison with healthy children or those with uncomplicated malaria. Undernutrition was assessed using the weight-for-age Z score (WAZ). Retinol was determined by HPLC; lipid profile, Ca, Mg and albumin were determined by spectrophotometry. Severe and moderate undernutritions were more prevalent in children with MA and those with the combined symptoms of CM and MA, but not in those with CM alone. Some perturbations were noticed in the lipid profile, but most of the values remained within the normal ranges. The risk of vitamin A deficiency, as assessed by plasma retinol concentration, was noteworthy in children with severe malaria: 0·48 × 10− 6 and 0·50 × 10− 6 mol/l, respectively, in children with MA and CM (reference value: >0·7 × 10− 6 mol/l). A significant difference was obtained for retinol values after an ANOVA of all the groups (P = 0·0029), with the value in the MA group being significantly low than that in the control group (P < 0·05); likewise, a significant difference was obtained after comparison of all the groups for Mg and albumin (P = 0·0064 and 0·0082, respectively). Despite their low number (n 6), fatal cases of CM had a normal mean WAZ on admission, but low values of retinol, albumin and HDL:LDL ratio. Despite these associations, undernutrition itself did not appear to be a primary factor associated with fatal outcome.

Predictive power, for total and vascular mortality, of selected indices measured at baseline in the British National Diet and Nutrition Survey (community-living subset) of People Aged 65 Years and Over was tested. Mortality status and its primary and underlying causes were recorded for 1100 (mean age 76·7 (sd 7·5) years, 50·2 % females) respondents from the baseline survey in 1994–5 until September 2008. Follow-up data analyses focussed especially on known predictors of vascular disease risk, together with intakes and status indices of selected nutrients known to affect, or to be affected by, these predictors. Total mortality was significantly predicted by hazard ratios of baseline plasma concentrations (per sd) of total homocysteine (tHcy) (95 % CI) 1·19 (1·11, 1·27), pyridoxal phosphate 0·90 (0·81, 1·00), pyridoxic acid 1·10 (1·03, 1·19), α1-antichymotrypsin 1·21 (1·13, 1·29), fibrinogen 1·14 (1·05, 1·23), creatinine 1·20 (1·10, 1·31) and glycosylated Hb 1·23 (1·14, 1·32), and by dietary intakes of energy 0·87 (0·80, 0·96) and protein 0·86 (0·77, 0·97). Prediction patterns and significance were similar for primary-cause vascular mortality. The traditional risk predictors plasma total and HDL cholesterol were not significant mortality predictors in this age group, nor were the known tHcy-regulating nutrients, folate and vitamin B12 (intakes and status indices). Model adjustment for known risk predictors resulted in the loss of significance for some of the afore-mentioned indices; however, tHcy 1·34 (1·04, 1·73) remained a significant predictor for vascular mortality. Thus, total and primary vascular mortality is predicted by energy and protein intakes, and by biochemical indices including tHcy, independent of serum folate or vitamin B12.

Clinical manifestations of lactase (LCT) deficiency include intestinal and extra-intestinal symptoms. Lactose hydrogen breath test (H2-BT) is considered the gold standard to evaluate LCT deficiency (LD). Recently, the single-nucleotide polymorphism C/T− 13 910 has been associated with LD. The objectives of the present study were to evaluate the agreement between genetic testing of LCT C/T− 13 910 and lactose H2-BT, and the diagnostic value of extended symptom assessment. Of the 201 patients included in the study, 194 (139 females; mean age 38, range 17–79 years, and 55 males, mean age 38, range 18–68 years) patients with clinical suspicion of LD underwent a 3–4 h H2-BT and genetic testing for LCT C/T− 13 910. Patients rated five intestinal and four extra-intestinal symptoms during the H2-BT and then at home for the following 48 h. Declaring H2-BT as the gold standard, the CC− 13 910 genotype had a sensitivity of 97 % and a specificity of 95 % with a κ of 0·9 in diagnosing LCT deficiency. Patients with LD had more intense intestinal symptoms 4 h following the lactose challenge included in the H2-BT. We found no difference in the intensity of extra-intestinal symptoms between patients with and without LD. Symptom assessment yielded differences for intestinal symptoms abdominal pain, bloating, borborygmi and diarrhoea between 120 min and 4 h after oral lactose challenge. Extra-intestinal symptoms (dizziness, headache and myalgia) and extension of symptom assessment up to 48 h did not consistently show different results. In conclusion, genetic testing has an excellent agreement with the standard lactose H2-BT, and it may replace breath testing for the diagnosis of LD. Extended symptom scores and assessment of extra-intestinal symptoms have limited diagnostic value in the evaluation of LD.

Traditional analysis of food intake usually fails to show an association between energy and nutrient intake and indicators of obesity. The analysis of food patterns can contribute to the understanding of the association between eating habits and anthropometric indicators. A population-based cross-sectional study was carried out on a low-income neighbourhood in the Rio de Janeiro metropolitan area, and 1009 subjects between 20 and 65 years of age completed an FFQ. Dietary patterns were identified by means of factor analysis, and their associations with BMI and waist circumference (WC) were ascertained by applying a linear regression analysis. Three main dietary patterns were identified: a mixed pattern, which included cereals, fish and shrimp, vegetables, roots, fruits, eggs, meat and caffeinated beverages; a Western pattern, which consisted of ‘fast foods’, soft drinks, juices, cakes, cookies, milk and dairy, sweets and snacks; a traditional pattern, which included rice, beans, bread, sugar, fats and salad dressings. After adjusting for age and energy intake, we found that the traditional dietary pattern was inversely associated with BMI (β = − 1·14, P < 0·001) and WC (β = − 14·9, P = 0·002) among females. Additionally, a positive association between the Western pattern and WC (β = 12·8, P = 0·02) was observed for females. A diet based on rice and beans may have a protective role against weight gain in women.

Human subjects obtain their vitamin D from the diet, especially from marine food, and from endogenous synthesis following cutaneous sun exposure. The risk of an insufficient vitamin D synthesis is increased in northern populations, but it may be counteracted by a high intake of marine food in fishing populations, e.g. at the Faroe Islands. We examined the vitamin D status and its statistical determinants in a cross-sectional study of 713 elderly Faroese aged 70–74 years, about two-thirds of all the eligible residents in this age group. Clinical examination included measurement of body weight and height, and marine food intake was estimated using a questionnaire. We measured serum 25-hydroxyvitamin D3 (S-25(OH)D3) by LC-MS/MS in 669 of the 713 subjects in whom sufficient serum was available. Of the population, 19 % had S-25(OH)D3 concentrations < 25 nmol/l, and only 10·3 % of the population had S-25(OH)D3 concentrations >80 nmol/l. In a logistic regression analysis, BMI < 30 kg/m2, blood sampling in summer season, eating pilot whale blubber more than once per month and female sex were positively associated with vitamin D levels >80 nmol/l. The high prevalence of low vitamin D levels among the elderly Faroese population reflects the low skin synthesis during most months of the year, which is caused by the limited sun exposure and insufficient benefits from marine diet. Thus, even in a population with a high intake of marine food, the northern latitude causes a low vitamin D status. Efforts to improve vitamin D status in this population are warranted.

The gut microbiota has been implicated in host nutrient absorption and energy homeostasis. We studied the influence of different diets on body composition in germ-free (GF) and conventional (CV) mice. GF and CV male adult C3H mice were fed ad libitum a semi-synthetic low-fat diet (LFD; carbohydrate–protein–fat ratio: 41:42:17; 19·8 kJ/g), a high-fat diet (HFD; 41:16:43; 21·4 kJ/g) or a commercial Western diet (WD; 41:19:41; 21·5 kJ/g). There was no difference in body weight gain between GF and CV mice on the LFD. On the HFD, GF mice gained more body weight and body fat than CV mice, and had lower energy expenditure. GF mice on the WD gained significantly less body fat than GF mice on the HFD. GF mice on both HFD and WD showed increased intestinal mRNA expression of fasting-induced adipose factor/angiopoietin-like protein 4 (Fiaf/Angptl4), but they showed no major changes in circulating Fiaf/Angptl4 compared with CV mice. The faecal microbiota composition of the CV mice differed between diets: the proportion of Firmicutes increased on both HFD and WD at the expense of the Bacteroidetes. This increase in the Firmicutes was mainly due to the proliferation of one family within this phylum: the Erysipelotrichaceae. We conclude that the absence of gut microbiota does not provide a general protection from diet-induced obesity, that intestinal production of Fiaf/Angptl4 does not play a causal role in gut microbiota-mediated effects on fat storage and that diet composition affects gut microbial composition to larger extent than previously thought.