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Alterations of gut microbiota are associated with blood pressure: a cross-sectional clinical trial in Northwestern China.
Lv, J, Wang, J, Yu, Y, Zhao, M, Yang, W, Liu, J, Zhao, Y, Yang, Y, Wang, G, Guo, L, et al
Journal of translational medicine. 2023;21(1):429
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Hypertension (HTN) is a complex and modifiable risk factor for cardiovascular diseases (CVDs) and stroke, while a diverse range of endogenous and environmental factors contribute to both HTN onset and progression. The adult gut microbiota (GM) consists of trillions of microorganisms and maintains the gut immunity and whole-body homeostasis. The aim of this study was to investigate the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. This study was a cross-sectional study. Participants were randomly selected for the HTN and control groups. A total of 36 HTN subjects (24 females and 12 males) and 18 controls (9 females and 9 males) were randomly selected for metagenomic analysis. Results showed a positive association between GM characteristics and alterations and HTN in both females and males. Thus, GM dysbiosis underlies HTN pathogenesis. Authors conclude that further studies are needed to elucidate the underlying mechanisms and potential therapeutic interventions targeting GM for HTN prevention and management
Abstract
BACKGROUND The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .
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Time-restricted feeding's effect on overweight and obese patients with chronic kidney disease stages 3-4: A prospective non-randomized control pilot study.
Lao, BN, Luo, JH, Xu, XY, Fu, LZ, Tang, F, Ouyang, WW, Xu, XZ, Wei, MT, Xiao, BJ, Chen, LY, et al
Frontiers in endocrinology. 2023;14:1096093
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Obesity is a chronic metabolic disease caused by multiple factors. It is an independent risk factor for the development and progression of chronic kidney disease (CKD). The aim of this study was to explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD. This study was a prospective, non-randomised, controlled exploratory intervention study. Twenty-eight participants were included in the study, and were assigned to either the time-restricted feeding (TRF) group or the control diet (CD) group according to their preferences. Results showed that: - TRF helped improve renal function in overweight and obese moderate-to-severe CKD patients. - the TRF group experienced some hunger, but within tolerable range, and stated that TRF adherence was good. - the TRF group experienced a decrease in serum phosphate and uric acid, maintenance of total protein and albumin. - TRF shifted the gut microbiota in a positive direction. Authors concluded that TRF may be a safe and effective dietary intervention for overweight and obese CKD patients.
Abstract
BACKGROUND Time-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy. METHODS This is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks. RESULTS The change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 μmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction. CONCLUSION Preliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.
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Relationship between energy availability, energy conservation and cognitive restraint with performance measures in male endurance athletes.
Jurov, I, Keay, N, Hadžić, V, Spudić, D, Rauter, S
Journal of the International Society of Sports Nutrition. 2021;18(1):24
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Athletes who do endurance exercise sometimes experience low energy availability which can affect their performance. Low energy availability may lead to a syndrome called Relative energy deficiency in sports. This cross-sectional controlled study assessed the pre-race energy availability in twelve lean, healthy endurance athletes without pre-existing signs of relative energy deficiency. Results showed that two-thirds of the participants had low mean energy availability. Lower energy availability was associated with higher energy expenditure. Participants in the study deliberately restricted their energy intake to achieve an optimal body composition. This may have led to energy conservation in participants. However, the study failed to show any associations between energy conservation and energy availability. There is a need for more robust studies to determine the true cut-off value of energy availability in male endurance athletes. Healthcare professionals can use the results of this study to understand the need for eating behaviour screening to reduce disordered eating in endurance athletes and the clinical applicability of energy conservation assessment.
Abstract
BACKGROUND Low energy availability in male athletes has gained a lot of attention in recent years, but direct evidence of its effects on health and performance is lacking. The aim of this research was to objectively measure energy availability (EA) in healthy male endurance athletes without pre-existing relative energy deficiency signs during pre-race season. METHODS Twelve trained endurance athletes (performance level 3, 4, and 5) participated in the cross-sectional controlled laboratory study. Fat-free mass, exercise energy expenditure, and energy intake were measured to calculate EA. Resting energy expenditure was measured and estimated to assess energy conservation. Three specific performance tests were used to assess endurance, agility, and explosive strength performance. For psychological evaluation, the Three Factor Eating Questionnaire and a short Well-being questionnaire were completed. RESULTS Mean EA was 29.5 kcal/kg FFM/day. The majority (66.6%) had EA under the threshold for low EA in females. Critical cognitive restraint (≥13) was reported by 75% of participants. There were no differences in performance, blood values, or psychological evaluation when subjects were divided into two groups divided by EA = 30 kcal/kg FFM/day. Cognitive restraint was negatively associated with measured resting energy expenditure and energy conservation (r = -.578, p = .025 and r = -.549, p = .032, respectively). CONCLUSIONS The mean EA measured in this study supports the theory that the threshold for low EA in endurance male athletes might be under the threshold for females. In addition, we confirmed cognitive restraint could be useful for early detection of energy conservation. The high cognitive restraint as measured in our sample stressed the need of eating behavior screening in endurance athletes in order to reduce risk of any disordered eating patterns.
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Effects of Roux-en-Y Gastric Bypass on Osteoclast Activity and Bone Density in Morbidly Obese Patients with Type 2 Diabetes.
Tangalakis, LL, Tabone, L, Spagnoli, A, Muehlbauer, M, Omotosho, P, Torquati, A
Obesity surgery. 2020;30(1):290-295
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Gastric surgery and the resultant weight loss can improve an individual’s outcomes in a number of diseases, such as heart disease and type 2 diabetes, however an unfortunate side effect is bone loss. Roux-en-Y gastric bypass is a process whereby the size of your stomach is significantly reduced, and it is unclear as to the effect this type of surgery has on bone density. This cohort study of sixty-one individuals who underwent Roux-en-Y gastric bypass aimed to determine the effect on bone density one year post surgery. The results showed that following surgery, bone resorption was increased compared to control and although bone density was similar between the two groups, bone mineral content and bone surface area were decreased. Women who were post-menopausal demonstrated diminished bone health, although this was not significant. It was concluded that Roux-en-Y gastric bypass surgery results in a negative impact on bone health. This study could be used by healthcare professionals to understand the importance of considering bone health when recommending surgery, especially in those at high-risk of bone loss such as post-menopausal women.
Abstract
INTRODUCTION Roux-en-Y gastric bypass (RYGB) is a well-established treatment for morbid obesity and type 2 diabetes. The effects of RYGB on bone metabolism and bone health are largely unknown. OBJECTIVE Determine the changes in osteoclast function and bone density 1 year after RYGB as compared with a control group undergoing a diabetes support and education program (DSE). DESIGN A prospective cohort study with patients matched for weight and age assigned to RYGB or DSE. SETTING Large academic institution. PATIENTS OR OTHER PARTICIPANTS Patients with type 2 diabetes mellitus and morbid obesity (body mass index greater than 35 kg/m2). INTERVENTION Subjects either received laparoscopic RYBG or DSE, which consisted of nutritional, exercise, and dietary counseling performed by a certified diabetic educator and a nutritionist three times over a year. MAIN OUTCOME MEASURE Osteoclast activity, bone mineral density. RESULTS One year after, intervention subjects undergoing RYGB have a 280% increase in osteoclast activity as compared with a 7.6% increase in the DSE control group (P < 0.001). Furthermore, there was a statistically significant increase in sclerostin levels in subjects undergoing RYGB compared with an increase in the control group. The total bone mineral density was statistically unchanged within 1 year of intervention in both groups. A statistically significant decrease in bone mineral density in the left ribs (decrease of 6.8%, P < 0.05) and lumbar spine (decrease of 4.0%, P < 0.05) was seen 1 year after RYGB. CONCLUSIONS There is a significant increase in osteoclast activity observed 1 year after RYGB; the long-term clinical implications of this increased bone metabolism are unknown.
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Food-specific IgGs Are Highly Increased in the Sera of Patients with Inflammatory Bowel Disease and Are Clinically Relevant to the Pathogenesis.
Xiao, N, Liu, F, Zhou, G, Sun, M, Ai, F, Liu, Z
Internal medicine (Tokyo, Japan). 2018;57(19):2787-2798
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Inflammatory bowel disease (IBD) is an umbrella term incorporating ulcerative colitis (UC) and Crohn’s disease (CD). The exact reasons for the development of IBD are still being debated, however food allergy has been implicated. Diagnosis of food allergy is normally performed looking at the body’s immediate immune response, however the delayed immune response may be of importance in IBD. This study of 301 patients with IBD and 178 healthy controls aimed to look at the delayed immune response of individuals with IBD following the introduction of certain foods. It also looked at the efficacy of a drug treatment, infliximab (IFX) on this immune response. The results showed that the delayed immune response to egg, milk, wheat, corn, rice, tomato, codfish, and soya was increased in those with CD compared to those with UC and healthy control. Infliximab treatment was effective in suppressing this immune response in individuals with CD. It was concluded that in individuals with IBD, measuring the delayed immune response to foods may be an important diagnosis and management tool. This study could be used by healthcare professionals to understand that measuring the immediate immune response to certain foods in individuals with IBD, may not be sufficient. Measuring the delayed immune response in combination with the immediate immune response may give a better picture of foods which should be avoided in those with IBD. Infliximab treatment may be an effective treatment in patients with IBD and a delayed immune response to certain foods.
Abstract
Objective Dietary antigens are common luminal antigens in the gastrointestinal tract and have been considered to contribute to the pathogenesis of inflammatory bowel disease (IBD). We analyzed the levels of food-specific IgGs against a variety of dietary antigens, explored the clinical relevance of food allergy to the pathogenesis of IBD, and investigated whether or not infliximab (IFX) treatment could regulate the immune responses induced by dietary antigens. Methods A total of 301 IBD patients, including 201 patients with Crohn's disease (CD) and 100 patients with ulcerative colitis (UC), were recruited, and their serum food-specific IgGs against 14 food antigens were detected by a semi-quantitative enzyme linked immunosorbent assay (ELISA). Total serum IgG and IgE levels were measured by immunonephelometry and fluorescent enzyme immunoassay, respectively. Simultaneously, the relevant medical records and clinical data were collected for further analyses. Results Food-specific IgGs against egg, milk, wheat, corn, rice, tomato, codfish, and soybean antigens were found to be significantly increased in the sera of CD patients compared with UC patients and healthy controls (p<0.01). The levels of total serum IgG and IgE were also significantly higher in CD patients than in healthy controls (p<0.01). The titers of corn- and tomato-specific IgGs were found to be significantly correlated with total serum IgG in CD patients (p<0.05), while the titers of egg-, milk-, and wheat-specific IgGs were correlated with total serum IgE (p<0.05). Interestingly, IFX therapy was able to down-regulate the food-specific IgG-mediated immune response markedly in active CD patients. Conclusion Food-specific IgGs against egg, milk, wheat, corn, rice, tomato, codfish, and soybean are highly increased in the sera of CD patients. IFX treatment was able to down-regulate the levels of food-specific IgGs by suppressing intestinal inflammation and promoting mucosal healing. Therefore, food-specific IgGs may serve as an important approach in the diagnosis and management of food allergy in IBD.
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Beneficial Effects of a Dietary Weight Loss Intervention on Human Gut Microbiome Diversity and Metabolism Are Not Sustained during Weight Maintenance.
Heinsen, FA, Fangmann, D, Müller, N, Schulte, DM, Rühlemann, MC, Türk, K, Settgast, U, Lieb, W, Baines, JF, Schreiber, S, et al
Obesity facts. 2016;9(6):379-391
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Recent findings have suggested that the composition of the gut microbiome plays an important role in energy balance and metabolism. The aim of this study was to examine if weight loss altered the gut micriobiota diversity and to determine whether these changes were sustained during a weight maintenance period. Dietary intervention included a very low calorie diet (800 kcal/day) for three months followed by a weight maintenance period for three months. This study consisted of three groups – an intervention of 18 obese adults, a control of 13 lean adults and a second control of 13 obese adults. This study found that a very low calorie diet intervention in obese humans over a three-month period resulted in a significant change in microbiome diversity and metabolism, however these changes diminished during the weight maintenance period. Based on these findings, the authors suggest that nutritional components may exert a stronger effect on the human gut microbiome than changes in body weight or metabolism.
Abstract
OBJECTIVE In the present study, we examined the effect of a very low-calorie diet(VLCD)-based obesity program on human gut microbiome diversity and metabolism during weight loss and weight maintenance. METHODS Obese subjects underwent 3 months of VLCD followed by 3 months of weight maintenance. A lean and an obese control group were included. The microbiome was characterized by performing high-throughput dual-indexed 16S rDNA amplicon sequencing. RESULTS At baseline, a significant difference in the Firmicutes/Bacteroidetes ratio between the lean and obese individuals was observed (p = 0.047). The VLCD resulted in significant alterations in gut microbiome diversity from baseline to 3 months (p = 0.0053). Acinetobacter represented an indicator species for the observed effect (indicator value = 0.998, p = 0.006). Metabolic analyses revealed alterations of the bacterial riboflavin pathway from baseline to 3 months (pnom = 0.0078). These changes in diversity and bacterial metabolism induced by VLCD diminished during the weight maintenance phase, despite sustained reductions in body weight and sustained improvements of insulin sensitivity. CONCLUSION The present data show that a VLCD is able to beneficially alter both gut microbiome diversity and metabolism in obese humans, but that these changes are not sustained during weight maintenance. This finding might suggest that the microbiome should be targeted during obesity programs.
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Could a change in diet revitalize children who suffer from unresolved fatigue?
Steenbruggen, TG, Hoekstra, SJ, van der Gaag, EJ
Nutrients. 2015;7(3):1965-77
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Up to 46% of children report suffering from fatigue, which can affect their ability to learn at school, mental health, immune system function and quality of sleep. Where there is no medical cause for the fatigue, a deficiency of micronutrients in the diet may be to blame. In this non-randomised controlled trial, a group of 98 children aged 2–18 years old with unexplained symptoms of fatigue was examined. Children in the intervention group were advised to follow a nutrient-rich diet for three months, consisting of green vegetables 5 times a week, beef 3 times a week, 200ml of whole milk daily and the use of full-fat butter. The control-group followed their normal diet. Children who followed the diet showed a significant decrease in the need to sleep. They slept better through the night and took fewer naps. General fatigue and cognitive fatigue also showed greater improvement in the intervention group, but the difference between the groups was not statistically significant. When analysing individual components of the diet, a significant improvement in cognitive fatigue symptoms was associated with eating green vegetables. A lower need to sleep was seen when whole milk was consumed almost daily. The authors suggest that nutritional advice is an elegant, and effective method for decreasing some symptoms of medically unresolved fatigue in children.
Abstract
Many children deal with fatigue for which no proper treatment can be given. A possible explanation for their fatigue is a micro deficiency of minerals and vitamins. In this non-randomized controlled trial, we clinically evaluated symptoms of fatigue in children for whom a nutrient-rich diet was advised. A group of 98 children (2-18 years old) with unexplained symptoms of fatigue was examined. The dietary modifications consisted of green vegetables, beef, whole milk and full-fat butter. Children in the intervention group were asked to follow the diet for three months, whereas the control-group followed their normal diet. The primary outcome was symptoms of fatigue, as determined by a PedsQL Multidimensional Fatigue Scale, and secondary outcomes were compliance with the diet and BMI. Children, who followed the diet showed a significant decrease in the need to sleep (CI 0.83; 14.86, p = 0.03). They slept better through the night and took fewer naps. When analyzing components of the advised diet separately, a significant larger decrease in cognitive fatigue symptoms was seen for eating green vegetables according to the diet guidelines (CI 2.27; 30.63, p = 0.024). Furthermore, a lower need to sleep was seen when whole milk was consumed almost daily (CI 0.02; 14.62, p = 0.049). Our study showed that nutritional advice is an elegant, and effective method for decreasing some symptoms of medically unresolved fatigue in children.
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Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity.
Hollon, J, Puppa, EL, Greenwald, B, Goldberg, E, Guerrerio, A, Fasano, A
Nutrients. 2015;7(3):1565-76
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Celiac disease (CD) and non-celiac gluten sensitivity (GS) are conditions caused by a reaction to gluten in the small intestines. When gluten is ingested, patients with CD produce an immune-mediated response in the intestinal mucosa whereas GS react symptomatically but do not produce an immune response. Due to this difference, it is thought that there may be a common defect in the intestinal barrier function in these two conditions. The aim of this study was to evaluate the response to gliadin exposure, both in terms of intestinal barrier function and immune cell secretion. Gliadin is a peptide in gluten that is responsible for the disassembly of intestinal tight junctions and therefore increased intestinal permeability. The study included intestinal explants from 23 patients. The findings of this study showed that gliadin exposure leads to a significant increase in intestinal permeability in all individuals. A deficiency in anti-inflammatory immune cells was also measured in patients with CD or GS, which is suggested to contribute to increased intestinal permeability.
Abstract
BACKGROUND Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). METHODS Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. RESULTS Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. CONCLUSIONS Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.
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Diet and faecal flora in the newborn: lactoferrin.
Balmer, SE, Scott, PH, Wharton, BA
Archives of disease in childhood. 1989;64(12):1685-90
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Previous studies have suggested that the gut microflora in newborns who are exclusively breastfed differs in comparison to bottle fed newborns. This study aimed to analyse the faecal flora of newborn babies for the effects of lactoferrin, which is present at high percentages in mother’s milk in comparison to the cow’s milk. Three different combinations of test formula milk based on bovine lactoferrin was given to newborn babies of mothers who had decided not to breastfeed. Samples of babies faeces were analysed to measure the concentration of lactoferrin and the faecal flora. The study found a significant difference in the faecal flora and concentration of the lactoferrin between the groups and suggested that the bovine lactoferrin was not bioactive in newborns. The only effect seen was in the group of babies who had the formula milk fortified with lactoferrin and iron together. More studies are needed on the basis of this result, suggesting that the addition of iron may have resulted in more significant colonisation of faecal flora.
Abstract
The faecal flora of breast fed babies differs from that of bottle fed babies. We have shown that the use of a whey predominant formula rather than a casein predominant one induced a faecal flora generally closer to that of breast fed babies but substantial differences remained. The whey proteins of breast milk include much more lactoferrin than is found in cows' milk. Observations both in animals and in vitro suggest that lactoferrin could be responsible for some of these differences between bottle and breast fed babies. This study was designed to determine the effects on faecal flora of the addition of bovine lactoferrin to the diet of bottle fed babies while holding other qualities of their diet constant. As lactoferrin is an iron binding protein three test formulas were used: (a) no added iron and no added lactoferrin (basic), (b) no iron but added lactoferrin (L), and (c) added iron and lactoferrin (LF). The addition of lactoferrin had little effect upon the faecal microflora and did not move the pattern of the faecal flora in the direction of the breast fed baby. The addition of iron to the formula had more effect on the faecal flora than did lactoferrin. At day 4 it encouraged Escherichia coli and discouraged staphylococcal faecal colonisation. At day 14 the addition of iron to the formula discouraged bifidobacteria. The reasons why bovine lactoferrin was ineffective in vivo in this study are discussed.