Between 1993 and 2005, an estimated 600 million children across the globe were diagnosed with anaemia, a disorder often caused by poor bioavailability of dietary iron resulting from malnutrition. Strategies to reduce mortality in children, especially those from low-income countries, are of the utmost importance. Iron supplementation is an obvious approach, but adverse side-effects from high-dose iron supplements have been widely reported. Lately, the addition of prebiotics and probiotics has proven to be effective for treating anaemia and is expected to treat many other diseases in the near future.
Anaemia: a global health problem
According to the WHO global database on anaemia, an estimated 600 million children across the globe between 6 months and 15 years of age were diagnosed with anaemia from 1993 to 2005 (1,2). Anaemia is a widespread blood disorder that is characterized by a decrease in red blood cells or haemoglobin in the blood. Having sufficient haemoglobin in the blood is an essential requirement for our well-being as it ensures the fundamental delivery of oxygen to tissues and organs in the body. It has been estimated that about half of worldwide anaemia cases are caused by iron deficiency, or in other words by not having enough iron in the blood. Other nutritional deficiencies such as folate, vitamin B12, riboflavin and vitamin C deficiency have also been shown to play a role in anaemia development (3). Inflammation, infection, and thalassemia (an inherited disease that accounts for loss of red blood cells) have also been tied to anaemia (4). Iron deficiency anaemia is a public health problem in both developing and industrialized countries. According to the WHO global database on anaemia, within a time frame of just over a decade it has affected more than 2 billion people worldwide and has contributed to 20% of all maternal deaths (1). It leads to impaired physical and cognitive development, increases the risk of morbidity in children, and reduces work productivity in adults (4). The high prevalence of infections and poor bioavailability of dietary iron, particularly in Sub-Saharan Africa, South and Southeast Asia continues to raise concern, and strategies to reduce mortality in children in these areas are of great urgency (2,5).
Malnutrition as a predominant factor
Half of all anaemic cases are caused by iron deficiency stemming from malnutrition (1). The World Health Organization (WHO) defines malnutrition as a deficiency, excess or imbalance in a person’s intake of energy and/or specific nutrients in relation to their daily requirements.
Approximately 5.6 million children die before their fifth birthday each year, with 80% of these deaths occurring in sub-Saharan Africa and Asia because of the lack of essential nutrients like iron in their diet (6). In these aforementioned areas, common risk factors also include exposure to pathogens, poor sanitary conditions, healthcare inaccessibility and poverty, which strongly contribute to the prevalence of malnutrition and iron-deficient anaemia. In developed countries, we often do not realize that we are not getting enough dietary iron, even though numerous studies have highlighted that pregnant women and non-pregnant women of childbearing age are the most vulnerable groups when it comes to anaemia, underlining the importance for women to ensure they get sufficient iron in their daily diet (7).
The dark side of iron
Iron supplementation has been the obvious go-to strategy for scientists and clinicians to ensure new-borns, young children and women, especially from low-income countries, acquire the recommended dose of iron. Anaemia rates in African countries are high since new-borns are typically given cereal or legume-based foods, which contain compounds that inhibit iron absorption (8). Recently, scientists developed an effective strategy to increase dietary iron intake without changing traditional diets. Here, micronutrient powders (MNPs) fortified with iron, vitamins and minerals can be easily added to home-cooked meals to feed new-borns and children. Nevertheless, it must be said that the safety of iron fortification trials has been questioned in the past, in particular concerning the high iron dosage used in these trials (8). In a 2003 study conducted in Zanzibar, an increased risk of malaria-associated morbidity and mortality in iron-sufficient children receiving iron supplements was described (9). Another trial in Tanzanian preschool children showed that oral iron supplements had increased the rate of hospitalizations and mortality (9), and similar cases had also been observed in a controlled trial with Ghanaian infants. Moreover, recent MNP trials conducted with infants reported increases in diarrhoea and respiratory tract infections (10). Seemingly, iron was doing more harm than good. Suffice to say, this was definitely not a ‘have your cake and eat it too situation’, and it raised the predominant question: how could we ensure sufficient iron intake in children without making them sick?
The surprising explanation
Occasionally in science, a hypothesis can lead to the unravelling of unexpected results, and this was definitely one of those cases. The need to understand what was going on was of great urgency. Researchers quickly identified the root cause of the problem, and surprisingly, it was happening in the gut (10). As previously highlighted in ‘Reshaping the gut is the secret to successful weight-loss’, having a balanced and diverse gut environment is crucial for the overall health and well-being of individuals. Ultimately, follow-up studies performed in 2017 by a handful of researchers indicated that less than 10% of supplemented iron from iron-fortified MNPs and iron supplements was being absorbed into the bloodstream of newborns. These supplements contained a high dose of iron (12.5 mg iron/day), indicating that up to 11.75 mg of unabsorbed iron was passing through the gut of these infants every day (10). To make matters worse, it has been shown that iron is also a very important requirement for the growth and colonisation of enteric bacteria like Salmonellaand pathogenic E.coli; the increase of pathogenic bacteria was in line with symptoms observed during previous trials i.e. diarrhoea, abdominal pain, and gut inflammation (10). Simply put, the unabsorbed iron was passing through the gut, feeding the progression of pathogenic bacteria which then drastically diminished healthy numbers of beneficial bacteria strains like Bifidobacteria and Lactobacilli in the gut. The results were hard to digest and quite unexpected: these MNPs containing high amounts of iron were just not working, and safer formulations of iron-containing supplements and MNPs had to be developed (8,10).
Prebiotics and probiotics: how they saved the day
In 2017, a team of Swiss scientists developed and tested a safer formulation of iron-fortified supplements which contained reduced levels of iron albeit ensuring maximum iron absorption (10). In addition, the supplementation of a prebiotic was proven effective to prevent the adverse effects of iron that were previously observed in the guts of Kenyan newborns during the initial studies. Prebiotics are a source of nondigestible fibers that can induce the selective growth of beneficial bacteria such as Bifidobacteria & Lactobacilli in the gut (11). Moreover, they have the ability to strengthen the intestinal flora and reduce the number of pathogenic bacteria and toxic metabolites in the gastrointestinal tract, making its recipients favorable candidates for iron-fortification therapies. While prebiotics are compounds that facilitate the growth of ‘good bacteria’ in the gut, probiotics, instead, are actual living microorganisms. Recently, probiotics have also gained vast media attention. They are a group of living bacteria and yeast that are naturally present in fermented foods and oral supplements (12). For example, naturally occurring probiotics are found in yogurt and fermented foods like sauerkraut and kimchi to name a few. For years, they have been widely used to promote human health, especially when it comes to maintaining a healthy digestive system, due to their ability to replenish ‘good bacteria’ during or after a course of antibiotics. Last year, a team of Serbian scientists also developed a probiotic formulation for iron-deficient anaemia, highlighting the importance for both prebiotics and probiotics in the human diet (13). Furthermore, probiotic oral supplements were recently approved in paediatric hospitals for the treatment of acute diarrhoea and antibiotic-associated diarrhoea (12).
A glimpse into the future
Interestingly, recent evidence has also shown that probiotics play a beneficial role in treating other diseases like irritable bowel syndrome (IBS) and necrotizing enterocolitis (14). Without a doubt, the rise in frequency of autoimmune and inflammatory bowel disease in developed and high-income countries cannot be disregarded (15). Our sedentary lifestyles, improved hygiene, and western diet have all played an active role in reshaping our gut profiles (14). Modern day diets contain too many processed foods rich in preservatives, sodium, and sugars, but not enough fiber-rich foods like fresh fruits and vegetables, all of which negatively shape our gut. So, despite the fact that the idea of ingesting live microorganisms may sound strange to you, just remember that our bodies contain more bacterial cells than human cells. We simply cannot live without bacteria. Ultimately, scientists still have a long way to go before they are able to identify all prebiotics and probiotics out there. Growing probiotic strains in laboratories has been exceptionally challenging, and researching their potential benefits even more so. Nonetheless, stay hopeful and trust that they are working endlessly to make our lives healthier!
One prebiotic at a time…
One probiotic at a time…
References:
- McLean E. et al. “Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005”, Public Health Nutr., 2009
- Scott SP. Et al. “The impact of anemia on child mortality: an updated review”, Nutrients, 2014
- Kassebaum N.J. et al. “A systematic analysis of global anemia burden from 1990 to 2010”, Blood, 2014
- De-Regil L.M. et al. “Intermittent iron supplementation for improving nutrition and development in children under 12 years of age”, Cochrane Database Syst. Rev., 2011
- Lackritz E.M. et al. “Longitudinal evaluation of severely anemic children in Kenya: The effect of transfusion on mortality and hematologic recovery”, AIDS, 1997
- Walson, JL and Berkley, JA., “The impact of malnutrition on childhood infections”, Curr Opin Infect Dis.,2018
- Worldwide prevalence of anaemia 1993–2005, WHO global database on anaemia, 2008
- Paganini D. and Zimmermann M.B. “The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review”, Am J Clin Nutr., 2017
- Sazawal S. et al. “Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: Community-based, randomised, placebo-controlled trial”, Lancet, 2006
- Paganini, D. et al. “Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants.”, Gut, 2017
- Carlson, J.L. et al. “Health Effects and Sources of Prebiotic Dietary Fiber”, Curr Dev Nutr., 2018
- Johnston BC., et al. “Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials.” CMAJ, 2006
- Korčok, DJ. et al. “Development of Probiotic Formulation for the Treatment of Iron Deficiency Anemia.”, Chem Pharm Bull (Tokyo), 2018
- Ritchie ML. and Romanuk TN. “A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases”, PLoS ONE, 2012
- Isolauri, E. “Probiotics in human disease”, Am J Clin Nutr., 2001
