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1.
The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature.
Reis, DJ, Ilardi, SS, Punt, SEW
PloS one. 2018;13(6):e0199041
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The microbiome-gut-brain axis in general and the possibility of altering the microbiome through administration of probiotics to support physical and mental health has received much attention in recent years. Here, a systematic review and meta-analysis were carried out to evaluate the clinical and preclinical evidence for the use of probiotics in anxiety. 22 preclinical (rodent) studies were included in the meta-analysis and showed an overall significant anxiolytic effect of probiotics in diseased, but not healthy, animals. Studies were heterogenous with regards to species and strains of probiotic used. Subgroup analysis showed that only Lactobacillus rhamnosus significantly reduced anxiety-like behaviour. 14 human studies were included in the meta-analysis and overall no anxiolytic effect was observed. Only three out of the 14 studies showed a positive effect (vs 12 out of the 22 animal studies), one of which used L. rhamnosus. Due to the small number of trials no subgroup analysis could be performed. Apart from the small number and heterogeneity of human studies, the authors discuss further possible reasons for the discrepancy between animal and human studies: • Dose: Dosages were typically 100 times higher (per kg) in animals than in humans. • Diseased vs healthy subjects: In animal studies, only those which investigated animals displaying anxiety related behaviour improved with probiotic administration. None of the human studies specifically recruited anxious individuals, eight of the studies included healthy subjects, the other six selected participants for other disorders, including four for irritable bowel syndrome. The authors conclude that more research into an anxiolytic effect of probiotics in humans is warranted, especially using L. rhamnosus, studying patients with anxiety, and using higher dosages and longer study duration.
Expert Review
Conflicts of interest:
None
Take Home Message:
- While preclinical animal studies suggest that probiotics may help reduce anxiety, such findings have not yet translated to clinical research in humans.
- Further investigation of probiotic treatment for clinically relevant anxiety is warranted, particularly with respect to the probiotic species L. rhamnosus.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This review highlights how important it is for future studies to focus on clinically anxious patients and also to consider exploring the effects of differing doses of probiotics in this population.
Clinical practice applications:
Anxiety disorders affect as many as 3 in 10 people at some point during their lifetime. On that basis, it would be great to have a viable non-pharmaceutical option to help with some of the symptoms.
Considerations for future research:
If the results from the pre-clinical studies can be corroborated in human populations, this could have widespread clinical implications.
Abstract
BACKGROUND Probiotics have generated intensive research interest in recent years as a novel mode of treatment for physical and mental illness. Nevertheless, the anxiolytic potential of probiotics remains unclear. The present systematic review and meta-analysis aimed to evaluate the clinical and preclinical (animal model) evidence regarding the effect of probiotic administration on anxiety. METHODS The PubMed, PsycINFO, and Web of Science databases were reviewed for preclinical and clinical studies that met the defined inclusion and exclusion criteria. The effects of probiotics on anxiety-like behavior and symptoms of anxiety were analyzed by meta-analyses. Separate subgroup analyses were conducted on diseased versus healthy animals, specific preclinical probiotic species, and clinical versus healthy human samples. RESULTS Data were extracted from 22 preclinical studies (743 animals) and 14 clinical studies (1527 individuals). Overall, probiotics reduced anxiety-like behavior in animals (Hedges' g = -0.47, 95% CI -0.77 --0.16, p = 0.004). Subgroup analyses revealed a significant reduction only among diseased animals. Probiotic species-level analyses identified only Lactobacillus (L.) rhamnosus as an anxiolytic species, but these analyses were broadly under-powered. Probiotics did not significantly reduce symptoms of anxiety in humans (Hedges' g = -0.12, 95% CI -0.29-0.05, p = 0.151), and did not differentially affect clinical and healthy human samples. CONCLUSIONS While preclinical (animal) studies suggest that probiotics may help reduce anxiety, such findings have not yet translated to clinical research in humans, perhaps due to the dearth of extant research with clinically anxious populations. Further investigation of probiotic treatment for clinically relevant anxiety is warranted, particularly with respect to the probiotic species L. rhamnosus.
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2.
Effect of a Protein Supplement on the Gut Microbiota of Endurance Athletes: A Randomized, Controlled, Double-Blind Pilot Study.
Moreno-Pérez, D, Bressa, C, Bailén, M, Hamed-Bousdar, S, Naclerio, F, Carmona, M, Pérez, M, González-Soltero, R, Montalvo-Lominchar, MG, Carabaña, C, et al
Nutrients. 2018;10(3)
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Protein supplements are popular among athletes to improve performance and increase muscle mass. However, their effect on other aspects of health is less well known. Dietary changes can affect gut microbiota balance, with beneficial or harmful consequences for the host. This small pilot study was performed on cross-country runners whose diets were complemented with a protein supplement (whey isolate and beef hydrolysate) or maltodextrin (control) for 10 weeks. Microbiota, water content, pH, ammonia, and short-chain fatty acids (SCFAs) were analysed in faecal samples, and oxidative stress markers were measured in blood plasma and urine. Faecal pH, water content, ammonia, and SCFA concentrations did not change, indicating that protein supplementation did not increase the presence of these metabolites of fermentation. Similarly, it had no impact on plasma or urine malondialdehyde levels. Protein supplementation did however increase the abundance of the Bacteroidetes phylum and decrease the presence of health-related taxa including Roseburia, Blautia, and Bifidobacterium longum. The authors concluded that long-term protein supplementation may have a negative impact on gut microbiota. Further research is needed to establish the impact of protein supplements on gut microbiota.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Long-term protein supplementation may have a negative impact on gut microbiota.
- Further research is needed to establish the impact of protein supplements on gut microbiota and whether there is a differential impact between protein from animal and plant sources.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This is a very interesting study that is relevant to athletic populations.
Clinical practice applications:
Potentially there is a role for probiotics / prebiotics when increasing protein intake (particularly of animal origin) to maintain microbiota diversity and prevent ensuing health complications.
Considerations for future research:
Further, larger scale, research is needed to understand whether the same effect of protein supplementation would be seen with plant-based proteins or whether this is unique to animal based protein supplementation. For example, is the hydrolysation of the proteins to account for the largest effect or could a whole food protein, i.e. not hydrolysed, elicit the same effects?
Also, is this effect seen in other sports, e.g. non-endurance. What about the effect under different conditions e.g. energy deficit vs. energy excess?
Abstract
Nutritional supplements are popular among athletes to improve performance and physical recovery. Protein supplements fulfill this function by improving performance and increasing muscle mass; however, their effect on other organs or systems is less well known. Diet alterations can induce gut microbiota imbalance, with beneficial or deleterious consequences for the host. To test this, we performed a randomized pilot study in cross-country runners whose diets were complemented with a protein supplement (whey isolate and beef hydrolysate) (n = 12) or maltodextrin (control) (n = 12) for 10 weeks. Microbiota, water content, pH, ammonia, and short-chain fatty acids (SCFAs) were analyzed in fecal samples, whereas malondialdehyde levels (oxidative stress marker) were determined in plasma and urine. Fecal pH, water content, ammonia, and SCFA concentrations did not change, indicating that protein supplementation did not increase the presence of these fermentation-derived metabolites. Similarly, it had no impact on plasma or urine malondialdehyde levels; however, it increased the abundance of the Bacteroidetes phylum and decreased the presence of health-related taxa including Roseburia, Blautia, and Bifidobacterium longum. Thus, long-term protein supplementation may have a negative impact on gut microbiota. Further research is needed to establish the impact of protein supplements on gut microbiota.
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Type-4 Resistant Starch in Substitution for Available Carbohydrate Reduces Postprandial Glycemic Response and Hunger in Acute, Randomized, Double-Blind, Controlled Study.
Stewart, ML, Wilcox, ML, Bell, M, Buggia, MA, Maki, KC
Nutrients. 2018;10(2)
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Resistant starch is a combination of dietary fibre and carbohydrate that ‘resists’ digestion in the small intestine and is fermented in the large intestine by gut bacteria. It is associated with a number of health benefits, particularly the management of blood glucose levels. This small double-blind, randomised controlled trail allocated 36 healthy individuals (mostly female, average age 46 and BMI 26) to eat either a low-fibre scone or a scone with added resistant starch in the form of acid-hydrolyzed and heat treated maize starch. The response of blood glucose and blood insulin levels were measured, as well as participants feeling of fullness and intestinal comfort after eating the scones. The scone with the added resistant starch had significantly lower blood glucose (43-45% lower) and blood insulin (35-40% lower) levels after eating the scone, when compared to those eating the low-fibre scone. They also reported feeling fuller for longer and had no particular digestive symptoms. Whilst this is a small study, Nutrition Practitioners may want to investigate dietary sources of resistant starch when working with clients to balance blood glucose and insulin levels.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Based on the findings of the Predict Study, it is highly probable that the same meal will elicit a different glycaemic response in individuals with different gut microbial compositions.
- The gut microbiota, therefore, needs to be taken into consideration when assessing glycaemic responses to a meal.
- Healthcare practitioners may like to consider the use of resistant starches as an additional tool to balance blood sugar responses to a meal.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Dietary modulation of the gut microbiota impacts human health. This paper discusses the effects of a man-made type of resistant starch on the glycaemic response to a meal. Based on the initial findings of the Predict Study, it is highly probably that the same meal will elicit a different glycaemic (and wider metabolic) response in individuals with different gut microbial compositions. So this paper confirms the need to take the gut microbiota into consideration when assessing glycaemic responses to a meal, both in research and in clinical practice.
Clinical practice applications:
Not all fibres are equal, and not all starches are equal. Type 4 resistant starch is a novel addition to the already known types 1, 2, and 3 and provides with clinicians with an additional tool to balance their patient's blood sugar response to a meal based on the effect of resistant starch on the gut microbiota.
Considerations for future research:
Resistant starches are known for their ability to affect gut microbiota composition and short-chain fatty acid concentrations which, in turn, have the ability to modulate immune and metabolic functions in the host, including cholesterol, fasting glucose, glycosylated haemoglobin, and pro-inflammatory markers. Further studies on glycaemic and wider metabolic responses to a meal must take into consideration the effect of resistant starches on gut microbial composition. Not doing so may be skewing scientific findings.
Abstract
Resistant starch (RS) is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. The primary aim of this randomized, double-blind, controlled study was to characterize the postprandial glucose response in healthy adults after consuming a high fiber scone containing a novel RS4 or a low fiber control scone without RS4. Secondary aims included assessment of postprandial insulin response, postprandial satiety, and gastrointestinal tolerance. The fiber scone significantly reduced postprandial glucose and insulin incremental areas under the curves (43-45% reduction, 35-40% reduction, respectively) and postprandial glucose and insulin maximum concentrations (8-10% and 22% reduction, respectively). The fiber scone significantly reduced hunger and desire to eat during the 180 min following consumption and yielded no gastrointestinal side effects compared with the control scone. The results from this study demonstrate that a ready-to-eat baked-good, such as a scone, can be formulated with RS4 replacing refined wheat flour to yield statistically significant and clinically meaningful reductions in blood glucose and insulin excursions. This is the first study to report increased satiety after short-term RS4 intake, which warrants further investigation in long-term feeding studies.
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4.
Cardiovascular Health Benefits of Specific Vegetable Types: A Narrative Review.
Blekkenhorst, LC, Sim, M, Bondonno, CP, Bondonno, NP, Ward, NC, Prince, RL, Devine, A, Lewis, JR, Hodgson, JM
Nutrients. 2018;10(5)
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Diets high in vegetables are linked with a lower incidence of chronic disease. Some vegetables may have much larger health benefits in comparison to others, and therefore dietary guidelines could be developed to include targeted advice on consuming specific types of vegetables with the greatest health benefits. This review of observational studies focused on the cardiovascular health benefits of specific vegetable types. Vegetables discussed in this review were grouped into the following types: leafy green, cruciferous, alliums, yellow-orange-red and legumes. These vegetables contain many nutrients and phytochemicals that have been proposed to have benefits for cardiovascular health. The authors looked at the results from nearly 100 observational studies. Most of the studies were carried out on older adults; some were focussed on a single gender (male or female), and some were mixed. Follow up periods in the studies ranged from 3 years to 28 years. Most of the studies relied on food frequency questionnaires (FFQs) to estimate vegetable consumption, and many did not define the size of a vegetable portion in grams. The percentage of studies demonstrating significant benefits of vegetable consumption on CVD ranged from 25% for legumes to 43% for leafy greens. The strongest beneficial effects on CVD risk were seen for leafy green and cruciferous vegetables. The authors concluded that the evidence in this review suggests intake of leafy green and cruciferous vegetables may confer strong cardiovascular health benefits. Increasing vegetable intake, with a focus on leafy green and cruciferous vegetables may provide the greatest benefits.
Expert Review
Conflicts of interest:
Educator for various organizations, such as Institute for Functional Medicine, American Academy for Anti-Aging Medicine
Take Home Message:
- Green leafy vegetables and cruciferous vegetables were found to most impactful for cardiovascular health.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This review highlights the role of specific types of vegetables based on color and nutrients for cardiovascular health benefit.
Clinical practice applications:
The authors investigated whether some vegetable types were more relevant for cardiovascular-related issues than others. Based on their review of the scientific literature, green, leafy vegetables and cruciferous vegetables were found to be most impactful.
Considerations for future research:
This review suggests that more research is needed to understand how certain plant foods, vegetables, and phytochemicals may be functionally important for certain organ systems.
Abstract
Adequate vegetable consumption is one of the cornerstones of a healthy diet. The recommendation to increase vegetable intake is part of most dietary guidelines. Despite widespread and long-running public health messages to increase vegetable intake, similar to other countries worldwide, less than 1 in 10 adult Australians manage to meet target advice. Dietary guidelines are predominantly based on studies linking diets high in vegetables with lower risk of chronic diseases. Identifying vegetables with the strongest health benefits and incorporating these into dietary recommendations may enhance public health initiatives around vegetable intake. These enhanced public health initiatives would be targeted at reducing the risk of chronic diseases, such as cardiovascular diseases (CVD). Specific vegetable types contain high levels of particular nutrients and phytochemicals linked with cardiovascular health benefits. However, it is not clear if increasing intake of these specific vegetable types will result in larger benefits on risk of chronic diseases. This review presents an overview of the evidence for the relationships of specific types of vegetables, including leafy green, cruciferous, allium, yellow-orange-red and legumes, with subclinical and clinical CVD outcomes in observational epidemiological studies.
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5.
Orthorexia nervosa: A behavioral complex or a psychological condition?
Strahler, J, Hermann, A, Walter, B, Stark, R
Journal of behavioral addictions. 2018;7(4):1143-1156
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Orthorexia nervosa (ON) is a condition characterised by an obsession for 'healthy eating' and avoidance of 'unhealthy food' with the violation of these rigid dietary rules being associated with shame, anxiety and distress. Whilst numerous studies have evidenced its existence, there is debate as to whether it is a behavioural phenomenon or a mental health condition like other eating disorders. Anecdotally, there are reports of physiological impacts (such as weight loss), psychological impacts (such as emotional instability) and social impacts (such as social isolation), which are similar to clinical eating disorders. This cross-sectional study aimed to explore whether ON is of clinical relevance, and if it can be distinguished from other mental health conditions. An online survey including orthorexic behaviours was completed by 713 subjects (80% female) aged 18-75 years. 4% showed significant orthorexic eating alongside lower levels of life satisfaction, wellbeing and higher levels of stress. Depression and obsessive compulsive tendencies were also found in 48% and 30% of those with ON respectively. The authors conclude that there are strong overlaps between ON, mental health conditions and disturbed eating behaviours, questioning whether it should be a mental health condition in its own right.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Orthorexia nervosa has been associated with other mental health conditions, including depression and obsessive compulsive disorder.
- Given this association, and the desire for individuals with the condition to seek validation of their orthorexic eating, healthcare practitioners should make appropriate referral to ensure the safety and wellbeing of these individuals.
- Debate continues on whether orthorexia nervosa should be viewed as a mental health condition and eating disorder or a behavioural phenomenon.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Orthorexia nervosa (ON) is gaining increasing interest in research and clinical practice. Whilst research has evidenced its existence, there is still an active debate of whether it should be viewed as a mental health condition and eating disorder in its own right. Diagnoses may be useful for some individuals to make sense of the symptoms they are experiencing, reduce their feelings of isolation and to help them take steps to get the right support needed to improve their health. In a similar way to other eating disorders, orthorexia nervosa has been associated with other mental health conditions including depression and obsessive compulsive disorder.
Clinical practice applications:
Whether defined as an eating disorder in its own right or not, orthorexia nervosa nevertheless is likely to have an impact on wellbeing, life satisfaction and stress. It is an important condition or behavioural phenomenon for practitioners to be aware of, particularly in nutrition fields that may attract those individuals looking for more information or endorsement of their desired orthorexic eating. Given its association with other mental health conditions, safety and appropriate referral should be made to ensure the wellbeing of these individuals.
Considerations for future research:
Research on orthorexia nervosa is considerably smaller compared to other eating disorder conditions and behaviours. Further empirical evidence is needed to support the debate as to whether it is an eating disorder in its own right, or a behavioural phenomenon, and further insight needed to establish its full impact on physical and psychological health.
Abstract
BACKGROUND AND AIMS Numerous studies have provided evidence for orthorexia nervosa (ON), an eating pattern characterized by an almost manic obsession for and fixation on healthy eating, to be of epidemiological relevance. However, there is scientific debate on whether it is merely a behavioral or lifestyle phenomenon as compared to a mental disorder. Aim of this cross-sectional study was to explore whether ON is of epidemiological and clinical relevance, and whether ON can be distinguished from other mental health disorders and healthy lifestyle features. METHODS An online survey including a measure of orthorexic behaviors [Duesseldorf Orthorexia Scale (DOS)], well-being and distress, eating behaviors, pathological eating, anxiety and depression, addictive behaviors, obsessive-compulsive symptoms, personality, and health behaviors was completed by 713 subjects (79.8% women, 18-75 years, median age: 25 years). RESULTS Twenty-seven subjects (3.8%, 21 women) showed significant orthorexic eating (DOS ≥ 30). ON cases reported lower well-being, lower satisfaction with life, and higher current stress levels than non-ON cases. The highest percentage of variation in ON was explained by pathological eating (R2 = .380), followed by eating style, Mediterranean diet, compulsive symptoms, and subjective social status. Importantly, ON provided hardly any additional predictive value for well-being when also considering pathological eating. DISCUSSION AND CONCLUSIONS Our data confirmed the epidemiological and clinical relevance of orthorexic behaviors, but the strong conceptual overlap with other mental health problems and pathological eating raise initial doubts as to whether ON is a distinct mental health disorder category. This co-occurrence, unique symptoms, and underlying processes need further exploration by comparing ON cases with patients with other mental disorders.
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Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial.
Lambert, MNT, Thybo, CB, Lykkeboe, S, Rasmussen, LM, Frette, X, Christensen, LP, Jeppesen, PB
The American journal of clinical nutrition. 2017;106(3):909-920
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Oestrogens play a vital role in maintaining bone health. The natural decline in oestrogen during menopause negatively impacts bone mineral density and increases the risk of osteoporosis and fractures. Standard interventions offered include calcium and vitamin D supplementation and hormone replacement therapy. As hormone replacement therapy is associated with increased cancer risk, there is a need to find effective treatments that display a suitable safety profile for long-term use. Isoflavones are compounds found in legume plants, many of which are dietary staples in some cultures. Isoflavones are phytoestrogens, substances that can selectively interact with human oestrogen receptors. Initial research on Isoflavones indicated that it reduces bone breakdown whilst showing protective effects for certain cancers. This randomized, double- blind, placebo-controlled trial compared the effectiveness of an lactic acid fermented, probiotic-rich isoflavone product from Red Clover (RCE) or a placebo, when given in addition to Calcium, Magnesium and Vitamin D (CMD) in postmenopausal women with osteopenia. Participants were monitored using blood tests assessing phytoestrogen activity and oestrogen metabolism, DXA scans to observe changes in bone structure and activity and dietary questionnaires. A total of 78 participants completed the study. The results showed that twice a day 60 mg isoflavones from RCE had a significant physiological impact on preventing bone loss associated with oestrogen deficiency, and was more effective in preserving bone density than CDM alone. The authors concluded that RCE was close to effectiveness to conventional bone-preserving treatments like hormone therapy but stood out due to its better safety profile and minimal side effects. Gut bacteria enhance the effectiveness of these isoflavones, which can be metabolised into compounds called equol. While before the study none of the participants could produce equol, in the end, half of the participants in the RCE group were able to produce equol, suggesting that the probiotic presence in the supplement positively influenced the participants' gut bacteria, creating favourable conditions. Additionally, RCE treatment led to favourable changes in urinary oestrogen metabolites associated with less carcinogenic oestrogen metabolism. In conclusion, the probiotic RCE, enhanced the effectiveness of CMD in preventing bone loss, whilst also increasing the ability to produce equol.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Fermented red clover extract, rich in bioavailable isoflavones with selective oestrogen receptor affinity and probiotics, combined with traditional supplementation (calcium, magnesium and vitamin D) improves bone mineral density and bone turnover compared to placebo in post menopausal women with osteopenia.
- Combining probiotics with isoflavones appears to enhance intestinal isoflavone uptake and isoflavone metabolism.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This was a well-constructed randomised, parallel-design, placebo-controlled, double-blind trial over 12 months. The primary aim was to determine the effectiveness of a novel fermented red clover extract (RCE) containing isoflavones and probiotics combined with traditional calcium/magnesium/vitamin D supplementation, in comparison with traditional calcium/magnesium/vitamin D supplementation alone on bone mineral density (BMD) in postmenopausal women with osteopenia.
Methods
- The trial followed the guidelines of the Declaration of Helsinki and received ethics approval.
- Inclusion criteria: female; >=1 year postmenopause; age 60-85; and bone T score of -1 to -2.25.
- Exclusion criteria: medical treatment for osteopenia or hormone replacement therapy within the past 3 months; diet rich in or supplementation with isoflavones; supplementation with Vitamin K; medical history of stipulated conditions.
- 85 participants were eligible and randomised to either the control or treatment group.
- Treatment group received 95 mL of RCE twice daily, containing 60 mg isoflavone aglycones and probiotics, plus 1040mg calcium, 487mg magnesium and 25μg Vitamin D daily (CMD/d). Control group received masked RCE placebo plus CMD/d.
Results
- The change in BMD (p=0.043) and T score (p=0.045) showed a statistically significant greater decrease in the lumbar spine, femoral neck and hip of the control group than the RCE treatment group after 12 months of treatment.
- A statistically significant reduction in one bone resorption marker was found in the RCE group compared to control (p=0.045). All other bone biomarkers failed to reach significance.
- Plasma isoflavone concentration was elevated in the RCE treatment group compared to control (p=0.0094).
- The concentration ratios of urinary oestrogen metabolites 2-OH:16αOH was significantly increased in the RCE group compared to control (p=0.026).
Conclusion
Fermented RCE with CMD/d slowed oestrogen-deficient BMD loss and improved one marker of bone turnover in postmenopausal osteopenic women. Combining RCE with CMD/d was found to be more effective in preserving bone density than CMD/d alone in this target group. Probiotics in the fermented RCE appear to enhance intestinal isoflavone uptake, metabolism, and therapeutic effect.
Clinical practice applications:
- Healthcare practitioners working with women in post-menopause with osteopenia could consider the addition of fermented RCE with CMD/d for improved bone mineral density and bone turnover over 12 months.
- Given the positive impact of RCE intake over 12 months on 2-OH:16αOH oestrogen metabolite ratios, healthcare practitioners could consider fermented RCE when HRT is not an available option in relation to cancer risk.
- Based on these results, Nutritional Therapists working with post-menopausal women with osteopenia can focus on dietary isoflavone intake and pre and probiotic foods to support BMD, alongside supplementary options.
Considerations for future research:
- Given the length of time taken in bone remodelling cycles, a clinical trial of more than 2 years would strengthen the evidence provided by DXA scan.
- All trial participants were normotensive and healthy weight. Future studies could include women with hypertension and obesity to determine effects of RCE on bone and blood pressure/lipid markers in this group.
- Controlled feeding studies to determine the dietary effects of isoflavones and pre and probiotic foods would provide additional information in this area.
- Other fermented RCE products should be trialled to replicate findings.
Abstract
Background: Female age-related estrogen deficiency increases the risk of osteoporosis, which can be effectively treated with the use of hormone replacement therapy. However, hormone replacement therapy is demonstrated to increase cancer risk. Bioavailable isoflavones with selective estrogen receptor affinity show potential to prevent and treat osteoporosis while minimizing or eliminating carcinogenic side effects.Objective: In this study, we sought to determine the beneficial effects of a bioavailable isoflavone and probiotic treatment against postmenopausal osteopenia.Design: We used a novel red clover extract (RCE) rich in isoflavone aglycones and probiotics to concomitantly promote uptake and a favorable intestinal bacterial profile to enhance isoflavone bioavailability. This was a 12-mo, double-blind, parallel design, placebo-controlled, randomized controlled trial of 78 postmenopausal osteopenic women supplemented with calcium (1200 mg/d), magnesium (550 mg/d), and calcitriol (25 μg/d) given either RCE (60 mg isoflavone aglycones/d and probiotics) or a masked placebo [control (CON)].Results: RCE significantly attenuated bone mineral density (BMD) loss at the L2-L4 lumbar spine vertebra (P < 0.05), femoral neck (P < 0.01), and trochanter (P < 0.01) compared with CON (-0.99% and -2.2%; -1.04% and -3.05%; and -0.67% and -2.79, respectively). Plasma concentrations of collagen type 1 cross-linked C-telopeptide was significantly decreased in the RCE group (P < 0.05) compared with CON (-9.40% and -6.76%, respectively). RCE significantly elevated the plasma isoflavone concentration (P < 0.05), the urinary 2-hydroxyestrone (2-OH) to 16α-hydroxyestrone (16α-OH) ratio (P < 0.05), and equol-producer status (P < 0.05) compared with CON. RCE had no significant effect on other bone turnover biomarkers. Self-reported diet and physical activity were consistent and differences were nonsignificant between groups throughout the study. RCE was well tolerated with no adverse events.Conclusions: Twice daily RCE intake over 1 y potently attenuated BMD loss caused by estrogen deficiency, improved bone turnover, promoted a favorable estrogen metabolite profile (2-OH:16α-OH), and stimulated equol production in postmenopausal women with osteopenia. RCE intake combined with supplementation (calcium, magnesium, and calcitriol) was more effective than supplementation alone. This trial was registered at clinicaltrials.gov as NCT02174666.
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7.
Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.
Kang, DW, Adams, JB, Gregory, AC, Borody, T, Chittick, L, Fasano, A, Khoruts, A, Geis, E, Maldonado, J, McDonough-Means, S, et al
Microbiome. 2017;5(1):10
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Children with autism spectrum disorders (ASD) often suffer gastrointestinal problems, such as constipation or diarrhea, the severity of which often correlate with ASD severity. This open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on GI and ASD symptoms of 18 ASD-diagnosed children. Treatment involved 2 weeks of antibiotic treatment and a bowel cleanse, followed by extended fecal microbiota transplant using a high initial dose and lower maintenance doses for 7-8 weeks. Results showed significant improvements in GI symptoms, which persisted 8 weeks after treatment ended. Bacterial diversity also increased. Behavioural ASD symptoms also improved significantly and lasted 8 weeks after treatment finished. This exploratory study suggests a promising approach to alter the gut microbiome in ASD subjects, improving GI and behavioural symptoms of ASD. Further clinical research is required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Fecal Microbiota Transfer Therapy demonstrates an effective clinical intervention in pediatric patients suffering with autistic spectrum disorder and associated gastrointestinal symptoms.
- Benefits of the therapy in this trail persisted even 2 months after treatment cessation.
- Future research on autistic spectrum disorder should address microbiota-gut-brain axis.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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X
C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The article describes an original clinical protocol in which microbiota transfer was used to ameliorate gastrointestinal (GI) and autism symptoms in pediatric patients. Common occurrence of GI pathology in patients affected by autistic spectrum disorder (ASD), poses a clinical challenge, since there is no standardised specific therapy. In light of recent insights on the importance of microbiota-gut-brain axis in health and disease, microbiota emerges as a salient treatment target in the aforementioned population.
Clinical practice applications:
Fecal microbiota transfer therapy (MTT) applied by the protocol described in the article demonstrates a longer-term effective clinical intervention in pediatric patients suffering from ASD and concomitant GI symptoms. Benefits of the therapy persisted even two months after actual treatment cessation, a highly important feature considering ASD.
Considerations for future research:
This modality could complement current treatments used for ASD-related symptomatology, but requires further validation through additional clinical experiments. The procedure also supports the efforts to focus more research on the role of microbiota in ASD pathophysiology. Further basic and clinical investigations on ASD should include addressing microbiota-gut-brain axis whenever possible, if not always.
Abstract
BACKGROUND Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. RESULTS MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). CONCLUSIONS This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. TRIAL REGISTRATION This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
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8.
Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial.
Most, J, Timmers, S, Warnke, I, Jocken, JW, van Boekschoten, M, de Groot, P, Bendik, I, Schrauwen, P, Goossens, GH, Blaak, EE
The American journal of clinical nutrition. 2016;104(1):215-27
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Plain language summary
The prevalence of obesity and related chronic diseases is continuously increasing. Insulin resistance is a major risk factor for the progression of obesity toward chronic metabolic diseases, including cardiovascular disease and type 2 diabetes. Polyphenols were identified as dietary ingredients with antioxidant properties decades ago. Epigallocatechin-3-gallate (EGCG), which is most abundant in green tea, and resveratrol (RS), which is present in grape skins, have been implicated in the prevention of body weight gain and improvements in markers of insulin sensitivity in human and animal studies. The aim of this randomised control study was to investigate the longer-term effect of EGCG and RES (EGCG+RES) supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity. 38 overweight and obese men and women received supplementation with either EGCG+RES (282 and 80 mg/d, respectively) or a placebo for 12 weeks. Before and after the intervention, oxidative capacity, lipid metabolism and insulin sensitivity were measured. EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass decreased after the intervention compared with placebo. EGCG+RES supplementation significantly increased oxidative capacity in muscle fibres. Fat oxidation and energy expenditure were not significantly affected by EGCG+RES. Finally, EGCG+RES had no effect on insulin-stimulated glucose disposal, suppression of endogenous glucose production, or lipolysis. The authors concluded that 12 weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo, and this may improve physical condition and play a role in the prevention of weight gain and worsening of insulin resistance in the long term.
Expert Review
Conflicts of interest:
None
Take Home Message:
- 12 wks of EGCG+RES intake increased skeletal muscle oxidative capacity as well as upregulating mitochondrial pathways, which may translate into an improved metabolic risk profile over time because greater mitochondrial capacity has been associated with higher insulin sensitivity in other studies
- The fat oxidation alterations in those taking the active ingredients vs. the placebo group suggests that this intervention could lead to metabolic adaptation towards lipids instead of CHOs as a fuel source, over time.
- EGCG+RES intake attenuated the increase in plasma triacylglycerol levels during the HFMM test, while the levels were significantly increased in the placebo group after 12 wks. This suggests that the intervention may provide positive support for individuals with high triacylglcerol (triglyceride) levels
- The ratio of total cholesterol to HDL cholesterol tended to decrease after EGCG+RES supplementation but not after placebo. Increased total & HDL cholesterol marker for myocardial infarction risk, so this intervention could help with persons who have disordered cholesterol values, and perhaps contribute to reducing their MI risk over time.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- This randomised controlled trial investigated the effect of 12-wk supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and insulin sensitivity.
- 38 overweight and obese subjects (active ingredient cohort n = 18; placebo n = 20) received 282 mg/d EGCG and 80 mg/d resveratrol; one capsule of each was taken at breakfast and dinner. Subjects were medically screened 10 times in total, including: 3 times before starting supplementation, 3 times during the supplementation period, and 3 in the last week of supplementation.
- EGCG capsules contained 94% epigallocatechin-3-gallate (141 mg/capsule) and resveratrol capsules contained 20% trans-resveratrol (40 mg trans-resveratrol in Polygonum cuspidatum extract/capsule).
- Medical screening included skeletal muscle biopsies (Vastus lateralis), with various tests done to measure oxidative capacity, X-ray absorptionmetry, a high-fat mixed meal (HFMM) test, and an insulin test via hyperinsulinemic-euglycemic clamp; meal intake before screening was standardised.
- Blood probes were also taken, and subjects completed food records; exact kcals per macronutrient were calculated.
Clinical practice applications:
The results of the study, which relate to clinical practice, highlight:
- 12 weeks of ECGC+RES supplementation increased mitochondrial capacity.
- EGCG+RES increased skeletal muscle oxidative capacity as well as protein expression of OxPhos complexes in skeletal muscle.
- EGCG+RES supplementation significantly affected fasting substrate oxidation, whereas fat oxidation declined in the placebo group; this suggests that it could help to improve fat metabolism.
- 12 weeks of ECGC+RES supplementation preserved fasting and postprandial fat oxidation compared with placebo.
- Plasma triacylglycerol levels were not significantly increased in the EGCG+RES cohort on being given an HFMM test after 12 wks, whereas they went up in the placebo group, indicating that this intervention preserved fasting and post-prandial fat oxidation.
- EGCG+RES group tended to decrease visceral adipose tissue mass by ~11% vs. placebo,
- These findings suggest that combined ECGC+RES supplementation might support mitochondrial function and weight loss/insulin sensitivity over a longer period of time
Considerations for future research:
- The EGCG+RES supplementation had no effect on postprandial glucose, insulin and FFA concentrations or local interstitial glucose and glycerol concentrations. Altering the study parameters in the future might identify changes of these markers.
- There was a tendency toward visceral adipose tissue mass decrease that was not considered significant, but altering dosage and length of time of a similar study might result in a more notable outcome related to weight loss, which was a targeted endpoint
- The combined supplements were not found to affect energy expenditure, contrary to a previous study by the same team, which was for a much shorter time period. It would be interesting to identify why this was.
- Complex and numerous gene set enrichment analyses were performed indicating that the most upregulated pathways after EGCG+RES supplementation were related to the Krebs cycle and electron transport chain, whereas pathways related to CHO metabolism were upregulated in the placebo group. This was taken to indicate that the increased mitochondrial capacity after EGCG +RES supplementation is accompanied by changes at the transcriptional and translational levels; further follow-up of this would be useful to know what clinical impact this has longer term
Abstract
BACKGROUND The obese insulin-resistant state is characterized by impairments in lipid metabolism. We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal (HFMM) test in men. OBJECTIVE The present study aimed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity. DESIGN In this randomized double-blind study, 38 overweight and obese subjects [18 men; aged 38 ± 2 y; body mass index (kg/m(2)): 29.7 ± 0.5] received either EGCG+RES (282 and 80 mg/d, respectively) or placebo for 12 wk. Before and after the intervention, oxidative capacity and gene expression were assessed in skeletal muscle. Fasting and postprandial (HFMM) lipid metabolism was assessed by using indirect calorimetry, blood sampling, and microdialysis. Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-(2)H2]-glucose infusion. RESULTS EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass tended to decrease after the intervention compared with placebo (P-time × treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers (P-time × treatment < 0.05, P-EGCG+RES < 0.05). Moreover, EGCG+RES reduced fasting (P-time × treatment = 0.03) and postprandial respiratory quotient (P-time × treatment = 0.01) compared with placebo. Fasting and postprandial fat oxidation was not significantly affected by EGCG+RES (P-EGCG+RES = 0.46 and 0.38, respectively) but declined after placebo (P-placebo = 0.05 and 0.03, respectively). Energy expenditure was not altered (P-time × treatment = 0.96). Furthermore, EGCG+RES supplementation attenuated the increase in plasma triacylglycerol concentrations during the HFMM test that was observed after placebo (P-time × treatment = 0.04, P-placebo = 0.01). Finally, EGCG+RES had no effect on insulin-stimulated glucose disposal, suppression of endogenous glucose production, or lipolysis. CONCLUSION Twelve weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects. This trial was registered at clinicaltrials.gov as NCT02381145.
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9.
Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial.
Akkasheh, G, Kashani-Poor, Z, Tajabadi-Ebrahimi, M, Jafari, P, Akbari, H, Taghizadeh, M, Memarzadeh, MR, Asemi, Z, Esmaillzadeh, A
Nutrition (Burbank, Los Angeles County, Calif.). 2016;32(3):315-20
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Probiotic supplementation in those with major depressive disorder decreased outcome measures of depression over a short period when compared with placebo.
- Further positive impacts were seen in the treatment arm of the study, with decreased serum insulin levels, decreased serum CRP concentration and increased total glutathione compared to placebo.
- Healthcare practitioners working with depression may wish to consider the role of microbiome diversity in symptom reduction.
- Longer, larger trials of probiotics impact on depression are needed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Here we have a study examining the effects of probiotic supplementation on symptoms of depression, metabolic profiles, C-reactive protein and biomarkers of oxidative stress among patients with major depressive disorder (MDD). This randomised double-blind placebo-controlled clinical trial was conducted over 8 weeks in Iran among 40 patients aged 20-55 with a diagnosis of MDD. Probiotic capsules containing Lactobacilus acidophilus, Lactobacillus casei and Bifidobacterium bifidum were given to the probiotic group and considered alongside a placebo group. At the end of the study, the probiotic group had significantly decreased outcome measures of depression, decreased serum insulin levels, decreased serum CRP concentration and increased total glutathione compared to the placebo group.
Clinical practice applications:
While this study offers promise, there are limitations, including the small sample size and the study length. The study suggests that further parameters would need to be considered, such as lipid profiles, to lengthen the duration of probiotic supplementation. These results suggest that a longer study period and investigation is certainly warranted however, and more research in this area may help us to understand the mechanisms by which depression outcome was improved.
Considerations for future research:
This study not only suggests that probiotic supplementation may be beneficial for individuals experiencing depression but gives us some insight into how the microflora of the intestines may affect functioning beyond the gut in this instance, metabolic status, biomarkers of inflammation and oxidative stress, all of which have been attributed to the aetiology of depression in research over the years.
Abstract
OBJECTIVE We are aware of no study examining the effects of probiotic supplementation on symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). The present study was designed to determine the effects of probiotic intake on symptoms of depression and metabolic status in patients with MDD. METHODS This randomized, double-blind, placebo-controlled clinical trial included 40 patients with a diagnosis of MDD based on DSM-IV criteria whose age ranged between 20 and 55 y. Patients were randomly allocated into two groups to receive either probiotic supplements (n = 20) or placebo (n = 20) for 8 wk. Probiotic capsule consisted of three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 10(9) CFU/g), Lactobacillus casei (2 × 10(9) CFU/g), and Bifidobacterium bifidum (2 × 10(9) CFU/g). Fasting blood samples were taken at the beginning and end of the trial to quantify the relevant variables. All participants provided three dietary records (two weekdays and one weekend) and three physical activity records during the intervention. RESULTS Dietary intake of study participants was not significantly different between the two groups. After 8 wk of intervention, patients who received probiotic supplements had significantly decreased Beck Depression Inventory total scores (-5.7 ± 6.4 vs. -1.5 ± 4.8, P = 0.001) compared with the placebo. In addition, significant decreases in serum insulin levels (-2.3 ± 4.1 vs. 2.6 ± 9.3 μIU/mL, P = 0.03), homeostasis model assessment of insulin resistance (-0.6 ± 1.2 vs. 0.6 ± 2.1, P = 0.03), and serum hs-CRP concentrations (-1138.7 ± 2274.9 vs. 188.4 ± 1455.5 ng/mL, P = 0.03) were observed after the probiotic supplementation compared with the placebo. Additionally, taking probiotics resulted in a significant rise in plasma total glutathione levels (1.8 ± 83.1 vs. -106.8 ± 190.7 μmol/L, P = 0.02) compared with the placebo. We did not find any significant change in fasting plasma glucose, homeostatic model assessment of beta cell function, quantitative insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels. CONCLUSIONS Probiotic administration in patients with MDD for 8 wk had beneficial effects on Beck Depression Inventory, insulin, homeostasis model assessment of insulin resistance, hs-CRP concentrations, and glutathione concentrations, but did not influence fasting plasma glucose, homeostatic model assessment of beta cell function, quantitative insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels.
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10.
Glycoconjugates in human milk: protecting infants from disease.
Peterson, R, Cheah, WY, Grinyer, J, Packer, N
Glycobiology. 2013;23(12):1425-38
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Expert Review
Conflicts of interest:
None
Take Home Message:
- This study looks at the role of carbohydrates in human milk and concludes that they play a health protective role in infants.
- Infant formula preparations could be enhanced to include free oligosaccharides, glycoproteins and glycolipids and offer protection to babies against disease in early months of life.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The protective properties of human milk have been, until recently, almost exclusively attributed to maternal antibodies within the milk. Moreover, this has become widely accepted conventional wisdom. However, more recent studies have shown that carbohydrates present in human milk, either as free oligosaccharides or bound to proteins or lipids (forming glycoproteins and glycolipids, respectively), also protect infants against disease. In this paper the authors make an exhaustive review of the human milk glycoproteins and glycolipids which play protective role against infections together with their mode of action. In addition to the protective role of human milk glycoproteins and glycolipids, the authors also discuss the protective role of bovine milk glycoproteins and glycolipids, since infant formulas based on cow's milk are commonly used as a replacement for mother's milk.
Clinical practice applications:
The information presented in this review has practical application for improving infant formula preparations. The findings reviewed in this paper together with future research in this area could lead to the development of enhanced infant formulas, enriched with recombinant human milk glycoproteins and glycolipids which would provide better protection for babies against many diseases.
Considerations for future research:
It is well known that glycans (complex sugars that are often attached to proteins and lipids) have numerous roles in various physiological processes. The ability of glycans to inhibit binding of different pathogens to host cell ligands, as it was shown for glycans present in human milk, represent just one more example of important roles played by glycans. Further research is needed to understand the mechanisms by which milk glycans ensure protection against different pathogens.
Abstract
Breastfeeding is known to have many health benefits for a newborn. Not only does human milk provide an excellent source of nutrition, it also contains components that protect against infection from a wide range of pathogens. Some of the protective properties of human milk can be attributed to the immunoglobulins. Yet, there is another level of defense provided by the "sweet" protective agents that human milk contains, including free oligosaccharides, glycoproteins and glycolipids. Sugar epitopes in human milk are similar to the glycan receptors that serve as pathogen adhesion sites in the human gastrointestinal tract and other epithelial cell surfaces; hence, the milk glycans can competitively bind to and remove the disease-causing microorganisms before they cause infection. The protective value of free oligosaccharides in human milk has been well researched and documented. Human milk glycoconjugates have received less attention but appear to play an equally important role. Here, we bring together the breadth of research that has focused on the protective mechanisms of human milk glycoconjugates, with a particular focus on the glycan moieties that may play a role in disease prevention. In addition, human milk glycoconjugates are compared with bovine milk glycoconjugates in terms of their health benefits for the human infant.