The Gut Microbiome and Diabetes: A Review of Current Understanding and Therapeutic Implications

Waghamare Suresh^*

Department of Pharmaceutics at NIMS Institute of Pharmacy, NIMS University, Jaipur, Rajasthan, India–302131.

Received:25 May 2025; Accepted:28 Aug 2025; Published:5 Sep 2025

Citation:Waghamare Suresh.“The Gut Microbiome and Diabetes: A Review of Current Understanding and Therapeutic Implications” J Diabet Clin Endocrinol (2025): 108. DOI: 10.59462/JDCE.3.1.108.

Copyright: © 2025 Waghamare Suresh..This is an open-access arti­ cle distributed under the terms of the Creative Com­mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

This review investigates the critical role of the gut microbiome in maintaining metabolic homeostasis and its involvement in the onset and progression of both Type 1 and Type 2 diabetes (T1D and T2D). It aims to elucidate the relationships between microbial composition, diversity, and function, and how these factors contribute to diabetic pathophysiology. An analysis of recent literature was conducted focusing on studies that examine gut microbial alterations in diabetic patients, mechanisms of microbiome-related metabolic changes, and therapeutic interventions. Emphasis was placed on interventions such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications. The findings reveal that dysbiosis—an imbalance in gut microbial communities is a common feature in both T1D and T2D. Dysbiosis contributes to disease development by promoting inflammation, impairing gut barrier function, and inducing insulin resistance. Several microbiome-modulating therapies have demonstrated potential in improving glycemic control and metabolic health. However, patient response varies significantly due to individual microbial and genetic variability. The gut microbiome is a crucial factor in the pathogenesis and management of diabetes. While microbiome-targeted therapies show promise, clinical application remains challenging. Future strategies should prioritize personalized approaches that consider individual microbiome profiles to optimize therapeutic outcomes.

Keywords:Gut microbiome, diabetes, therapeutic interventions, dysbiosis, Metabolic health

Introduction

Diabetes is rising globally, with worldwide prevalence of diabetes in adults in 2017 as 8.8% of the world's population, with a projected increase to 9.9% by 2045. Estimates are that in 2017, there were 424.9 million diabetics worldwide, and that by 2045, that number will increase by 48% to 628.6 million. Roughly 5%, 10%, 15%, and nearly 20% of the global population suffer from diabetes, respectively, in the age groups 35–39, 45–49, 55–59, and 65–69. Diabetes hits the "middle-aged" people between 40 and 59 years across the world with significant social and economic impacts. Further, diabetes most severely hits low- and middle-income countries. [1,2] Approximately 70–75% of patients with proven coronary artery disease, including those with acute myocardial infarction, have coincidental diabetes or disturbed glucose metabolism, i.e., close to 50% have overt diabetes. Of them, up to 20% are unknown, and an additional 25% have a pre- diabetes background on the gut microbiome. These nations harbour 77% of all individuals with diabetes globally. Apart from obvious diabetes, there are 352.1 million at risk of diabetes, or with established pre-diabetes, a figure that will rise to 531.6 million by 2045. Two thousand years earlier, Hippocrates declared, "All diseases begin in the gut," something properly linked to dysregulation of the immune system and disease susceptibility. [2,3,4,5,6]

The gastrointestinal tract contains a rich and unique group of microorganisms that make up the gut microbiota. We are aware that diet can alter the gut microbiota and potentially affect metabolism [7]. When the gut microbiota shifts in terms of Bacterial content, or dysbiosis, it has a propensity to predispose to inflammation, which studies prove to be the beginning of disrupted gut homeostasis in patients with diabetes. The gut microbiome and changes in the gut microbiome before and after consumption of supplements, dietary Modification, anti-diabetic drugs, and fecal microbial transplantation was relevant, given that the Composition of the intestinal microbiota has been proven to influence host metabolism and lead to aberrant blood glucose control [8]. Diet plays a pivotal role in shaping the gut microbiota, with significant implications for metabolic health. A high-fat, low-fiber diet promotes gut dysbiosis an imbalance in microbial populations— marked by an increase in pro-inflammatory bacteria and a decline in beneficial microbes. This dysbiosis leads to greater intestinal permeability and reduced insulin sensitivity, ultimately contributing to chronic inflammation and insulin resistance. Conversely, diets rich in fiber, prebiotics, and probiotics help maintain microbial balance, reduce inflammation, and improve metabolic function. As shown in (Figure 1), these gut-mediated mechanisms critically link dietary patterns with the pathogenesis of type 2 diabetes (T2D) [9].

Since several therapy interventions are aimed at the microbiota, there exists a two-way relationship between the gut microbiota and diabetes. Synthesis of amino acids, short-chain fatty acid (SCFA) production, nutrient absorption, prevention of colonization by pathological Bacteria, regulation of bile acid composition, and production of various pattern recognition molecules are all mechanisms by which the gut microbiota plays roles in health and disease. This systematic review targets the development of low-grade inflammation involving the gut microbiota and explores possible pathogenesis and therapeutic interventions in handling diabetes [10].

The overall view of this review is to assess knowledge on the correlations between gut microbiota and diabetes and uncover new therapeutic agents with the potential to influence the microbiota, as there is a distinct correlation between gut microbiota and diabetes. The aim of this systematic review, in accordance with Preferred Reporting Items conducted for Systematic Reviews and Meta-analyses (PRISMA) 2020, was to establish the effectiveness and benefits of therapeutic targets for Type 2 diabetes at the gut microbial level. We gathered and analyzed articles, such as clinical trials, literature reviews, systemic reviews, and meta-analyses between 2012 and 2022 [11,12].

The Gut Microbiome: Composition and Function

Bacteria, viruses, fungi, and parasites that constitute the gut microbiome. Differences in the composition of gut microbiota among individuals can be explained by dietary reasons. Firmicutes and Bacteroidetes are the two largest types of the six phyla which constitute the gut microbiota, the other two being Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia. The four best-studied fungus (gut mycobiota) are Cladosporium, Saccharomyces, Candida, and Malassezia.Microorganisms known as bacteria: The most common bacteria in the gut, including Clostridium, Ruminococcus, and Eubacterium the second most common form of bacteria in the gut are known as Bacteroidetes. Of the actinobacteria is the genus Bifidobacterium [11].

The most dominant phylum of the gut microbiome is Proteobacteria. One of the most dominant phyla of the gut microbiome is Fusobacteria. The major phylum of the gut microbiome is Verrucomicrobia. Fungi are Cladosporium, Saccharomyces, Candida, and Malassezia.

The trillions of bacteria and other microscopic organisms that live in the human intestinal tract are called the gut microbiota. Their environment is called the microbiome. Most of the body's bacteria are helpful, but when they become out of balance, they can be harmful. The terms microbiota and microbiome are often confused with one another. This is however not true. A variety of bacteria, viruses, fungus, and other microbes that inhabit a region, such as the human gut, constitute the microbiota. The collective term "microbiome" is used to describe the entire environment of the body, including its microbes, genes, and environmental factors. This article discusses the differences between the microbiota and microbiome [13]. Human health is also strongly influenced by the big and complex population of bacteria called the gut microbiota. The gut microbiota, formerly referred to as the gut microflora, plays a vital role in maintaining several essential physiological functions. These include gaining energy from digested food, fighting off infections, regulating the immune system, and supporting the intestinal and gut biochemical barriers [14]. These processes can be significantly influenced by alterations in the composition of the microbiome (Table 1).

Although the gut harbors beneficial bacteria, it is also susceptible to infections by pathogenic bacteria, particularly within the gastrointestinal tract. Such infections may result in food poisoning and gastrointestinal diseases, often characterized by symptoms such as vomiting and diarrhea.

Table 1:Role and Impact of Gut Microbiota on Human Health

Gut Microbiome and Type 1 Diabetes (T1d)

Type 1 diabetes (T1D) is a long-term autoimmune disease in which the immune system inaccurately targets the insulin-producing beta cells within the pancreas. Increasing amounts of evidence imply that the gut microbiota the complex community of microorganisms that live in the gastrointestinal tract is critical in T1D development and pathology. The gut microbiota communicates with the immune system of the host and is believed to modulate autoimmune responses [31].

One of the most important functions of the gut microbiota is to facilitate the maturation and control of the immune system. One of the most important parts of the immune system, the Gut-Associated Lymphoid Tissue (GALT), is in direct contact with the microbiota and allows for immune education. A healthy microbiome induces immune tolerance to non-pathogenic antigens and avoids uncontrolled immune activation. On the other hand, dysbiosis microbial community imbalance can induce inflammation and immune dysregulation, leading to the development of autoimmune conditions such as T1D [32]. Research has confirmed that people with T1D tend to have their gut microbiota composition modified compared to non-diseased humans. These include decreased microbial diversity and increased levels of pro-inflammatory bacteria. For instance, changes in the ratio between Firmicutes and Bacteroidetes have been reported, which may be responsible for immune dysregulation and metabolic derangements of diabetes. Modulation of the immune system is the central emphasis in the prevention or therapeutic intervention of T1D. [33], [34] Strategies are geared towards preventing the immune system from attacking pancreatic beta cells by inducing immune tolerance. Such strategies involve immunosuppressive agents, vaccines, and cell-based therapies that are aimed at modulating T-cell responses. Restoring gut microbial balance using probiotics, prebiotics, and dietary therapy is also being explored as a potential method of modulating the immune system and possibly preventing or delaying the onset of T1D. (Figure2) [34, 35].

Figure 2.Gut Microbiome and T1D Relationships

Gut Microbiome and Type 2 Diabetes (T2d)

Type 2 diabetes (T2D), a metabolic syndrome that is defined by insulin resistance and chronic inflammation, is also deeply modulated by the gut microbiota. The microbiota modulates metabolic health through various mechanisms such as the production of short-chain fatty acids (SCFAs), lipopolysaccharide (LPS) release, and control of gut permeability.

1. SCFA Production:
The gut bacteria ferment dietary fiber to yield SCFAs like acetate, propionate, and butyrate. These SCFAs confer numerous metabolic advantages. Butyrate, especially, improves insulin sensitivity by stimulating G-protein-coupled receptors (GPR41 and GPR43), which induce the secretion of hormones such as glucagon-like peptide 1 (GLP-1) that control blood glucose. SCFAs also have anti-inflammatory action by decreasing the activation of nuclear factor kappa B (NF-κB) and hence chronic low-grade inflammation commonly linked to T2D. Butyrate also promotes intestinal health by acting as the main source of energy for colonic epithelial cells and upholding gut barrier function [37].
2. LPS (Lipopolysaccharide) and Inflammation:
LPS, a constituent of the outer membrane of Gram-negative bacteria, may translocate into the systemic circulation when the intestinal barrier is intact, a state referred to as "leaky gut." This translocation leads to metabolic endotoxemia, which causes systemic inflammation. LPS stimulates the immune system and results in the release of pro-inflammatory cytokines like TNF- α, IL-6, and IL-1β. These cytokines disrupt insulin signaling in tissues such as muscle and adipose tissue, hence enhancing insulin resistance. LPS also stimulates Toll-like receptor 4 (TLR4), which triggers chronic inflammatory cascades involved in the pathogenesis of T2D [38].
3. Gut Permeability and Metabolic:
Increased intestinal permeability, or "leaky gut," causes bacterial toxins and metabolites to enter the bloodstream, inducing systemic inflammation. This compromised gut barrier function is often seen in people with T2D. The ensuing immune activation promotes insulin resistance by interfering with normal insulin receptor function. Thus, the uptake of glucose into cells is compromised, adding to hyperglycemia and the development of T2D [39].
4. Interactions between Gut Microbiome and Insulin Resistance
Dysbiosis microbial imbalance in the gut is prevalent in individuals with T2D. Studies report that higher numbers of pro-inflammatory bacteria and lower numbers of beneficial microbes lead to insulin resistance and chronic inflammation. Diet has a fundamental influence on the gut microbiota. High-fat, low-fiber diets correlate with dysbiosis, greater gut permeability, and higher systemic inflammation. On the contrary, fiber-containing diets supplemented with prebiotics and probiotics support a balanced gut microbiota, decrease inflammation, and enhance insulin sensitivity [40].

Therapeutic Implications of Modulating the Gut Microbiome

The gut microbiome has emerged as a crucial player in the pathophysiology of both type 1 diabetes (T1D) and type 2 diabetes (T2D). Growing evidence indicates that targeted modulation of gut microbial communities can offer significant therapeutic potential for the prevention and management of these metabolic disorders. Strategies such as probiotics, prebiotics, dietary interventions, fecal microbiota transplantation (FMT), and pharmacological modulation are currently being investigated for their capacity to restore microbial balance, reduce systemic inflammation, and enhance metabolic regulation [41].

Probiotics and Their Role in Diabetes Management

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host by improving gut microbial composition and function. Probiotic strains such as Lactobacillus and Bifidobacterium are well-studied for their ability to enhance intestinal barrier integrity, inhibit the growth of pathogenic bacteria, and modulate immune responses. These actions contribute to the reduction of endotoxemia and low-grade inflammation, key features in the pathogenesis of T2D. Additionally, probiotics promote the production of short-chain fatty acids (SCFAs), particularly butyrate, which exerts anti-inflammatory effects and enhances insulin sensitivity. Some strains also show promise in modulating immune activity, potentially influencing autoimmune processes involved in T1D. Overall, probiotics represent a promising adjunctive therapy for metabolic regulation in diabetes management.

Prebiotics: Feeding the Gut for Better Glucose Control

Prebiotics are non-digestible food components that selectively stimulate the growth and activity of beneficial gut bacteria. Common examples include inulin, fructose oligosaccharides (FOS), and galacto oligosaccharides (GOS). These compounds are fermented by colonic bacteria, leading to increased SCFA production, particularly propionate and butyrate, which are known to improve glucose metabolism and reduce inflammation. Prebiotics have shown efficacy in reducing insulin resistance, modulating lipid profiles, and enhancing satiety, thereby indirectly assisting in glycemic control. Furthermore, prebiotics can influence gut-derived hormonal pathways such as glucagon-like peptide-1 (GLP-1), contributing to improved glucose homeostasis. The combined use of probiotics and prebiotics as synbiotics may provide synergistic benefits in modulating the gut microbiota and ameliorating metabolic dysfunction [42].

Dietary Interventions: Shaping the Microbiome through Nutrition

Diet is a fundamental and modifiable factor that significantly influences the composition and function of the gut microbiota. Diets rich in dietary fiber, particularly those following Mediterranean or plant-based patterns, have been associated with increased microbial diversity and SCFA production. Such dietary patterns are linked to decreased intestinal permeability, lower systemic inflammation, and improved glycemic control. Conversely, Western-style diets characterized by high intakes of refined sugars, saturated fats, and low fiber content promote gut dysbiosis and metabolic endotoxemia, exacerbating insulin resistance and hyperglycemia. Personalized dietary strategies based on individual microbiome profiles have shown promise in tailoring interventions that maximize therapeutic outcomes. Nutritional modulation of the gut microbiota thus represents a sustainable and non-pharmacological approach to diabetes prevention and treatment [43].

Fecal Microbiota Transplantation (FMT): A Novel Microbiome Reset

Fecal microbiota transplantation (FMT) involves the transfer of fecal material from a healthy donor to a patient with the aim of restoring gut microbial balance. Initially established for the treatment of recurrent Clostridium difficile infections, FMT is now being explored for metabolic disorders, including T2D and metabolic syndrome. Preliminary studies have demonstrated improvements in insulin sensitivity and glycemic control following FMT from lean donors to individuals with obesity or T2D. The beneficial effects are thought to be mediated through the introduction of favorable microbial taxa and restoration of metabolic pathways disrupted in diabetic patients. However, the clinical application of FMT in diabetes is still in its infancy, and concerns regarding donor screening, microbial transmission risks, and long-term efficacy must be addressed before widespread implementation [44].

Pharmacological Modulation of the Microbiome: A New Frontier

In addition to dietary and microbial therapies, pharmacological strategies targeting the gut microbiota have begun to gain attention. While broad-spectrum antibiotics can disrupt gut microbial homeostasis, newer therapeutic approaches are being developed to selectively modulate microbial activity without detrimental effects. Examples include bacteriophage therapy, which targets specific pathogenic strains, and SCFA analogs designed to replicate the beneficial effects of microbial metabolites. Furthermore, widely prescribed antidiabetic drugs such as metformin have been shown to exert part of their therapeutic effects via modulation of the gut microbiome, particularly by enhancing the abundance of Akkermansia muciniphila and other beneficial species. This highlights the bidirectional interactions between host pharmacology and the gut microbiota, suggesting that microbiome-targeted drug development may play an essential role in future diabetes therapies [45].

Advanced Insights into the Gut Microbiome: Metagenomics, Metabolomics, and Implications for Diabetes and Human Health

Information from large prospective cohort studies and extensive metagenomic sequencing with strain resolution has been obtained to truly represent interindividual heterogeneity, dynamics, and demographic variation in the human gut microbiome (GM). The method enables the detection of robust disease-associated microbial signatures and their interactions with dietary history.

Intense associations between human health and gut bacteria are probably not adequately described using the high-level taxonomic information that is supplied by 16S rRNA gene sequencing. An increasingly strong focus is on boosting the proportion of GM sequence reads with projected functions assembled into metagenomes. A recent global review of all publicly available metagenomes from 31 nations on six continents identified that around 70% of genomes isolated from fecal samples remain uncharacterized. These genomes code for more than 170 million protein sequences, of which more than 40% have no functional annotation [46].

It is critical to expand our knowledge of the roles of fungi, viruses (e.g., bacteriophages), and bacteria in diabetes. The significance of these GM inhabitants and their exchanges with bacterial strains for diabetes has only been superficially investigated. Determining proteins, peptides, and chemical compounds generated through co-metabolic activities of gut microbes with the host that influence human host biology is a primary objective. While some diabetes-related metabolites have been characterized, the complete range of molecules producible by the GM is unknown [47].

It is important to clarify how the gut microbiota, its metabolites, and gut/plasma proteins are involved in the sequence of pathophysiological events behind diabetes and associated disorders. Several GM-derived metabolites, such as those derived from aromatic amino acids, have been implicated in cardiovascular endpoints, but the physiological functions of most remain unclear. A further priority is determining the modifiability of diabetes-related GM signatures using interventions like fecal microbiota transplantation (FMT), diet, probiotics, or supplementation with metabolites in order to prevent or reduce disease. Elucidation of synergistic, complementary, or antagonist roles of GM with respect to antidiabetic medications is critical for assessing therapeutic effectiveness and mechanisms [48].

The genomic revolution has the capacity to revolutionize patient care through the personalization of treatments, lowering the rate of adverse events, and decreasing healthcare expenditures. Early advancements in this area were a result of the use of human genome sequencing to maximize cancer prevention and treatment methods. Now that it is possible to describe the microbiome comprising all microbes that inhabit and reside on the human body along with their genetic components using next-generation sequencing (NGS), we can make use of this important component in creating new preventive and therapeutic approaches [49]. The microbiome's importance spans multiple aspects of human disease, including pathogenesis, phenotype, prognosis, and treatment response, and it serves as a potential diagnostic and therapeutic biomarker. This review highlights the importance of NGS in characterizing microbial populations and their functions, as well as accurately identifying microorganisms in infectious diseases [50].

New Technologies in the Study of the Gut Microbiome: Metagenomics and Metabolomics

The gut microbiota profoundly influences human health, affecting immunity, digestion, and even mental health. Emerging technologies such as metagenomics and metabolomics have revolutionized our ability to study and understand this complex microbial environment. Metagenomics, which sequences the genomes of all microorganisms in a sample, eliminates the need to culture individual species. This approach enables comprehensive identification of microbial diversity, relationships, and functions. Researchers can identify pathways related to immune regulation, disease resistance, and nutrient metabolism by analyzing microbial genes. Advanced techniques like shotgun metagenomics allow for the detection of rare species and strain- level differences, which are crucial for personalized medicine [51].

Metabolomics is the study of small molecules, metabolites, and biochemicals that represent the chemical fingerprints of microbial activity. These metabolites play essential roles in energy production, host-microbe interactions, and cell signaling pathways. Tools such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy help map this biochemical landscape and offer insights into the effects of diet, antibiotics, and probiotics on the microbiome [52,53].

The integration of metagenomics and metabolomics holds tremendous clinical potential. Metagenomics can identify dysbiosis linked to diseases like diabetes, obesity, and inflammatory bowel disease (IBD), while metabolomics can discover biomarkers that indicate disease progression or treatment efficacy [54].

Conclusion

Diabetes is increasingly becoming a major global health concern, with estimates predicted to increase from 424.9 million in 2017 to 628.6 million by 2045, particularly in middle-aged adults in low- and middle-income countries. The gut microbiota, a constellation of bacteria, fungi, viruses, and parasites, plays a crucial role in metabolic control, immune function, and disease prevention. Dysbiosis, a state of microbial imbalance, correlates with chronic inflammation and is a key player in the pathogenesis of both type 1 (T1D) and type 2 diabetes (T2D). Dysbiosis in T1D can delay immune tolerance, culminating in autoimmune beta-cell destruction. In T2D, dysbiosis induces insulin resistance through various mechanisms, including reduced short-chain fatty acid (SCFA) production, increased gut permeability, and lipopolysaccharide (LPS)-induced inflammation. Some of the major bacterial phyla are Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Diet, antibiotics, and lifestyle can modulate the microbiota, which can be modified through interventions such as probiotics, prebiotics, dietary modifications, fecal microbiota transplantation (FMT), and drugs that act on the microbiome. Advanced technologies like metagenomics and metabolomics are enhancing our understanding of gut microbial diversity, their roles, and metabolic products. While these therapies hold promise for personalized diabetes treatment, challenges remain in standardizing treatment processes, determining long-term effects, and incorporating microbiome profiling into routine clinical care.

Acknowledgement:-appreciation is also extended to the faculty and staff of the Department of Pharmaceutics, NIMS Institute of Pharmacy, NIMS University, Jaipur, for their academic support and resources.

Conflicts:-Conflicts of the authors declare no conflicts of interest

Funding:-No specific funding was received for the preparation of this review article.

Authors Contributions:-Waghamare Suresh was responsible for the conceptualization, literature review, writing, and critical revision of the manuscript.

Source of Support:-Nil

Consent Statement:-Informed consent was obtained from all individual participants included in the study

Data Availability Statement:-The data presented in this study are available on request from the corresponding author

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