Contributions from nature and science in the treatment of digestive discomfort


No matter what complicates a baby’s digestion, nature provides a number of compounds that provide gentle support. Integrating them into the infant’s nutritional plan according to scientifically tested methods contributes greatly to a child's digestive comfort and well-being.

Bottle with peppermint oil and peppermint leaves

Herbal extracts


Many treatment options for gastrointestinal disorders are available, but they are either effective and yield potential undesirable effects, or are safe but less effective. Parents are drawn to complementary and alternative medicine (CAM) such as herbal extracts because of the assumption that their natural sources lead to safer therapies (Pike et al, 2013). 
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Probiotics


Probiotics are natural live microorganisms that are beneficial for the host’s health. They are frequently employed in the treatment of gastrointestinal disorders and may also be beneficial for the development of babies’ and toddlers’ digestive systems. Scientific findings demonstrate that probiotics alleviate symptoms of acute gastroenteritis, inflammatory bowel disease, diarrhoea, infantile colic, constipation, and regurgitation
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Probiotic bacteria
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Prebiotics


For acknowledgement of a substrate as prebiotic three criteria need to be met. The most challenging of these is the demonstration of a health benefit (or reduction of disease) in the host mediated by some but not all microorganisms that ferment the substrate. Health benefits  of dietary prebiotic (candidates) are direct through binding of pathogens (decoy effect) or indirect and associated with short-chain fatty acids as product of selective fermentation. Human milk oligosaccharide isoforms, galacto- and fructooligosaccharides, and lipophilic substances are under investigation for their classification as prebiotics.
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Carbohydrate-, fat-, and protein-related helpers


Science shows that the three main natural groups of energy-providing nutrients – carbohydrates, fats, and proteins – are digested in very different ways. Consequently, modifications in a baby’s nutrition are an effective way to naturally support its healthy digestion. Nowadays, a number of scientifically tested carbohydrate-, fat-, and protein-related solutions exist. 
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It is obvious that plenty of natural helpers related to infant digestion exist. In order to get a better overview of the helpers, their respective effects, and their (combined) usage, we have prepared a useful table based on our research outcomes: 
Summary of natural helpers 

  • Herbal extracts


    Around 52% of children in Europe use complementary and alternative medicine (CAM) and its popularity continues to grow, leading to an increasing range of new herbal extracts entering the market (Anheyer et al, 2017). Around 52% of childr  (Anheyer et al, 2017). Accordingly, many herbal preparations have been used and evaluated in the treatment of functional gastrointestinal disorders (FGIDs) in infants and children. 

    Individual extracts and combined approaches have both been evaluated in several different disorders including diarrhoea, dehydration due to gastroenteritis, infantile colic, irritable bowel syndrome, functional abdominal pain, and constipation (Anheyer et al, 2017). A combination of apple pectin and chamomile (Matricaria chamomilla) is shown to result in a significant reduction in the duration of diarrhoea and also a reduction in stool frequency (Becker et al, 2006; De la Motte et al, 1997). A tormentil root extract (Potentilla tormentilla) was also evaluated in treating children with diarrhoea caused by a rotavirus infection showing a significant decrease in the duration of diarrhoea, abnormal stool, stool output and hospitalisation (Subbotina et al, 2003). 

    The management of infantile colic has been evaluated mainly using fennel (Foeniculum vulgare) and chamomile (Matricaria chamomilla). A tea preparation based on fennel extract is shown to significantly reduce crying time when compared to usual care (Arikan et al, 2008). A herbal preparation based on several plant extracts (Matricaria chamomilla, Verbena officinalis, Glycyrrhiza glabra, Foeniculum, and Melissa officinalis) is able to reduce colic and colic-based symptoms in comparison to placebo tea preparations (Weizman et al, 1993). A recent clinical study evaluates a preparation of Matricariae chamomilla L., Melissa officinalis L. and tyndallised Lactobacillus acidophilus in comparison to conventional treatments such as administration of Lactobacillus reuteri and simethicone. This herbal preparation shows positive results, reducing the daily crying time of infants (a relevant clinical indicator to evaluate infantile colic), and proves to be significantly more effective than simethicone (Martinelli et al, 2016).

    Another study investigates the use of peppermint oil (Mentha piperita) in treating functional abdominal pain. Peppermint-oil capsules are evaluated against probiotic and folic acid tablets. The study shows that peppermint oil significantly reduces the duration, frequency, and severity of pain without showing any significant side-effects (Asgarshirazi et al, 2015).

    Ginger extract (Zingiber officinale) is another herbal extract that should be evaluated in children. Ginger root extract has traditionally been used to treat reflux symptoms and dyspepsia. Several studies with adult participants show potential benefits of this extract, including improved gastric emptying and gastroduodenal motility in both fasting and fed states. Other properties have also been attributed to this extract such as spasmogenic properties and antiplatelet effects (Yeh et al, 2014). Although no trials have been carried out in terms of its safety in paediatrics, ginger extract has been evaluated in pregnant women showing no risk to foetal development and is therefore likely to be safe (Yeh and Golianu, 2014). Hence, if made palatable and formulated in a child-friendly way, ginger extract could be another herbal-based solution to address gastrointestinal disorders in the near future.

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  • Probiotics


    Definition

    The human body and intestinal microbiota have an intimate and bidirectional interaction that can have both positive and negative influences on human health. These interactions between gut microbiota and the host have been shown to influence systemic immunity, defense against pathogens, intestinal motility, barrier functions, and even growth and development (Ringel et al, 2012).

    Probiotics are live organisms, which – when administered in adequate quantities – provide health benefits to the host (Guarner et al, 2017). Management and treatment of gastrointestinal disorders are among the main reasons for the usage of probiotic-based formulations and products. This is because probiotics have been linked with several gastrointestinal functions, including intestinal barrier protection, immunological and antibacterial functions, intestinal motility, and sensation effects (McFarland, 2010; Ohland and Macnaughton, 2010).

    Scientific research 

    Due to their dynamic interaction and range of positive effects, probiotics have been thoroughly evaluated in the management of several functional gastrointestinal disorders (FGIDs) including diarrhoea (acute, infectious or related to antibiotics), irritable bowel syndrome (IBS), functional constipation, and even infantile colic and colic-associated symptoms (Ringel et al, 2012; Corpino, 2017). At the same time, several commercially available solutions are based on probiotic strains, which include Lactobacillus (acidophilus, rhamnosus, casei, or reuteri), Bifidobacterium (lactis, infantis, breve or longum) and Bacillus (coagulans) species (Ringel et al, 2012). Lactobacillus and Bifidobacterium species are amongst the most commonly-used probiotics.

    Several scientific and clinical studies have been developed to test the efficacy of probiotic strains to prevent and/or manage FGIDs. In 2014, a working group was established by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) to research probiotics. They recommend using Lactobacillus rhamnosus and Saccharomyces boulardii to treat acute gastroenteritis because it results in a probiotic-related decrease in the duration and severity of symptoms in children (Szajewska et al, 2014). Constipation has been assessed using probiotic approaches, too. A systematic review by Wojtyniak and Szajewska published in 2017, summarises the effectiveness of probiotic strains in treating functional constipation. It includes treatment success, defecation frequency, faecal incontinence and abdominal pain (Wojtyniak and Szajewska, 2017). This review identifies the following species as assisting in the management of functional constipation: Lactobacillus (casei, rhamnosus, reuteri) and Bifidobacterium (lactis, longum). IBS  has also been examined using Lactobacillus rhamnosus, and results indicate increased treatment success, reducing frequency and severity of abdominal pain (Horvath et al, 2011; Corpino, 2017).

    Although presenting an unclear pathogenesis and possible multifactorial cause, infantile colic has also been approached using probiotic-based solutions. Systematic reviews and meta-analysis conclude that Lactobacillus reuteri strains have a role in treating, but not in preventing, infantile colic, and – by reducing infant crying time – offer an alternative solution to traditional pharmacological options (Benninga et al, 2016; Corpino, 2017). In addition, Lactobacillus reuteri has also been used in the management and treatment of functional abdominal pain, infant regurgitation and constipation (Orel, 2013). 

    Recent strategies also include the use of inactivated probiotics due to their inherent stability and viability advantages. Tyndallised Lactobacillus acidophilus was evaluated in combination with herbal extracts (Matricariae chamomilla L., Melissa officinalis L.) in the treatment of infantile colic. The combination reduces daily crying time of infants and is more effective when compared to Lactobacillus reuteri and simethicone (Martinelli et al, 2016).

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  • Prebiotics


    The International Association for Probiotics and Prebiotics (ISAPP) defines a prebiotic as "a substrate that is selectively utilized by host microorganisms conferring a health benefit"(Gibson et al. 2017). Accordingly, prebiotics are not limited to carbohydrates nor is their effect limited to the gastrointestinal tract. Also the nasal or oral cavities, vagina, skin, bone health, brain function or the cardiovascular are seen as organ systems beneficially affected by prebiotics (Gibson et al. 2017).

    A prebiotic substrate has to reach the localised microbiota intact, is specifically selected as food source by certain microbiota species, and the health benefit (enhancing health or reducing disease symptoms) is mediated through specific – not all – resident microbiota species (Gibson et al. 2017; Krumbeck et al. 2016). A prebiotic that encourages growth of Bifidobacterium subspecies is called "bifidogenic" i.e. it exerts "bifidogenic effects" or supports "bifidogenesis" which is positive because the growing bifidobacteria population is considered a sign of intestinal health (Ríos-Covián et al. 2016; Roberfroid et al. 2010). Together with Lactobacillus subspecies, these were the first intestinal microbiota species associated with health benefits. With progress in analytical methods, other possibly beneficial microbiota species are being identified (Hutkins et al. 2016).

    Potential prebiotic-associated health benefits include but are not limited to the reduction of infantile colic, risk for atopic disease, infection, mucosal inflammation, or gas production and stimulation of peristaltic and softer stool consistency leading to increased defaecation frequency (Krumbeck et al. 2016). These health benefits are most likely mediated by prebiotic modes of action that include

    • the increased growth or activity of beneficial microbiota species,
    • reduction or inhibition of pathogens,
    • decreased bacterial gut barrier translocation via promotion of colonic mucin production
    • stimulation of the immune system and regulation of signalling pathways,
    • regulation of plasma lipid concentrations,
    • increasing sensitivity to insulin and other hormones, and
    • changes in bioavailability of substances affecting other organs beneficially such as brain function and cognition or bone mineralisation (Gibson et al. 2017; Krumbeck et al. 2016).

    Prebiotics stimulate growth or activity of bacteria that produce short-chain fatty acids (SCFA) – acetate, butyrate, propionate and other volatile variants – and a subsequent reduction in intestinal pH. The reduced pH creates a difficult growth environment for many pathogens. Thus, the lowered pH caused by the fermentation products SCFA from certain bacteria species that use the prebiotic substrate protects against infections (Gibson et al. 2017; Ríos-Covián et al. 2016). In addition, butyrate serves as preferred fuel for many intestinal cells, promotes barrier function, and – together with acetate - negatively affects inflammation (Krumbeck et al. 2016).

    Pathogen inhibition can also occur by binding of the prebiotic substrate to the pathogen or receptor sites and thus preventing "docking" to cell surfaces. This is called "decoy effect" by which for example certain human milk oligosaccharide (HMO) isoforms bind to potential pathogens (Gibson et al. 2017).

    Some bacteria genera induced by prebiotics substrates modulate the expression of pro- and anti-inflammatory cytokines and thus regulate gut inflammation. Bifidobacterium subspecies increase expression of secretory immunoglobulin A, a key player in the complement immune system (Krumbeck et al. 2016).

    Establishing such a health benefit is difficult but the ISAPP suggests that a study in the target population should demonstrate a change in health markers or symptoms mediated by specific microbiota populations that are affected by the prebiotic substrate (Gibson et al. 2017). The most extensive body of evidence has accumulated on oligosaccharides (OS) such as inulin and oligofructose (from inulin), fructooligosaccharides (FOS) and galactooligosaccharides (GOS). These indigestible carbohydrates are bifidogenic (Hutkins et al. 2016). The investigation of their health benefits is ongoing. Other prebiotic candidates are natural and synthetic human milk oligosaccharide isoforms, bovine milk oligosaccharides, some poly-unsaturated fatty acids (PUFA), conjugated linoleic acid (CLA), lactulose, resistant starch, pectin, bile acids, and plant polyphenols (Gibson et al. 2017; Hutkins et al. 2016).


    Gibson et al. 2017. Nat Rev Gastroenterol Hepatol 14(8), 491–502

     

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  • Carbohydrate-, fat-, and protein-related helpers


    Carbohydrate-related helpers 

    Lactose (milk sugar), which is the main carbohydrate in standard baby milk, is hydrolysed – or in other words, enzymatically broken down – by lactase.  Although milk sugar is naturally found in breast milk, too, it is common that lactase defiency may occur in children at least transiently  (Vandenplas et al, 2013b). Consequently, lactose-reduced formulas are associated with a decrease in the number of crying episodes per week and total crying time (which are both indicators of colic)  (Vandenplas et al, 2013b). In addition, studies of hospitalised children show  that lactose-free feeds decrease the duration of diarrhoea (Guarino et al, 2014).

    A special subgroup of carbohydrates is fibre. Due to its indigestibility, it reacts primarily in the gastrointestinal tract itself, which is a useful characteristic for plant-based solutions to normalise a baby’s digestion. For example, early re-alimentation with baby milk rich in banana fibre shortens the duration of diarrhoea, dehydration, fever, abdominal pains, vomiting, prevents the occurrence of pathological additives in the stool, and counteracts body mass deficiencies (Czerwionka-Szaflarska et al, 2011).
    Related to reflux and regurgitation, another natural solution is locust bean gum, also known as carob bean gum. It contains the functional carbohydrate carubin. At lower gastric pH levels, it leads to thickening and increased viscosity of baby milk, and in this way presents a safe and well-tolerated – as well as clinically proven – solution to reduce reflux and regurgitation (Meunier et al, 2014, Wenzl et al, 2003). 

     

    Fat-related helpers

    Fats in food are made up primarily of triglycerides, a molecule consisting of a glycerol backbone and three fatty acids. During digestion, enzyme lipase breaks down this molecule into a monoglyceride (glycerol + 1 fatty acid) and two free fatty acids. These ‘released’ molecules combined with bile acids – called micells – form the prerequisite for absorption.

    Natural milk fat contains beta-palmitate with a special structure. Whereas triglycerides in vegetable oils have what is called the POP structure (palmitic acid mainly at the external or alpha-positions), palmitic acid in milk triglycerides is predominantly located in the centre or beta-position. Released palmitic acids from POP, together with calcium, form non-absorbable fat soaps. Clinical trials show that beta-palmitate, in contrast, can be efficiently absorbed, avoiding the formation of fatty-acid soap.  Accordingly, its beneficial effects include increased calcium absorption, softening of the stool (Havlicekova et al, 2016), as well as less crying time (Litmanovitz et al, 2014) and less colic (Nocerino et al, 2015).

    In addition, medium-chain triglycerides (MCT), as naturally found in some vegetable oils like coconut oil, are more easily digested because MCTs bypass the steps necessary for the absorption of long-chain fats. Consequently, they provide a source of calories while reducing the amount of malabsorbed fat remaining in stools (Gracey et al, 1970). They help to maintain adequate nutrition, which is especially important in the case of diarrhoea (Tanchoco et al, 2007). 

     

    Protein-related helpers 

    Proteins are composed of one or more chains of their basic units (called amino acids). During digestion, proteins are enzymatically degraded (hydrolysed) to peptides (shorter chains of amino acids) and finally to absorbable free amino acids. As a protein-related natural solution for digestive problems or (a risk of) allergies, ‘pre-digested’ (cow’s milk) protein can be used to different degrees:

    Slightly hydrolysed protein
    Several randomised controlled trials demonstrate the usefulness of hydrolysed formulas in the management of infantile colic (Vandenplas et al; 2013b, Iacovou et al, 2012).

    Partially hydrolysed protein
    The German Society for Allergology and Clinical Immunology (DGAKI) and the German Society for Pediatric and Adolescent Medicine (DGKJ) state in their guidelines for allergy prevention: Children who are not breastfed, or are only partly breastfed due to being at risk of allergy, should receive hydrolysed infant formula (Koletzko et al, 2013). A randomised, controlled study – of 103 full-term infants aged 6-8 weeks who bore a risk of allergy – shows hydrolysed formula reduces symptoms of atopic dermatitis in the medium-term (i.e. until the sixth month of age – the end of the study's observation period) (Boženský et al, 2015).

    Extensively hydrolysed protein 
    Extensively hydrolysed protein-based formula (EHF) is considered the first line of management in cases of cow’s milk protein allergy (CMPA) (Vandenplas et al, 2014).

    Free amino acids 
    Extremely sensitive infants with multiple severe allergies might react to residual allergens in EHF, and therefore require special care. In order to completely avoid an allergic reaction, the feeding of free amino acids based formulas (AAF) is required (Vandenplas et al, 2007). 
    In conclusion, the higher the degree of degradation (hydrolysis), the easier the formula is to digest and the lower is the allergenicity. 
    An allergic reaction is caused by a certain sequence of amino acids (antigen/epitope) specific to the source of protein, e.g. cow’s milk. Consequently, the usage of vegetable-protein based formulas like protein from soy or rice is an alternative approach to CMPA management (Katz et al, 2014).

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