The interplay between malnutrition, persistent diarrhea, lactose intolerance, and food associated gut dysbiosis in children; a comprehensive review

Abstract

Background

Persistent diarrhea, lactose intolerance, and gut dysbiosis are major gastrointestinal conditions that worsen malnutrition in children, especially in low and middle-income countries. Due to these factors, there is a vicious cycle in which diarrhea worsens malnutrition by reducing the gut’s capacity to absorb nutrients. Persistent diarrhea is defined by WHO, diarrhea (≥ 3 loose/watery stools daily) lasting 14 days or longer posing higher risk of malnutrition than acute diarrhea.

Methods

This review explores the interconnected nature of these conditions and their cumulative impact on child health and development. A comprehensive literature review was conducted using databases such as Google Scholar, PubMed, Web of Science and Scopus, focusing on studies examining the pathophysiology, clinical manifestations, and management strategies in malnourished children. This review explores current evidences on etiology (E. coli, Cryptosporidium, sequential infections), pathophysiology (malabsorption, villus atrophy, enteric inflammation), dietary interventions (zinc, vitamin A, glucose-polymer ORS) and microbiome-based (probiotics, dysbiosis, correction) strategies of persistent diarrhea.

Results

Findings show that persistent diarrhea causes mucosal damage and nutrient malabsorption, while secondary lactose intolerance leads to osmotic diarrhea and further caloric loss. Gut dysbiosis, marked by the depletion of beneficial bacteria and overgrowth of pathogens, impairs digestion, disrupts immune function, and sustains chronic inflammation. Together, these conditions create a vicious cycle that perpetuates malnutrition and stunting. Recommended interventions include oral rehydration therapy, lactose-restricted diets, micronutrient supplementation (particularly zinc and vitamin A), and microbiota-based therapies such as probiotics and prebiotics.

Conclusion

The review concludes that integrated approaches—combining nutritional support, microbiome restoration, and improved hygiene—are essential for breaking the cycle of malnutrition and gastrointestinal disease. Addressing these issues through targeted public health policies and personalized interventions can significantly improve outcomes for vulnerable pediatric populations.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12887-026-06529-8.

Introduction

Persistent diarrhea is a major threat to public health in low and middle income countries (LMICs), and the second leading cause of childhood mortality worldwide [1]. Persistent diarrhea is defined, in line with WHO criteria, as diarrhea lasting 14 days, which is clinically distinguished by its chronic nature, increased risk of dehydration and increased risk of malnutrition and metabolic derangement. Children with malnutrition are more likely to have a long duration of diarrhea due to poor immunity, damaged gut lining, and poor rates of recovery [2, 3]. In a South Asian and sub-Saharan Africa study of undernourished children with persistent diarrhea, childhood mortalities were significantly higher than children who were well-nourished, therefore establishing a reciprocal relationship between malnutrition and diarrhea [4, 5]. Diarrhea is a common coexisting condition in children, and the condition of lactose intolerance that often ensues exacerbates the problems related to malnutrition. It is caused by lack of lactase enzyme, which breakdown lactose into glucose and galactose, usually as a result of damage to the lining of the jejunum following recurrent infections [6, 7]. Lactose malabsorption leads to osmotic diarrhea, abdominal discomfort and other intestinal loss nutrients hindering growth characters and cause malnutrition in children [8, 9].

Gut dysbiosis, a disruption in the composition of intestinal microbiota, has been identified as one of the significant factors in persistent diarrhea in malnourished children [10, 11]. Prolonged episodes of enteric infections, frequent use of antibiotics, and low food intake contribute to an imbalance in the gut microbiota, leading to the proliferation of pathogenic bacteria and the depletion or loss of beneficial bacteria, such as Lactobacillus and Bifidobacterium [12, 13]. Besides, gut dysbiosis leads to chronic inflammation and malabsorption of nutrients, thus exacerbating the nutritional status of such children [11, 14]. Given the significant patient-to-patient variability in presentations of chronic diarrhea, lactose intolerance, and gut dysbiosis, it is critical to have a systemic approach to the conditions. This review will focus on reviewing current knowledge on why malnourished children have prolonged diarrhea, the contribution of lactose intolerance that worsens the gastrointestinal health of the child, and how gut imbalances affect disease progression. Additionally, we also present an overview of evidence-based clinical management approaches, such as nutrition, probiotics agents, microbiome interventions, in pediatric population. Recognizing these underlying mechanisms allows for more targeted and effective nutritional and therapeutic approaches in settings where malnutrition and diarrhea frequently coexist.

Materials and methodology

In this review, the interconnected gastrointestinal complications of gut dysbiosis, secondary lactose intolerance, and persistent diarrhea in malnourished children were examined, with an emphasis on LMICs. The search on MeSH terms (Diarrhea/epidemiology, Malnutrition, Lactose Intolerance, Dysbiosis, Child) with free-text words (persistent diarrhea, gut microbiota, food intolerance, low- and middle-income countries) was conducted on Google Scholar, PubMed/MEDLINE, Embase, Scopus, Cochrane Library, and Web of Science. Restriction based on the lack of resources to English was used in English language, and where possible translation of gray literature was done according to PRISMA-ScR requirements. The epidemiological studies, peer-reviewed articles and reports from international organizations (FAO, UNICEF, WHO) published between 2010 and 2024 were included in this review. Both clinical and population-based studies were considered to integrate multidisciplinary perspectives from clinical nutrition, epidemiology, and public health. The purpose of the inclusion criteria was to choose research that specifically addressed malnutrition in relation to diarrhea, lactose intolerance, or disruption of the gut microbiota in children ages 0–6. Clinical trials, cohort studies, case-control studies, and narrative or systematic reviews were among the studies that qualified. Moreover, the inclusion and exclusion criteria of current study are mentioned in the PRISMA flow diagram in Fig. 1. To ensure relevance to areas where childhood malnutrition is most prevalent, studies conducted in LMICs were given priority. Articles with adult populations, animal-only or in vitro studies, non-peer-reviewed content, articles without full-text access, and studies unrelated to nutritional or clinical outcomes in pediatric patients were all excluded based on the exclusion criteria.

Fig. 1.

PRISMA flow diagram of the literature search process

The identification of 625 records—580 from database searches and 45 from other sources—marked the start of the selection process. Titles and abstracts totaling 610 were screened after 15 duplicate entries were eliminated, and 420 of these were deemed irrelevant. Following a thorough review of the remaining 190 full-text articles, 93 studies were excluded. Of them, 25 were animal/lab-based studies, 48 did not concentrate on pediatric populations, and 20 were either not peer-reviewed or had full texts that were not available. A total of 120 articles remained that satisfied all requirements to be considered for the review. Two independent reviewers extracted the data, capturing important details like the study design, population demographics, the nature and duration of gastrointestinal symptoms, the presence of lactose intolerance, the composition of the microbiota, and the nutritional interventions that were used. A third reviewer was consulted in order to settle any disputes between the reviewers. These studies’ results were narratively synthesized and grouped into five thematic domains: public health, nutrition/microbiology, pathophysiology, clinical outcomes, and policy. A meta-analysis was not practical due to the heterogeneity in study methods, populations, and interventions. Rather, the review offers a qualitative synthesis that identifies important trends, connections, and gaps in the evidence regarding how gastrointestinal dysfunction affects malnutrition and child development.

Persistent diarrhea and malnutrition

Diarrheal diseases remain a leading cause of child death globally especially in LMICs where malnutrition is rife among children. Diarrhea refers to the passage of loose or watery stools for more than 14 consecutive days, which results to severe dehydration, deficiency in nutrients, and lowered immunity to diseases. Diarrhea and malnutrition are mutually reinforcing with malnutrition leading to development of diarrhea diseases, and recurrent episodes of diarrhea leading to worsening of the malnutrition status. Malnourished children are especially vulnerable to long term diarrhea due to poor immunity, altered mucosal permeability and barrier function and impaired recuperative capacity. The pathophysiological processes that underlie the development of persistent diarrhea and malnutrition in children are complex, and include mucosal lesions, increased permeability, impaired absorption of nutrients, and immuno-compromised status. The detailed pathophysiological interactions among malnutrition, persistent diarrhea, lactose intolerance and gut dysbiosis are mentioned in Table 1. In South Asian and sub-Saharan African LMICs, persistent diarrhea is strongly associated with inadequate water, sanitation and hygiene (WASH) infrastructure, household food insecurity, and delayed healthcare access, which together amplify its impact on child growth and survival.

Table 1.

Pathophysiological interactions among malnutrition, persistent diarrhea, lactose intolerance and gut dysbiosis

Condition	Mechanism	Effect on child health	Interconnection with other conditions	Reference
Malnutrition	Nutrient depletion, reduces gut barriers, micronutrient malabsorption, reduces enzymes production, delayed GI maturation, impaired growth hormones axis	Weakens immunity, impaired growth and development, promotes cognitive delay	Increased permeability of intestines (leaky gut), alters gut microbiota composition, reduce production of gut enzymes that promotes lactase deficiency, contribute of osmotic diarrhea and nutrient loss	[57] [58] [59]
Persistent diarrhea	Fluid and electrolyte loss, damaged enterocytes, shortens villi, intestinal inflammation and malabsorption, mucosal damage, promotes micronutrient loss	Impacted in stunting and wasting, worsens malnutrition, long-term cognitive impairment, immune system exhaustion, developmental delay, increased risk of morbidity and mortality, causes severe dehydration, risk factor for metabolic acidosis	Increased permeability of intestines, allow pathogens and toxins to enter the blood stream, lactase deficiency (secondary lactose intolerance), growth faltering and nutrient deficiencies, promotes wasting, damaged intestinal microflora, increased risk of recurrent infection	[60] [61] [62]
Lactose intolerance	Lactase enzyme deficiency, colon bacteria ferment lactose into gases and short chain fatty acids, mucosal irritation, reduced nutrient absorption, accelerates intestinal transit and inflammation, promotes overgrowth of gas producing bacteria	Undigested lactose causes osmotic diarrhea, causes bloating, cramps, flatulence, abdominal pain, acidic stool, nutrient depletion, fluid and electrolytes imbalance, consumption of lactose containing bacteria causes repeated symptoms	Promotes and worsens diarrheal episodes, promotes persistent diarrhea due to irritation in colonic mucosa by acidic pH, secondary deficiencies and poor growth lead to severe malnutrition, exacerbates gut dysbiosis, food aversions, reduced intake leads to caloric and protein deficit	[45] [63] [64] [65]
Gut dysbiosis	Reduced diversity and imbalance between beneficial and pathogenic bacteria, impaired gut barrier and inflammation, increased risk of persistent diarrhea, delayed gut maturation, alters nutrient metabolism and produce toxic metabolites	Stresses gut-brain axis, reduced short chain fatty acids production, affects neurotransmitter, production and vagal signaling, impacts cognitive function and behavior, reduce bio-availability of vitamins and minerals	Disrupts gut homeostasis and immune modulation, disturbs colonocytes health and pH regulation, neuro developmental delay, retarded growth, contributes to prolonged and recurrent diarrhea episodes, vulnerability to pathogens and food intolerance	[66] [67] [68]

Mechanisms of persistent diarrhea in malnourished children

Persistent diarrhea in malnourished children involves impaired immunity, altered microbiota, and mucosal damage. Pathogens like E. coli, Cryptosporidium, and Giardia cause villous atrophy, epithelial destruction, and increased permeability, reducing nutrient absorption and fluid balance, leading to severe intestinal dysfunction [15]. Moreover, Pro-inflammatory cytokines like TNF-α, IL-1β, and IFN-γ increase gut permeability, disrupting tight junctions and worsening diarrhea through immune activation [16]. Diarrhea impairs nutrient absorption and utilization due to mucosal damage, reducing digestion of carbohydrates, proteins, and fats. Persistent diarrhea causes malnutrition, with decreased brush border enzymes (lactase, sucrase, maltase) and common fat malabsorption, leading to steatorrhea in affected children [17]. Malnutrition and chronic diarrhea reinforce each other; zinc deficiency worsens diarrhea by impairing epithelial function, immunity, and intestinal cell repair [18]. Vitamin A deficiency weakens immunity and reduces mucin levels, compromising gut protection and increasing susceptibility to severe gastrointestinal infections [19, 20]. Taken together, infection-based mucosal damage, micronutrient deficiencies and dysregulated immune responses lead to the cycle of persistent diarrhea and malnutrition in vulnerable pediatric populations.

Consequences of persistent diarrhea in malnourished children

Prolonged diarrhea in malnourished children causes dehydration, electrolyte imbalance, and metabolic acidosis, leading to hypovolemia and potential organ failure [21]. Persistent diarrhea in malnourished children increases morbidity and mortality. Prolonged nutrient deficiency during early development causes stunting (height-for-age z-score < -2 SD), leading to cognitive deficit, poor academic performance, and lower future income potential [22]. The complications and interventions of persistent diarrhea among malnourished children are mentioned in Fig. 2. Additionally, Malnutrition impairs immune defense by reducing T lymphocytes, B lymphocytes, and natural killer cells and lowering secretory immunoglobulin A, weakening protection against enteric pathogens [23]. These findings highlight the urgent need to improve nutrition and reduce high morbidity and mortality in children with persistent diarrhea, who face increased risks of infections and fatality rates exceeding 20% in resource-limited settings lacking adequate medical and nutritional support [24]. Comprehensive approaches toward these mechanisms include nutritional rebalancing, micronutrient replenishment, gut microbiota re-conversion, and infection prevention and control [25].

Fig. 2.

Complications and interventions of persistent diarrhea among malnourished children

Lactose intolerance in malnourished children

Lactose intolerance, common in malnourished children, results from persistent diarrhea and intestinal damage, causing poor lactose digestion and nutrient loss. Symptoms include bloating, pain, gas, and osmotic diarrhea, worsening malnutrition. Damaged lactase-producing cells and gut inflammation perpetuate malabsorption. Understanding this link supports effective nutritional interventions.

Pathophysiology of lactose intolerance

Primary and secondary lactose intolerance are the two common types of lactose intolerance that have different pathophysiological mechanisms. Genetic primary lactose intolerance stems from the human organism’s progressive decrease in lactase production with age. This condition affects more those with Asian, African, Indigenous American origins because most of them are lactose intolerant after infancy [6]. However, secondary lactose intolerance is much more important in the context of malnourished children because it occurs as a result of changes in the intestinal mucosa.

Lactose digestion takes place predominantly in the brush border of the small intestine after the action of lactase-phlorizin hydrolase also known as lactase which splits milk sugar into glucose and galactose that can be absorbed [26]. The lack of lactase leads to an inability to hydrolyze lactose, which hence remains in the intestinal lumen and is acted upon by bacteria [27]. In children suffering from chronic malnutrition, secondary lactose intolerance may be attributed to environmental enteric dysfunction (EED); a subclinical inflammation of the gut which is associated with persistent inflammation and increased permeability of the small intestine, and villous atrophy [28]. EED from repeated infections damages intestinal tissue, reduces lactase production, and increases lactose intolerance risk, hindering nutritional recovery in affected children [29].

Mechanisms of lactose intolerance in malnourished children

Malnutrition contributes to lactose intolerance through mucosal damage, inflammation, and gut microflora imbalance. Frequent infections like Rotavirus, and Shigella further harm intestinal epithelium, worsening lactase deficiency and nutrient absorption [30]. One of the major histological changes compromising the absorptive surface in this type of mucosal injury is villous atrophy – the process in which the villi become blunted and shortened [31]. This systematic review noticed the role of chronic gut inflammation in the production of lactose intolerance in malnourished children is of great significance. Inflammations thus cause the production of pro-inflammatory cytokines, including TNF-α, IL-β, and IFN-γ that distort normal intestinal permeability and affect enzyme synthesis [32]. Research shows that inflammation hinders the absorption of lactase and leads to destruction of enterocytes due to oxidative stress [33]. This chronic inflammation is further compounded by malnutrition since micronutrients such as zinc, vitamin A, and iron are crucial in stabilizing gut barrier and regulating the immune response [32].

Another factor that directly affects the emergence of lactose intolerance in malnourished children is an imbalance in the composition of gut microbiota [34]. Lactobacilli and Bifidobacterium are synthesize bacterial lactases, which enhance lactose digestion; however, malnourished children with persistent diarrhea exhibit markedly low levels of beneficial bacteria [35]. This depletion goes on and hampers lactose degradation contributing to the fermentation of undigested lactose by pathogenic bacteria such as E. coli and C. difficile which lead to worsening of the inflammation of the gut microbiome and diarrhea [36]. Furthermore, malnourished children harbor more pathogenic bacteria producing toxins that increase gut permeability and cause lasting effects on lactose tolerance. Recent studies show probiotics and prebiotics help restore gut balance and improve lactose intolerance in undernourished children [2, 37]. Effective measures include lactose-free or low-lactose diets, zinc and vitamin A supplements and the use of probiotics have been used in treating the malnutrition and lactose intolerance problems with success in children [38].

Clinical manifestations of lactose intolerance in malnourished children

In malnourished children, lactose intolerance worsens nutritional and gastrointestinal issues. Undigested lactose causes bloating, cramps, and osmotic diarrhea, reducing nutrient absorption. Fermentation by gas-producing bacteria increases intestinal distension, while reduced Lactobacillus and Bifidobacterium, worsen microbial imbalance and digestive discomfort [39]. Abdominal pain brought on by the hyperosmolar effects of undigested lactose drawing water into the intestinal lumen and causing excessive peristaltic movement is another typical symptom. In addition to changing cytokine profiles, EED caused by chronic malnutrition increases gut permeability and inflammatory responses, exacerbating gastrointestinal distress [40].

Osmotic diarrhea, which causes severe fluid loss and dehydration, is one of the most serious side effects. The buildup of unabsorbed lactose produces an osmotic gradient that keeps water in the colon, causing loose, acidic stools that frequently irritate the perianal area [41, 42]. Acute dehydration, a potentially fatal consequence in already susceptible malnourished populations, is exacerbated by this ongoing fluid loss in addition to electrolyte imbalances. Furthermore, lactose intolerance limits dairy intake, reducing protein and calcium absorption, while chronic diarrhea further impairs growth, immunity, and tissue repair. Removing dairy from malnourished children’s diets exacerbates pre-existing nutrient deficiencies and hinders recovery [43]. Previous studies also evidenced that children with persistent diarrhea and lactose intolerance had significantly lower weight-for-age Z-scores. Due to inadequate intake and absorption, these kids find it difficult to catch up on growth, making them susceptible to immunological compromise and developmental delays [44]. In many low-resource pediatric settings, a carefully monitored trial of a lactose-free diet is therapeutically used to confirm diagnosis and guide treatment.

Diagnosis of lactose intolerance

Diagnosis of lactose intolerance in malnourished children requires a multifaceted approach involving clinical evaluation, dietary history, and confirmatory laboratory tests to identify lactase deficiency. For the diagnosis of lactose malabsorption, the hydrogen breath test is generally regarded as the gold standard. This noninvasive test involves consuming a lactose-containing solution and measuring the amount of hydrogen in the breath; a high hydrogen level suggests that lactose digestion is not complete because of a lactase deficiency [45]. The lactose tolerance test, which measures blood glucose levels after consuming a lactose solution, is an additional diagnostic technique. When lactose is broken down into glucose and galactose in people with normal lactase activity, blood glucose levels raise noticeably. However, there is little to no increase in glucose in lactose-intolerant people, which may indicate poor digestion [46]. Hydrogen breath tests may cause discomfort in undernourished children, while lactose elimination diets offer a simpler, safer diagnostic approach [47].

Gut dysbiosis, persistent diarrhea and malnutrition

The gastrointestinal tract is lined by a highly microbiota which is involved in processes such as digestion, metabolism, and immune regulation, has a significant impact on health. Gut microbiota is a group of microorganisms that live in the intestines involved in digestion of complex carbohydrates, synthesis of vitamins and short-chain fatty acids, and controlling immune responses. Dysbiosis, chronic diarrhea, reduced gut motility, increased intestinal permeability, and the subsequent inflammation led to repeat infections which further augment the deterioration in malnutrition and growth failure. The consequences of gut dysbiosis in malnourished children are mentioned in Fig. 3. A healthy gut microbiota is characterized by high diversification of bacterial flora in which Lactobacillus, Bifidobacterium, and F. prausnitzii predominate, which have specific functions in the health of the intestinal tract [48]. These bacteria are involved in the fermentation of dietary fibers, and they produce products like butyrate that act as energy source to the epithelial cells lining the intestines and enhance barrier function [49]. Gut dysbiosis on the other hand is characterized by reduced microbial complexity, high levels of pathogenic organisms and reduced levels of symbionts. In malnourished children, dysbiosis is typically associated with the higher number of facultative anaerobes including E.coli, Salmonella and C. difficile that are inflammatory obligates which cause diarrhea and damage to the intestines for a further longer period [2]. Gut dysbiosis and EED represent interlinked consequences of chronic intestinal insult rather than isolated pathological entities; both reflect sustained exposure to enteric pathogens, inadequate diet and poor hygiene and sanitation, and both contribute to impaired nutrient absorption and linear growth faltering.

Fig. 3.

Consequences of gut dysbiosis in malnourished children

Causes of gut dysbiosis in malnourished children

Gut dysbiosis in malnourished children results from a complex interaction between inadequate environmental hygiene, frequent infections, poor dietary intake, and excessive antibiotic use. A major factor in upsetting the delicate microbial balance in the gut is nutritional deficiencies. Nutrients like dietary fibers, proteins, and micronutrients that support the growth of good bacteria—especially those that produce short-chain fatty acids—are essential for a healthy gut microbiota [50]. Limited consumption of these nutrients in malnourished children leads to the loss of beneficial microbial species such as Lactobacillus and Bifidobacterium, are both essential for fermenting carbohydrates and preserving intestinal integrity [51]. The production of vital bacterial-derived vitamins, like vitamin K and B-complex vitamins, is hampered by the lack of microbial diversity, further undermining the functions of intestinal mucosa. Since pathogenic infections displace beneficial microbes and cause systemic inflammation, they harm the intestinal mucosa and worsen dysbiosis, especially when they originate from E. coli, Salmonella, C. difficile, and Rotavirus [52]. Children who experience recurrent diarrhea their gut microbiota remains poor and more inflammatory in taxa [53]. Environmental enteric dysfunction (EED), a subclinical condition characterized by chronic inflammation and nutrient malabsorption that feeds the cycle of malnutrition and microbial imbalance, is also closely associated with persistent enteric infections [15].

Excessive antibiotic use in undernourished children is another driver of dysbiosis. While necessary for treating bacterial infections, antibiotics indiscriminately eliminate pathogens, creating an ecological void that favors resistant organisms like C. difficile [14]. Early-life antibiotic exposure can cause long-term changes in gut flora, increasing the risk of immunologic and metabolic dysfunctions later in life [54]. Consequently, antibiotic stewardship and parallel microbiota-supportive strategies (probiotics, prebiotics, and improved diet) are essential to restore gut health in this population. Environmental and hygiene-related factors contribute strongly to dysbiosis. Children are exposed to enteric pathogens through unsafe water, inadequate sanitation, and poor hygiene, which worsen malnutrition and gut imbalance [55]. Environmental pollutants such as heavy metals and pesticides further disrupt microbial composition and promote inflammation [56]. To break the cycle of malnutrition and dysbiosis in vulnerable pediatric populations, nutritional rehabilitation must be combined with robust WASH and environmental health interventions.

Consequences of gut dysbiosis in malnourished children

Malnutrition in children affects in many ways due to gut dysbiosis, main effects include poor nutrition absorption, inflammation, and messed up gut movement. The gut microbiota contributes to the digestion and absorption of nutrients, the modulation of the immune system, and the regulation of the intestinal homeostasis. This review paper also confirms the need for a more comprehensive public health approach to recognize and address the complex impacts that pathogenic gut dysbiosis have for the health of malnourished children and for the development of effective methods for microbial re-balancing.

Impaired nutrient absorption

Another major impact of gut dysbiosis in malnourished children is that the gut is unable to absorb crucial nutrients this only serve to worsen the malnutrition and contribute to developmental issues in the Children. Thus, the gut microbiota contributes to the degradation of polysaccharides, fermentation of dietary fiber and short-chain fatty acids (SCFAs) including butyrate, acetate and propionate. These SCFAs are important to the health of large intestine as they act as source of energy for colonocytes, strengthen the mucosal barrier, and regulate inflammation [69]. However, in the study conducted amongst children undergoing malnutrition, dysbiosis is marked by a decrease in SCFA producing organisms, thus reducing SCFA levels and nutrient utilization capacity [70].

Previous research evaluating the gut microbial profile documented that evaluated the gut microbial profile of children with severe acute malnutrition and the results showed that they had low levels of Faecalibacterium prausnitzii and Roseburia are known to produce butyrate [71]. This retardation weakened the epithelial lining of the guts hence, increased permeability and nutrient loss. Also, SCFAs have an impact on the release of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), gut movement and satiety hormones [72]. A decrease in SCFAs alters these regulatory mechanisms, limiting nutrient substrate utilization and prolonging energy knockdown effects in malnourished children. However, reduction of SCFA and other essential nutrients, dysbiosis influences the availability of vitamins and minerals in the gastrointestinal tract. Supplementation of the gut microbiota synthesizes several water-soluble vitamins like Vitamin B₁₂, folic acid, and biotin, these are important for cellular metabolism as well as neuronal development [73]. The gut microbiota also plays a crucial role in the absorption of zinc since a constant balance of microbial population is required for preservation of the transporters on the mucosa of the intestine [74]. Since zinc deficiency has been described as influencing worsened diarrhea severity and immune function, gut dysbiosis is a major factor that predisposes patients to the occurrence of malnutrition-related complications.

Increased gut inflammation

Periodontal disease and gut dysbiosis in stunted children are directly associated with chronic inflammation that prolongs and worsens diarrheal cases and hinders the repair of the mucosa. A healthy gut flora provides a healthy immune response and keeps inflammation in check to avoid tipping towards pro-inflammatory bacteria species. However, in dysbiosis, this balance is broken and the immune reaction continues and the bowel inflammation lasts. Dysbiosis in terms of inflammation is precipitated by gram-negative bacteria including E. coli, Klebsiella pneumoniae and Salmonella species which have lipopolysaccharides (LPS) that are components of the outer membrane. LPS serves as a strong inducer of pro-inflammatory cytokines such as the TNF-α, IL-1β and IL-6 through TLR4 pathways [75]. LPS impairs intestinal healing and perpetuates diarrhea in malnourished children; this results in systemic inflammation referred to as metabolic endotoxemia. Additionally, impact on regulated substances such as Bifidobacterium and Lactobacillus causes loss of signals that advance anti-inflammation. Some of these bacteria release metabolites such as indole-3-propionic acid and tryptophan derivatives that bind to the aryl hydrocarbon receptors that in turn increases the release of the anti-inflammatory cytokine IL-10 [76]. The absence of these protective mechanisms in dysbiotic gut environments increases inflammation and the risk for further destruction of the gut lining and increased permeability in malnourished children. Previous studies have shown the relationship between gut dysbiosis and inflammation to EED, a condition that has been observed in children who suffer from malnutrition and live in unhygienic conditions [77]. Thus, chronic, low-grade intestinal inflammation leading by dysbiosis and EED is a central pathway linking poor environments to growth faltering and impaired cognition and neurodevelopment.

Altered gut motility and function

Imbalances in gut flora significantly affect intestinal motility and the functionality of the intestine, which contribute to the development of chronic gastrointestinal diseases in malnourished children. Firstly, gut microbiota regulates peristalsis, which refers to the contractions of the intestinal muscles that enable the movement of food and waste products in the gut. Dysbiosis impairs this regulation thereby causing increased gut motility leading to continuous diarrhea or reduced motility that makes children more prone to constipation and bacterial overgrowth. Several processes play a role in the slowed gut motility characteristic in malnourished children with dysbiosis. One of the key reasons is related to the disruption of the enteric nervous system (ENS), which is responsible for gut motility and interacts with the microbes within the gut through metabolites [78]. For instance, useful bacteria synthesize neurotransmitters including serotonin (5-hydroxytryptamine) and gamma-amino butyric acid (GABA), which control intestinal smooth muscle contractions that facilitate bowel motions [79]. In dysbiosis these signals are missing and results to morbid alterations in motility, resulting in either increased motility or decreased motility or constipation. In the same respect, dysbiosis does alter the metabolism of bile acids and plays a role in the gut motility. The gut microbiota is an important factor involved in the deconjugation of bile acids, which act as regulators of water and electrolyte in the intestines [72]. Imbalances in the complexity create increased levels of BA in the colon, which together with other BA abnormalities result in secretory diarrhea and worsened malabsorptive symptoms in malnourished children.

Interventions and management of persistent diarrhea, lactose intolerance in malnourished children

Management of persistent diarrhea in malnourished children should follow a step wised clinical approach that includes: (1) stabilization and rehydration and management of metabolic complications; (2) nutritional rehabilitation; (3) etiological treatment of infections and lactose intolerance; and (4) long-term prevention strategies that address WASH, dietary management and recurrent infections. Gut dysbiosis and lactose intolerance in malnourished children should therefore be managed by a combination of nutritional support, microbiota repletion, and approaches to obtain adequate hydration to alleviate intestinal dysfunction and enhance other aspects of health. Oral rehydration therapy is the main area of intervention aiming to prevent dehydration; diet is the second one that is targeted at reducing symptoms and improving nutrient uptake; the third type of intervention is microbiota-targeted therapies, excluding the use of antibiotics with bacteria, including probiotics and prebiotics. These strategies focus on interventions to stop the cycle of malnutrition and diarrhea and to help children regain their health and cut down on their rate of sickness. The therapeutic approaches targeting the cycle of malnutrition, lactose intolerance, persistent diarrhea, and GI complications in children are discussed in Table 2.

Table 2.

Therapeutic approaches targeting the cycle of malnutrition, lactose intolerance, persistent diarrhea and GI complications in children

Intervention	Target condition	Mechanism	Evidence study
Breastfeeding promotion (0–6 months)	Infants’ malnutrition	Provides ideal nutrition and antibodies, Prevent early exposure to contaminated foods	[113]
Ready to use therapeutic foods (RUTF, F-75, F-100)	Severe acute malnutrition	Provide high calorie, micro-nutrient dense, nutrition to support catch-up growth and recovery	[114]
Oral rehabilitation therapy	Persistent diarrhea	Restores fluid and electrolytes loss, Prevents dehydration	[81]
Zinc and vitamin A supplementation	Persistent diarrhea, Malnutrition, Micronutrient deficiencies	Promotes mucosal repair, Prevents intestinal leakage, Improves immunity	[82, 102]
Lactose free diet	Primary/secondary lactose intolerance	Prevents undigested lactose fermentation and associated GI symptoms	[115]
Lactase enzyme supplementation	Lactose intolerance	Breakdown lactose into glucose and galactose before reaching the colon	[116]
Probiotics (Lactobacillus and Bifidobacterium)	Disrupted gut microbiota	Replenish beneficial bacteria, Restore gut microbial balance, Enhance gut barrier and immune modulation	[92]
Prebiotics (Inulin, fructooligosaccharides, and galactooligosaccharides)	Low beneficial bacterial diversity	Provides fermentable fibers that feeds beneficial bacteria and promote their growth	[93]
Synbiotic (Probiotics + Prebiotics)	Severe dysbiosis	Synergistic effect of microbial restoration and feeding of probiotics	[96]
High fiber diet (fruits, vegetables, whole grains)	Low microbial diversity and poor gut health	Promotes growth and commensal microbes and SCFA production (butyrate, acetate) for gut integrity	[117]
Food fortification	Malnutrition and nutrients deficiencies	Enhances commonly consumed foods with essential nutrients to prevents deficiency	[103]
Nutritional education and dietary diversification	Chronic and hidden hunger	Improves knowledge and practice of balance diet intake, promotes inclusion of locally available nutrient rich foods	[118]
Fecal microbiota transplantation	Severe dysbiosis	Transfer healthy microbiota to restore normal microbial consumption	[112]
Safe water supply and household water cleaning boiling	Waterborne infections, persistent diarrhea	Reduces ingestion of enteric pathogens	[106]
Improved sanitation facilities and safe disposal of child stool	Recurrent enteric infections	Interrupts fecal–oral transmission	[107]
Handwashing with soap at critical times	Acute and persistent diarrhea	Removes pathogens; prevents person-to-person transmission	[106]
Household and food hygiene practices	Food-borne GI infections	Prevents contamination during food preparation and feeding	[108]
Environmental hygiene and WASH behavior change	Environmental enteric dysfunction	Reduces chronic pathogen exposure and gut inflammation	[106]
Safe water supply and household water cleaning boiling	Waterborne infections, persistent diarrhea	Reduces ingestion of enteric pathogens	[107]
Improved sanitation facilities and safe disposal of child stool	Recurrent enteric infections	Interrupts fecal–oral transmission	[108]
Handwashing with soap at critical times	Acute and persistent diarrhea	Removes pathogens; prevents person-to-person transmission	[106]

Dietary modifications in persistent diarrhea

Nutrition repletion forms the cornerstone of managing persistent diarrhea, lactose intolerance, and gut dysbiosis in malnourished children. One of the most critical complications in such cases is dehydration, which can rapidly become life-threatening. According to the WHO, oral rehydration solution (ORS) is the standard and most effective method to prevent and treat dehydration resulting from diarrhea. The WHO-recommended ORS contains glucose, sodium, potassium, chloride, and bicarbonate or citrate in specific proportions to restore lost electrolytes and fluids [80]. Studies confirm that ORS significantly reduces mortality in children suffering from acute and persistent diarrheal diseases, particularly in areas where intravenous rehydration is not feasible [81]. Additionally, zinc supplementation has been shown to shorten the duration and severity of diarrhea by promoting mucosal repair and enhancing immune function [82].

In children affected by lactose intolerance, dietary modifications play a key role in minimizing gastrointestinal distress and promoting nutrient absorption. When secondary lactose intolerance occurs due to diarrhea and intestinal mucosal damage, lactose-restricted or lactose-free diets are typically recommended. Avoiding dairy products helps relieve osmotic diarrhea and prevents further malabsorption complications [83]. However, the exclusion of dairy from the diet can lead to deficiencies in calcium, vitamin D, and other essential nutrients necessary for healthy bone growth and maintenance. To prevent long-term complications such as rickets and impaired bone development, fortified alternatives like soy or almond milk, along with calcium and vitamin D supplements, are advisable [84].

Besides, the green banana resistant starch and pectin can alleviate malnutrition by enhancing nutrient absorption, counter dysbiosis through prebiotic effects in favor of Lactobacillus and Bifidobacterium, decrease osmotic load associated with secondary lactose intolerance, and also reduce persistent diarrhea caused by E. coli and rotavirus [85]. Moreover, previous studies show that therapeutic use of fermented dairy and prebiotic-rich interventions has a potential to disrupt the malnutrition-persistent diarrhea-lactose intolerance-dysbiosis cycle [83, 85]. Yogurt supplementation of infants at risk of stunting in Bangladesh was found to increase the dietary diversity and positively correlated with linear growth improvements relative to both education and care as usual, indicating the potential of yogurt in restoration of microbiota and nutrient absorption during the weaning period [86]. In the same way, probiotic and synbiotic treatment in malnourished children improved weight gain and height velocity, whereas in severely acute malnourished babies Bifidobacterium infantis supplementation increased recovery in nutritional rehabilitation through beneficial gut colonization. These results confirm collectively the food-based interventions that could be used as culturally-appropriate supplements to WHO treatments in LMIC settings to treat gut dysbiosis.

Incorporation of probiotics and prebiotics

For the treatment of gut dysbiosis and related gastrointestinal disorders in undernourished children, probiotics and prebiotics present promising therapeutic approaches. Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii are the most well-researched strains of probiotics, are live microorganisms that provide health benefits when taken in sufficient amounts [87]. By improving gut barrier function, encouraging the production of antimicrobial peptides, and preventing pathogen adhesion to the intestinal lining, LGG has been demonstrated to be especially effective in treating both acute and chronic diarrhea [88].

Another beneficial probiotic is S. boulardii, non-pathogenic yeast that is particularly helpful during antibiotic treatment because of its resistance to both antibiotics and stomach acid. It lowers the risk of Clostridium difficile infections, promotes the production of IgA, and aids in the neutralization of bacterial toxins [89–91]. By specifically promoting the growth of advantageous gut bacteria like Bifidobacterium and Lactobacilli, prebiotics—non-digestible dietary fibers like insulin and fructo-oligosaccharides (FOS)—complement probiotics [92]. In turn, these bacteria boost the production of SCFAs, especially butyrate, which improves the integrity of the gut barrier and lowers inflammation. Prebiotics consumption has been demonstrated to enhance nutrient absorption and restore gut microbiota balance in malnourished children [93]. These intervention approaches are mentioned in Fig. 4. Inulin supplementation dramatically raised Bifidobacterium levels and enhanced gut barrier function, according to a randomized study by [94]. Furthermore, prebiotics improve calcium absorption, providing nutritional support for children who are lactose intolerant and cannot eat dairy [95]. Synbiotic—a combination of probiotics and prebiotics—offer synergistic benefits by boosting immune responses and reestablishing microbial balance at the same time [96]. Incorporation of synbiotics into nutritional rehabilitation programs may therefore provide a comprehensive and sustainable strategy for tackling both dysbiosis and lactose intolerance in undernourished children.

Fig. 4.

Interventions for gut dysbiosis

Zinc supplementation in reducing diarrhea severity

Zinc is vital for intestinal integrity, immune regulation, and enzyme function in growth and development. Deficiency worsens persistent diarrhea by increasing infection risk and delaying gut healing. WHO recommends zinc supplementation to reduce diarrhea duration, severity, and under-five mortality among malnourished children [97]. There are several ways by which the benefits of zinc manifest themselves. Zinc also increases the tight junction proteins in the intestinal epithelium and minimizes excess loss of water from intestines [98]. Additionally, zinc supplementation is able to influence the immune system and the cytokine pendulum, increasing the production of anti-inflammatory cytokines and reducing excessive inflammation, which affects the mucosa [99]. Zinc also has an effect on the ability of enteropathogens including enterotoxigenic E. coli (ETEC) and Vibrio cholerae to adhere and cause virulence, both are major sources of infectious diarrhea in malnutrition children [100]. Clinical studies show zinc supplementation reduces diarrheal duration, stool volume, and severity. Trials report up to 30% lower risk and fewer hospitalizations in zinc-supplemented children [101]. These findings stress the necessity of the inclusion of the zinc in diarrhea treatments and provisions especially in children who are most likely to be zinc deficient from their diets and are likely to lose more zinc through their gastrointestinal tracts.

Vitamin A and iron supplementation for immune support

Two other minor nutrients include vitamin A and iron that are essential for immunity and growth, as well as the maintenance of the body’s epithelial layer. The consumption of vitamin A is relatively low in LMICs hence having adverse effects on the public health of such societies, since it leads to increase in childhood mortality, poor gut health and increased susceptibility to infections. Vitamin A is well known to help maintain mucosal immunity and integrity and this crucial function is related with immune regulation, which involves T cell development and maturation, chiefly in the gut associated lymphoid tissues. Some of the works have noted that vitamin A intervention to the children lowers the risk of serious diarrheal diseases and respiratory infections hence the overall child’s mortality rate decreases [102].

Iron deficiency impairs brain and immune function, worsening anemia. Excess iron, however, promotes gut inflammation and pathogen growth i.e. Salmonella and Shigella, aggravating chronic diarrhea. As indicated earlier, high levels of iron intake can stimulate inflammation in the gut and encourage the growth of pathogens like in the intestines, resulting in more harm to the gut lining [103]. In view of this, the supplementation with iron in children with inflammatory intestinal diseases resulted in increased permeability of the gut and increased dysbiosis, thereby should be monitored in malnourished children with diarrhea. As a result, iron supplementation should be used carefully and with the possible additional approaches of maintaining gut microbiota, including prebiotics and probiotics ones [57].

Antibiotic and antimicrobial therapy: benefits and risks

In confirmed cases of bacterial infection, antibiotics are vital in treatment, but their overuse and improper application are associated with poor gut health and chronic allopathic microbiome changes. The prudent use of antibiotics is crucial as this avoids complications in the management of severe infection while ensuring that the infections are controlled. Oral antibiotics are advised for cases of dysentery (bloody diarrhea) and for presumed bacterial etiology like Shigella, Salmonella and C. difficile especially in those children with United Nations Children’s Fund, 2009 considering severe acute malnutrition as a moderate to severe malnutrition. Although antibiotics help treat bacterial infections, they harbor lots of risks, which include reduced gut flora, increased resistance of pathogenic bacteria, and increased susceptibility to infections. Fluoroquinolones and cephalosporins exert a detrimental impact on the gut microbiota specifically and are most likely to cause antibiotic-associated diarrhea. The antibiotic use in children results in long-term alterations in gut microbiota, with an emphasis on the decrease of Bifidobacterium and Lactobacillus species confirmed in meta-analysis [104]. Antibiotic stewardship protocols are therefore essential to ensure appropriate indications, choice and duration of therapy in pediatric populations. Adjunctive probiotics (especially S. boulardii and LGG) and, in selected cases, fecal microbiota transplantation (FMT) can partially mitigate antibiotic-induced dysbiosis [105].

Hygiene and sanitation interventions

Hygiene and sanitation education are vital to prevent diarrhea and malnutrition. Clean water, proper sanitation, and hand washing reduce infections and improve child growth outcomes [106]. Education and promotion of access to safe water at the household level through chlorination, filtration, and solar water disinfection has discouraged the use of contaminated water and have resulted in reduced incidence of diarrhea in children by up to 50% as postulated by [107]. Another highly effective intervention is hand washing with soap, as the research shows that children who wash their hands frequently get 40% less diarrheal diseases [108]. Preventive strategies must integrate maternal health education, WASH promotion, timely early and safe initiation complementary feeding, vaccination, growth monitoring, and early infection control within primary healthcare and community programs. These measures not only prevent acute episodes but also reduce repeated insults that drive EED, dysbiosis and growth failure.

Gut Microbiome in diarrheal recovery

Gut microbiota support immunity, digestion, and gut protection. In low-resource settings, dysbiosis from infections or malnutrition causes inflammation, poor absorption, and delayed recovery in children with diarrhea [109]. Therefore, measures to restore a healthy gut microbiota and interventions such as zinc supplementation are crucial in the treatment of diarrheal diseases in children. Probiotics use on a targeted basis has gained popularity as a potentially effective strategy to replenish good bacteria and aid in gut healing. Among the most researched are Saccharomyces boulardii and Lactobacillus rhamnosus, both of which have shown promise in reducing the length of diarrhea and reestablishing intestinal barrier function [110]. Commercially available probiotics, however, might not always yield the best results because gut microbiome is unique, particularly in malnourished children with different nutritional status. According to [111] future studies should focus on creating customized probiotics treatments that use metagenomic sequencing to customize interventions according to each child’s distinct microbiota composition. Moreover, FMT, which restores gut microbial balance by transferring stool from a healthy donor, has demonstrated promise in treating C. difficile infections and may be investigated for chronic diarrhea in undernourished children [105, 112]. To assess the safety, long-term effects, and possible effects of FMT on a child’s growth, immunological response, and cognitive development, extensive clinical trials are required.

Large-scale public health initiatives to address malnutrition and gut disorders

Personalized care is valuable, but community nutrition and microbiome programs remain vital for improving child health, gut balance, and long-term nutritional outcomes. Biofortifying commonly consumed foods with probiotics like Lactobacillus reuteri and prebiotics such as galactooligosaccharides can enhance gut health, reduce dysbiosis, and support early microbial development in infants [93]. Its large-scale use in government nutrition programs could be an efficient way of addressing gut health issues among vulnerable children. Government policies must address environmental causes of gut dysbiosis and malnutrition by improving water, sanitation, and hygiene infrastructure to reduce infections and enhance long-term gut health outcomes [119]. More research is also required to understand the roles that climate change plays on food security and on the gut. Climate change has emerged as a significant risk factor influencing food access and quality which in turn influences the composition of gut microbiota by offering either new dietary options or relaying direct exposure to dietary pathogens [120]. Efforts within public health policies must be aimed at promoting climate-smart agriculture and sustainable foods to provide constant food supply to support microbiome in children in vulnerable areas.

Strengths and limitations of study

This review demonstrates methodological robustness through a comprehensive and systematic literature search conducted across multiple international databases, including PubMed, Embase, the Cochrane Library, Web of Science, Google Scholar, and Scopus. The search covered a broad time frame from 2010 to 2024. A multidisciplinary perspective was integrated, synthesizing clinical, epidemiological, nutritional, microbiological, and public-health research to capture the multi-factorial nature of gastrointestinal dysfunction in malnourished children. The literature search was restricted to English-language publications, which may have excluded relevant studies from non-English-speaking regions. As a narrative review, the study is inherently susceptible to selection bias, and the lack of quantitative synthesis limits direct comparison of intervention effectiveness. The limited availability of high-quality randomized controlled trials from LMICs limits the strength of evidence, with many included studies being observational. Heterogeneity in study designs, may limit the generalizability of conclusions. Furthermore, it highlights a pressing need of the societal health strategies prioritizing the prevention of diarrhea, early-stage screening, and intervention-specific diets to alleviate the malnutrition-diarrhea bi-directionality, and identifies the obvious shortcomings of the narrative synthesis: the lack of a tool to quantify the effectiveness, conduct meta-analyses, or compare the relative effectiveness of various interventions, reliance on observational and mechanistic studies instead of randomized controlled trials.

Future research and perspectives

Treating gut dysbiosis, chronic diarrhea and lactose intolerance in malnourished children remains a major global health challenge. Although nutritional supplementation, WASH, probiotics, and antibiotic therapy have reduced morbidity and mortality, further research is needed to develop more targeted, cost-effective interventions. Advances in microbiome science and personalized nutrition provide opportunities for better outcomes. Emerging strategies include precision probiotics, tailored synbiotic and FMT to correct microbiota deficits and enhance mucosal healing. Diet modification based on individual microbial profiles may optimize nutrient absorption and immune function. Incorporating microbiome assessment into large-scale child health programs could help shape policies on food security, sanitation and maternal-child nutrition. Future clinical trials should include LMIC populations, use standardized outcomes (growth, infection rates, cognitive outcomes), and include economic evaluations to plan scale-up and policy decisions.

Conclusion

Breaking this vicious cycle is not merely a matter of treating diarrhea, but a fundamental prerequisite for ensuring the long-term health, cognitive development, and economic potential of vulnerable children worldwide. Diarrheal diseases, lactose intolerance and gut dysbiosis interact to perpetuate malabsorption, chronic inflammation, impaired immunity, recurrent infections and stunted growth. Mitigating these challenges requires holistic strategies integrating nutritional rehabilitation, microbiome-directed therapies and WASH interventions. Probiotics, prebiotics and synbiotic can modulate the microbiota, whereas therapeutic feeds and balanced diets restore energy and micronutrient reserves. Novel microbiome-based therapies such as FMT and nutraceuticals hold promise but require rigorous evaluation. Simultaneously, sustainable improvements in sanitation, clean water access and maternal-child health services are needed to prevent repeated insults to the gut. By aligning clinical innovation with strong public health action, health systems can move toward breaking the cycle of malnutrition and diarrheal disease and improving the life-course trajectories of children in resource-limited settings.

Abbreviations

EED

Environmental Enteric Dysfunction

ENS

Enteric Nervous System

ETEC

Enterotoxigenic E. coli

FAO

Food and Agriculture Organization

FMT

Fecal microbiota transplantation

FOS

Fructo-Oligosaccharides

GABA

Gamma Amino Butyric Acid

GLP-1

Glucagon Like Peptide-1

LGG

Lactobacillus rhamnosus GG

LMICs

Low and Middle Income Countries

LPS

lipopolysaccharides

ORS

oral rehydration solution

PYY

Peptide YY

RUTF

Ready to Use Therapeutic Foods

SCFAs

Short Chain Fatty Acids

WASH

Water, Sanitation, and Hygiene

WHO

World Health Organization

Authors’ contributions

SK, Conceptualization; MTS and TK, Data curation; AA and HS, Formal analysis; AAE, Funding acquisition; SK and AA, Investigation; MTS and SK, Methodology; AA and HS, Project administration; AA and MTS, Resources; S and TK, Software; AH and S, Supervision; AN and S, Validation; TK and HS, Visualization; AH, HS and SK, Roles/Writing - original draft; AH, AA, AEE, and HS, Writing - review and editing.

Funding

No funds were availed for this work.

Data availability

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.