Prebiotic, probiotic, and postbiotic properties of fermented corn starch and their application in type 2 diabetes management

Abstract

Fermented corn starch has emerged as a promising functional food due to its triad of gut biotics, prebiotic, probiotic, and postbiotic properties, which present significant potential for the management of type 2 diabetes through gut microbiota modulation. During fermentation, microbial activity alters the starch matrix, enhancing the production of bioactive compounds such as resistant starch, isomalto-oligosaccharides, and resistant dextrin, which improve insulin sensitivity, reduce inflammation, and support glycemic control. Additionally, fermented corn starch harbors beneficial microbial strains including Lactiplantibacillus fermentum, Bifidobacterium breve, and Saccharomyces cerevisiae, which reinforce gut barrier integrity, stimulate incretin secretion, and suppress systemic inflammation. Postbiotic metabolites such as short-chain fatty acids, exopolysaccharides, and bacteriocins further contribute to glucose homeostasis through immune modulation and gut hormone regulation. Despite its promise, the clinical translation of fermented corn starch is limited by safety concerns (e.g., contamination with pathogens or mycotoxins), lack of standardized fermentation protocols, and a scarcity of targeted studies. This review synthesizes current evidence on the antidiabetic potential of fermented corn starch, advocating for its integration into precision nutrition approaches and supporting further research to address safety and standardization challenges in functional food development.

Key Words: Corn starch; Prebiotic; Probiotic; Postbiotic; Hyperglycemia; Microbiota; Type 2 diabetes

Core Tip: Prebiotic, probiotic, and postbiotic properties of fermented corn starch offer promising therapeutic applications in the management of type 2 diabetes. By investigating the bioactive compounds and their influence on gut microbiota composition, insulin sensitivity, and glucose homeostasis, this review highlights the potential of these fermented products to improve metabolic health. Fermented corn starch could serve as a functional food to complement existing diabetes management strategies, offering novel microbiome-based interventions.

INTRODUCTION

Once a rare metabolic disorder, type 2 diabetes (T2D) has surged into a full-blown global epidemic, with its prevalence skyrocketing fourfold in just 3 decades. In 2024, an estimated 589 million adults (20-79 years) were living with diabetes, 90% of whom had T2D. Moreover, approximately 1.1 billion adults globally exhibit impaired glucose tolerance or impaired fasting glycemia, placing them at an increased risk of progressing to T2D. These figures are projected to rise substantially in the next 2 decades[1].

T2D is a complex heterogeneous disease, shaped by genetic, epigenetic, environmental, and lifestyle factors, along with psychosocial influences that further impact disease onset and progression. Growing evidence also implicates gut microbiota dysbiosis as a significant contributor to the development and pathophysiology of T2D[2,3]. Despite significant advances in pharmacological treatments, long-term management of T2D remains challenging, with current therapies either falling short in achieving sustained glycemic control or being burdened by adverse effects. This highlights an urgent need for alternative and complementary strategies that target both prevention and effective disease management[4].

The escalating burden of T2D has intensified the search for novel, sustainable interventions that go beyond conventional pharmacotherapy. Growing evidence has highlighted the gut microbiota as a central regulator of metabolic health, influencing insulin sensitivity, inflammation, and glucose homeostasis through mechanisms such as short-chain fatty acid (SCFA) production[5]. This has led to increasing interest in microbiota-targeted therapies, including prebiotics, probiotics, and postbiotics, as viable strategies to restore microbial balance and improve metabolic outcomes[6].

Among emerging sources, fermented corn starch presents a unique, underexplored avenue: it harbors a rich diversity of beneficial microorganisms and bioactive compounds that exhibit prebiotic, probiotic, and postbiotic properties. These microbial metabolites not only enhance gut health but also offer antidiabetic potential by modulating glucose metabolism, improving lipid profiles, and strengthening the gut barrier[7]. As functional food ingredients, strains, and compounds derived from fermented corn starch represent a promising, accessible approach to complement existing diabetes treatments and contribute to precision nutrition in metabolic disease management.

This review aimed to critically evaluate the antidiabetic potential of microbiota-targeted interventions, specifically prebiotics, probiotics, and postbiotics, derived from fermented corn starch. By integrating evidence from human clinical trials and in vivo and in vitro models, we highlight how specific compounds, such as resistant starch, isomalto-oligosaccharides (IMO), and resistant dextrin, can enhance insulin sensitivity, reduce inflammation, and improve glycemic control through microbiota-mediated mechanisms. The review also catalogs a diverse array of probiotic strains (e.g., Lactiplantibacillus fermentum, Bifidobacterium breve, and Saccharomyces cerevisiae) isolated from fermented corn starch that modulate gut barrier integrity, stimulate incretin release, and lower systemic inflammation. Additionally, the review underscores the significance of postbiotics, including SCFAs, exopolysaccharides, and bacteriocins, which exert metabolic benefits via gut hormone regulation and immune modulation. By consolidating these findings, this review not only highlights fermented corn starch as a rich reservoir of bio-functional compounds but also advocates for its integration into personalized nutritional strategies aimed at T2D management. This work supports a paradigm shift toward low-risk, food-based metabolic interventions, laying the groundwork for future translational research and functional food development.

LITERATURE REVIEW

This review was conducted in accordance with the PRISMA 2020 guidelines to ensure methodological transparency and reproducibility (Figure 1). A comprehensive literature search was performed across PubMed, Google Scholar, Web of Science, Scopus, and ScienceDirect, covering studies published between January 2000 and April 2025. Search terms included Boolean combinations such as “fermented corn starch” AND (“gut microbiota” OR “prebiotics” OR “probiotics” OR “postbiotics”) AND (“type 2 diabetes” OR “glycaemic control” OR “insulin sensitivity”), as well as related terms like “short-chain fatty acids” and “gut barrier function”. Studies were eligible for inclusion if they were in vitro, in vivo, or clinical trials published in English, and if they investigated the biochemical, microbial, or metabolic effects of fermented corn starch or its derivatives on insulin sensitivity, glycemic control, inflammation, or gut microbiota modulation. Clinical studies were included only if they had a minimum sample size of n ≥ 10. We excluded reviews, meta-analyses, conference abstracts, and non-peer-reviewed studies, as well as articles lacking methodological rigor or relevance; studies not involving gut microbiota-T2D interactions; and those published in languages other than English. Data were manually extracted and synthesized thematically. Key variables included the type of gut-biotic (prebiotic, probiotic, or postbiotic), microbial strains, mechanisms of action, experimental model (in vitro, in vivo, or clinical), and outcomes related to metabolic health. Our findings, summarized in Tables 1, 2, and 3, present the bioactive components, microbial agents, and their proposed mechanisms in relation to T2D prevention and management.

Figure 1 PRISMA 2020 flow diagram. Illustrating the selection of studies investigating fermented corn starch and its gut-biotic applications in type 2 diabetes.

Table 1 Prebiotic potentials of fermented corn starch in the management of type 2 diabetes.

Prebiotic	Study model	Treatment	Antidiabetic mechanism	Ref.
Resistant starch	Human clinical trial	Daily supplementation with 10 g of resistant starch type 2 for 8 weeks	Improved glycemic control (reduced fasting blood glucose and HbA1c), decreased insulin resistance (lower HOMA-IR), reduced inflammatory markers (hs-CRP, TNF-α), and enhanced antioxidant status (increased TAC and antioxidant enzymes, decreased MDA), indicating improved insulin sensitivity and reduced oxidative stress	[50]
Resistant dextrin	Human clinical trial	Daily supplementation with 45 g of milk powder co-supplemented with inulin and resistant dextrin for 12 weeks	Significant reductions in fasting plasma glucose (0.96 mmol/L), 2-hour postprandial glucose (1.47 mmol/L), glycosylated serum protein (16.33 μmol/L), and insulin resistance index (0.65); increases in 2-hour postprandial insulin (7.09 μIU/mL) and β-cell function index (20.43), indicating improved glycemic control and insulin sensitivity	[51]
IMO	Human clinical trial	Single ingestion of 20 g IMO; responses compared to dextrose and other carbohydrates	Stimulated insulin and incretin hormone (GLP-1 and GIP) secretion, suggesting potential benefits for glycemic control and insulin sensitivity	[52]
Maltodextrins	In vivo	Dietary substitution with maltodextrins as the primary carbohydrate source	Maltodextrins slowly release glucose until the distal ileum, activating ileal glucose-sensing and inducing GLP-1 secretion. This enhances insulin secretion and improves glucose homeostasis; the beneficial effects are mediated through GLP-1 receptor signaling	[53]
GOS	In vitro	Optimized GOS production tested on beneficial bacteria (Bifidobacterium, Lactobacillus) and for anti-inflammatory effects in TNF-α-stimulated HT-29 cells	Promoted beneficial gut microbiota growth, reduced IL-8 levels in inflamed cells, suggesting potential for improving insulin sensitivity and reducing metabolic inflammation	[52]

HbA1c: Glycated hemoglobin A1c; HOMA-IR: Homeostatic model assessment of insulin resistance; hs-CRP: High-sensitivity C-reactive protein; TNF-α: Tumor necrosis factor-α; TAC: Total antioxidant capacity; MDA: Malondialdehyde; IMO: Isomalto-oligosaccharides; GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent insulinotropic polypeptide; GOS: Gluco-oligosaccharides; HT-29 cells: Human colorectal adenocarcinoma cell; IL-8: Interleukin-8.

Table 2 Probiotic potentials of isolated microorganisms from fermented corn starch in the management of type 2 diabetes.

Microorganism	Strain	Study model	Treatment	Antidiabetic mechanism	Ref.
Lactiplantibacillus	Lactiplantibacillus brevis	In vitro	Cell-free culture supernatant and whole-cell assay	Produced bacteriocin-like substances that suppress pathogens, tolerated acidic, and bile conditions, supported gut microbial diversity, linked to improved insulin sensitivity	[57]
	Lactiplantibacillus fermentum (MCC2759)	In vivo	Oral administration of 109 CFU/mL daily for 4-8 weeks	Improved glucose tolerance, increased plasma insulin levels, reduced inflammation, enhanced intestinal barrier integrity (ZO-1), upregulated anti-inflammatory IL-10, and improved insulin sensitivity markers (GLUT-4, GLP-1, adiponectin)	[58]
	Lactiplantibacillus plantarum	In vitro	Application of live bacterial cells to epithelial cells	Enhanced intestinal barrier by upregulating tight junction proteins (occludin, claudin-1, ZO-1), improving TEER and reducing permeability	[59]
Leuconostoc	Leuconostoc mesenteroides EH-1	In vivo	Oral administration of Leuconostoc mesenteroides EH-1 fermented product rich in butyric acid	Increased butyric acid production activated Ffar2, leading to improved insulin secretion and lower blood glucose levels	[60]
Bifidobacterium	Bifidobacterium longum WHH2270	In vivo	Oral administration of Bifidobacterium longum WHH2270	Modulated gut microbiota composition, enhanced insulin sensitivity, reduced blood glucose levels, and decreased inflammation	[61]
	Bifidobacterium bifidum	In vivo	Oral administration of a probiotic mixture containing Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium animalis for 5 weeks	Improved insulin resistance and glucose tolerance; increased adiponectin mRNA expression; decreased IL-6 and MCP-1 mRNA expression, indicating reduced inflammation and enhanced insulin sensitivity	[62]
	Bifidobacterium breve	In vivo	Oral administration of Bifidobacterium breve (50 × 109 CFU/day) for 12 weeks	Improved glycemic control (reduced HbA1c and fasting blood sugar), improved lipid profile (reduced LDL-C and triglycerides), and modulation of gut microbiota composition	[62]
Saccharomyces	Saccharomyces cerevisiae	In vitro	Chromosomal integration and expression of exendin-4 peptide	Exendin-4 acted as a GLP-1 receptor agonist, enhancing insulin secretion and improving glycemic control	[63]

ZO-1: Zonula occludens-1; IL-10: Interleukin-10; GLUT-4: Glucose transporter type 4; GLP-1: Glucagon-like peptide-1; TEER: Trans-epithelial electrical resistance; Ffar2: Free fatty acid receptor 2; IL-6: Interleukin-6; MCP-1: Monocyte chemoattractant protein-1; HbA1c: Glycated hemoglobin A1c; LDL-C: Low-density lipoprotein cholesterol.

Table 3 Postbiotic potentials of fermented corn starch in the management of type 2 diabetes.

Postbiotic	Study model	Treatment	Antidiabetic mechanism	Ref.
SCFAs	Human clinical trial	High-fiber diet promoting SCFA-producing gut bacteria	SCFAs (acetate, propionate, and butyrate) improved glucose homeostasis by enhancing insulin sensitivity, stimulating the secretion of incretin hormones (GLP-1 and PYY), reducing inflammation, and modulating energy metabolism via the gut-brain axis	[68]
Lactic acid	In vivo	Steamed multigrain bread prepared from dough fermented with lactic acid bacteria	Improved oral glucose tolerance, increased liver glycogen, reduced triglyceride and insulin levels, and enhanced blood lipid profiles; the fermentation process enhanced the bread’s nutritional value and lowered its glycemic index, contributing to better glycemic control	[69]
EPS	In vivo	Administration of EPS isolated from Lactiplantibacillus plantarum JY039, either alone or combined with Lactiplantibacillus paracasei JY062	EPS enhanced the adhesion and proliferation of Lactiplantibacillus paracasei JY062, modulated gut microbiota composition by increasing beneficial bacteria (e.g., Bifidobacterium, Faecalibaculum), improved intestinal barrier function, promoted secretion of gut hormones (GLP-1 and PYY), and reduced inflammation by balancing pro- and anti-inflammatory cytokines	[70]
Brevicin 174A	In vitro	Bacterial cultures; isolation from citrus iyo fruit-production and characterization of a two-polypeptide bacteriocin (brevicin 174A-β and 174A-γ)	Exhibited broad-spectrum antibacterial activity, including against pathogens like Listeria monocytogenes and Staphylococcus aureus; such activity contributed to gut microbiota modulation, which is associated with metabolic health benefits	[71]

SCFAs: Short-chain fatty acids; GLP-1: Glucagon-like peptide-1; PYY: Peptide YY; EPS: Exopolysaccharides.

THE GUT MICROBIOME

The human gut microbiome is a complex ecosystem comprising trillions of microorganisms, primarily bacteria, residing in the gastrointestinal (GI) tract. The composition varies along the GI tract, due to factors like pH, peristalsis, and nutrient availability. As shown in Figure 2, the stomach and upper small intestine primarily contain acid-tolerant Lactobacilli and Streptococci, while the colon hosts a more diverse anaerobic population such as Clostridium, Staphylococci, and Eubacteria. The predominant bacterial groups belong to the Cytophaga-Flavobacterium-Bacteroides and Firmicutes divisions. Obligate anaerobes like Bifidobacteria, Lactobacilli, and Bacteroides, as well as facultative anaerobes such as Enterobacteria and Streptococci, are capable of colonizing the intestine. Microbial diversity in the GI tract is also influenced by factors such as host genotype, age, diet, and environmental conditions[8-10].

Figure 2 Distribution of dominant bacterial families in the human microbiota under physiological conditions. This figure illustrates the typical composition of the human microbiota in a healthy individual. Notably, the esophagus lacks a stable pH environment due to fluctuating influences from both the oral cavity and the stomach.

The gut microbiome plays a multifaceted role in human health, including metabolic functions, nutrient absorption and synthesis, immune system modulation, and protection against pathogens. It produces essential metabolites like SCFAs and vitamins, which have energetic, anti-inflammatory, and anticarcinogenic properties. The microbiome also influences the nervous system development and maintains gut barrier integrity. It interacts with xenobiotics, potentially mediating chemical toxicity and influencing disease progression. Dysbiosis, or microbial imbalance, has been linked to various conditions, including GI disorders, metabolic diseases, cardiovascular issues, and mental health problems. The gut microbiota’s metabolic functions include fermenting indigestible food substances and producing absorbable nutrients. Understanding these diverse functions can inform disease prevention strategies and novel therapies, such as fecal microbiota transplantation, prebiotics, and probiotics[8,11,12].

MICROBIOTA-METABOLIC INTERACTIONS IN T2D

T2D is primarily characterized by chronic hyperglycemia due to insulin resistance and β-cell dysfunction, compounded by inflammation and oxidative stress, which exacerbate β-cell deterioration. It is the predominant form, constituting approximately 90% of diabetes cases worldwide[13]. Factors such as genetic predisposition, sedentary habits, and population aging significantly contribute to the onset and severity of T2D. Furthermore, compelling evidence supports a connection between an imbalanced gut microbiota and the emergence of T2D[14]. In recent years, a plethora of research has established connections between the gut microbiota and T2D, with various factors such as systemic inflammation induced by the production of lipopolysaccharides[15], alterations in gut membrane permeability, and changes in bile acid metabolism[16] significantly influencing the extent of insulin resistance in the host[17]. Evidence from studies involving germ-free mice indicates that gut bacteria play a role in glucose intolerance, as these mice exhibit differing resistance levels against high-fat diet-induced insulin resistance and adiposity[5]. Investigations examining the conventional gut microbial composition in T2D have revealed significant trends in taxonomic shifts in gut bacteria, suggesting strong associations with the condition’s pathogenesis. For instance, an elevated Firmicutes-to-Bacteroidetes ratio has been linked to conditions marked by low-grade inflammation such as obesity and T2D[18]. Moreover, dysbiosis in T2D is characterized by a reduction in butyrate-producing bacterial species, particularly Roseburia intestinalis, Bifidobacterium spp., Akkermansia spp., and Faecalibacterium prausnitzii, alongside an increase in unfavorable bacteria such as Clostridium clostridioforme, Clostridium hathewayi, Clostridium ramosum, Clostridium symbiosum, Bacteroides caccae, Escherichia coli, Eggerthella spp., Fusobacterium, and mucin-degrading bacterial genera, Ruminococcus. Studies investigating the association between Lactiplantibacillus spp. and T2D have yielded inconsistent results[19,20].

Emerging evidence highlights gut microbiota dysbiosis as a key contributor to T2D and its complications. Shifts in microbial populations such as increased Bacteroidetes, Proteobacteria, and Fusobacteria have been linked to diabetic nephropathy (DN), neuropathy, and retinopathy. Specific taxa like Bacteroidota and Verrucomicrobiae elevate DN risk, while families like Victivallaceae show protective effects[21,22]. The gut-kidney axis suggests that microbial metabolites drive DN via inflammation, intestinal barrier disruption, and renal fibrosis[23]. In neuropathy, gut microbiota from distal symmetric polyneuropathy patients exacerbate peripheral neuropathy in animal models, while fecal transplants from healthy donors alleviate them, likely by modulating inflammation through competing microbial guilds[24]. Similarly, in diabetic retinopathy, gut dysbiosis and its metabolites like SCFAs and bile acids may impair ocular health by promoting inflammation and vascular dysfunction[25].

GUT-BIOTICS: PREBIOTICS, PROBIOTICS, AND POSTBIOTICS

The triad of gut biotics, prebiotics, probiotics, and postbiotics, plays a synergistic role in modulating the gut microbiota and supporting systemic health. Prebiotics, as non-digestible dietary fibers, selectively stimulate the growth of beneficial bacteria, creating a favorable environment for probiotic colonization. Probiotics, or live microorganisms administered in adequate amounts, enhance gut microbial diversity and immune responses. Postbiotics, encompassing microbial metabolites and structural components, exert health benefits without the viability concerns of live organisms, offering antimicrobial, anti-inflammatory, and immunomodulatory effects[26-28]. Collectively, these gut biotics contribute to intestinal homeostasis, inhibit pathogenic growth, and influence host physiology through mechanisms such as SCFA production, pH modulation, and interaction with gut-organ axes. While their clinical promise is evident in managing metabolic, inflammatory, and immune-mediated conditions, further investigation is essential to optimize therapeutic applications and regulatory frameworks[29].

NUTRITIONAL FACETS OF FERMENTED CORN STARCH

Corn (Zea mays) is a vital cereal rich in essential nutrients, including carbohydrates, proteins, vitamins, and minerals, alongside bioactive compounds such as β-glucan, dextrin, oligosaccharides, and resistant starch, which positively influence GI microflora and overall health. It also contains phenolic acids, flavonoids, carotenoids, and phytosterols, which contribute to the prevention of diseases such as night blindness, cardiovascular and neural disorders, and colon cancer[30-32]. Traditionally, fermenting corn with lactic acid bacteria (LAB) enhances its nutritional and sensory quality, improving protein digestibility and increasing essential vitamins such as thiamine, folate, riboflavin, vitamin C, and vitamin E. Additionally, LAB species such as Lactiplantibacillus and Lactococcus produce group B vitamins, while yeast species significantly enhance folate content during fermentation, although certain vitamins like thiamine, riboflavin, and β-carotene may decrease[33,34].

Corn starch has been used effectively in managing glycemic control for various conditions. In glycogen storage disease types I and III, raw corn starch administration can maintain normoglycemia for extended periods, improving metabolic control and growth[35]. For patients with postprandial hypoglycemic syndrome, corn starch ingestion after glucose loading can prevent hypoglycemic symptoms and reduce counterregulatory hormone responses[36]. In adults with glycogen storage disease Ia, corn starch requirements decrease with age, necessitating dose adjustments to avoid overtreatment[37]. Furthermore, the interaction between tea polyphenols and starches can modulate postprandial glycemic responses. While tea polyphenols moderately reduce glycemic response to normal or waxy corn starch, they may augment the response to high-amylose corn starch, potentially due to interactions between polyphenols and amylose[38].

Microorganisms isolated from fermented corn starch exhibit diverse probiotic applications, contributing to gut health, metabolic regulation, and potential antidiabetic effects. Several strains, such as Lactiplantibacillus brevis and Bifidobacterium longum, utilize resistant starch and oligosaccharides to produce SCFAs, which improve gut microbiota composition and energy metabolism. Probiotic strains like Lactiplantibacillus fermentum and Bifidobacterium breve enhance immune modulation, gut barrier function, and glucose metabolism, with Bifidobacterium breve specifically linked to improved insulin sensitivity. Additionally, postbiotic metabolites, including bacteriocins, exopolysaccharides, and organic acids, contribute antioxidant, anti-inflammatory, and antimicrobial properties. Saccharomyces cerevisiae and Aspergillus niger support digestion through enzyme production and gut microbiota modulation. These microbial functions collectively suggest that fermented corn starch-derived strains have the potential to influence glucose regulation, lipid metabolism, and overall metabolic health, making them promising candidates for functional food applications in diabetes management[39-43].

POTENTIAL APPLICATIONS OF FERMENTED CORN STARCH AS PREBIOTICS IN THE MANAGEMENT OF T2D

Prebiotics have shown potential in managing T2D by modulating gut microbiota composition and improving metabolic outcomes. Prebiotics, including resistant starch, inulin, and oligofructose, have shown beneficial effects on glycemic control, cardiovascular markers, and inflammatory biomarkers in T2D patients. These substances promote the growth of beneficial bacteria, such as Bifidobacterium, while reducing harmful bacteria associated with T2D. The mechanisms of action involve reducing pro-inflammatory cytokines, decreasing intestinal permeability, and lowering oxidative stress[44-46]. Clinical studies affirm these benefits: F-Biotic^™, containing 60% resistant starch, significantly reduce fasting and postprandial glucose in metformin-treated patients[47], while MSPrebiotic^® improves glycemic and insulin parameters in older adults[48]. A systematic review of 27 studies further supports the efficacy of resistant starch, resistant dextrin, and oligofructose-enriched inulin in improving glycemic control and cardiometabolic risk markers[46]. Moreover, resistant starch 2 supplementation in women with T2D led to notable reductions in glycated hemoglobin A1c, tumor necrosis factor-α, and triglycerides, alongside increased high-density lipoprotein levels[49]. Fermented corn starch has been reported as a good source of resistant starch, resistant dextrin, IMO, maltodextrins, and gluco-oligosaccharides, which have been reported for their prebiotic properties in T2D (Table 1)[50-52]. These findings underscore the therapeutic potential of fermented corn starch as potential prebiotics in T2D management.

POTENTIAL APPLICATION OF FERMENTED CORN STARCH AS PROBIOTICS IN THE MANAGEMENT OF T2D

Probiotics have shown promising potential in managing T2D through various mechanisms. Probiotic interventions can improve glycemic control, reduce glycated hemoglobin A1c levels, and enhance glucose tolerance in T2D patients and animal models (Table 2). Probiotics, particularly Lactiplantibacillus and Bifidobacterium strains, can modulate gut microbiota composition, reduce intestinal permeability, and lower circulating lipopolysaccharides and inflammatory cytokines. These effects contribute to improved β-cell function, reduced inflammation, and better metabolic outcomes. Additionally, probiotics have been associated with improvements in lipid profiles and oxidative stress markers[53-55]. While the use of probiotics in T2D management shows promise, further research is needed to address remaining questions regarding optimal probiotic forms, dosages, and specific strains for maximum efficacy[56]. Probiotic potentials of isolated microorganisms from fermented corn starch in the management of T2D is shown as Table 2[57-63].

POTENTIAL APPLICATION OF FERMENTED CORN STARCH AS POSTBIOTICS IN THE MANAGEMENT OF T2D

Postbiotics, bioactive compounds derived from food-grade microorganisms, show potential in managing diabetes and other health conditions. These compounds include metabolites, SCFAs, cell fractions, and extracellular polysaccharides, which can have immunomodulatory effects and relieve symptoms in various diseases[64,65]. Fermented dairy products, particularly those containing LAB, may protect against cardiometabolic diseases through the release of bioactive peptides that influence glucose regulation and anti-inflammatory pathways[66]. Enzymatically modified corn starch can affect human fecal fermentation profiles, with different modifications leading to varying levels of digestibility and microbial metabolite production. Amyloglucosidase-treated starch, for instance, results in the highest production of short- and branched-chain fatty acids by gut microbiota[67]. The postbiotic potential of fermented corn starch in the management of T2D is shown as Table 3[68-71].

SETBACKS IN THE USE OF FERMENTED CORN STARCH IN TRIAD GUT-BIOTICS

Fermented corn products serve as dynamic ecosystems for diverse microorganisms, encompassing both beneficial and hazardous species. Spontaneous corn fermentation fosters the proliferation of LAB, yeasts, and molds, which drive essential biochemical transformations influencing flavor, texture, and nutritional value[72]. However, alongside these beneficial microbes, pathogenic contaminants can emerge, posing significant health risks. Notably, Staphylococcus aureus and Clostridium bifermentans, both capable of producing enterotoxins, have been detected in fermented corn starch, with implications for foodborne illnesses ranging from mild GI distress to severe intoxications[72]. The mycological profile of fermented corn is equally concerning, as Fusarium spp. and Aspergillus spp. synthesize fumonisins and aflatoxins, highly toxic secondary metabolites with carcinogenic and hepatotoxic properties. Similarly, Penicillium spp. is a known producer of ochratoxins, compounds linked to nephrotoxicity and neurotoxicity, exacerbating the health risks associated with fungal contamination[73,74]. Bacterial contaminants further complicate the safety of fermented corn products. Bacillus cereus, a spore-forming pathogen, generates heat-resistant enterotoxins responsible for emetic and diarrheal syndromes, while pathogenic Escherichia coli strains can trigger life-threatening conditions such as hemolytic uremic syndrome[75]. Compounding these concerns, inconsistencies in fermentation protocols lead to unpredictable fluctuations in bioactive compound concentrations, undermining efforts to establish reproducible therapeutic effects[76]. Consequently, the microbiological safety and biochemical consistency of fermented corn products remain critical challenges, necessitating stringent monitoring and standardization strategies to mitigate health risks.

LIMITATIONS

The findings of this review are constrained by several limitations which impede their applicability and clinical significance. Firstly, much of the data discussed stems from in vitro experiments and in vivo models, with a notable absence of robust, well-powered clinical trials specifically investigating fermented corn starch in the context of T2D. This gap limits confidence in translating preclinical findings into real-world therapeutic applications. Secondly, the long-term metabolic and microbiota-related impacts of fermented corn starch-derived interventions remain poorly understood. There is insufficient evidence on whether these effects are sustainable, safe, or beneficial over extended periods, underscoring the need for longitudinal human studies to assess durability, host-microbiota dynamics, and potential risks. Moreover, while the mechanisms by which fermented corn starch modulates gut microbiota and improves metabolic outcomes have been described, they warrant deeper critical analysis. In particular, it remains unclear whether these effects are strain-specific, host-dependent, or reproducible across diverse microbial ecosystems. Furthermore, inconsistencies across the literature, particularly concerning the bioavailability of postbiotic metabolites, the extent of glycemic control, and the variation in metabolic endpoints underscore the complexity of interpreting findings without standardized fermentation protocols or uniform microbial sources.

CONCLUSION

This review highlights the promising antidiabetic potential of microbiota-targeted compounds, prebiotics, probiotics, and postbiotics, derived from fermented corn starch. Evidence from in vitro, in vivo, and clinical studies demonstrates that these bioactive components can significantly improve glycemic control, insulin sensitivity, and inflammatory status through gut microbiota modulation and metabolic regulation. Resistant starch, IMO, and resistant dextrin, among others, show marked potential in lowering fasting glucose and enhancing incretin responses. Likewise, specific probiotic strains such as Lactiplantibacillus fermentum, Bifidobacterium breve, and Saccharomyces cerevisiae, along with postbiotics like SCFAs and exopolysaccharides, exhibit multifaceted benefits in reinforcing gut barrier integrity and mitigating metabolic dysfunctions associated with T2D. However, the field is hindered by limitations including scarce clinical studies focused on fermented corn starch, lack of standardized fermentation protocols, and safety concerns related to microbial contamination and mycotoxin production. These setbacks underscore the need for stringent quality control, microbial profiling, and fermentation optimization. To advance the therapeutic potential of fermented corn starch, future research should prioritize well-designed, placebo-controlled clinical trials, explore strain-specific mechanisms of action, and invest in fermentation technologies that ensure safety, consistency, and scalability. Integrating fermented corn starch-based interventions into precision nutrition strategies holds great promise for sustainable, food-based solutions in the management and prevention of T2D.