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Introduction

Importance of gut Microbiota in human health and disease

The gut microbiota refers to the complex and diverse community of microorganisms, including bacteria, viruses, fungi, and archaea, residing in the gastrointestinal (GI) tract. This microbial ecosystem plays a critical role in maintaining overall health, influencing various physiological processes, and interacting with the host’s immune system [10]. The gut microbiota is highly diverse and varies between individuals based on factors such as age, diet, genetics, and environment. The gut microbiota is predominantly composed of bacterial species from major phyla such as Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, cynobacteria, Verrucomicrobia healthy gut microbiota is characterized by a high degree of microbial diversity,[11]. Which is thought to contribute to resilience against disease and disturbances. The gut microbiota is a vital component of human health, contributing to digestion, metabolism, immune function, and overall well-being [12]. Understanding its complex interactions with the host and the impact of external factors such as diet and lifestyle is crucial for developing strategies to maintain or restore a healthy microbiota and prevent or manage chronic diseases. The gut microbiota performs numerous essential functions that contribute to host health. Microbes help digest complex carbohydrates, ferment dietary fibers, and produce short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate, which provide energy and support gut health[13]. Certain gut bacteria synthesize essential vitamins, such as vitamin K and some B vitamins, which are crucial for various metabolic processes[14]. The gut microbiota interacts with the immune system, helping to regulate immune responses and maintain a balanced immune environment. It plays a role in the development of immune tolerance and protection against pathogens. The gut microbiota helps maintain the integrity of the intestinal barrier, preventing the entry of harmful substances and pathogens into the bloodstream. The metabolism of dietary components by gut microbes results in the production of metabolites that can influence host physiology, including SCFAs that affect inflammation and metabolism[15]. Microbial interactions with the gut-associated lymphoid tissue (GALT) play a critical role in shaping immune responses and preventing autoimmune and inflammatory conditions. Gut microbes communicate with host cells through various signaling pathways, influencing gut motility, mood, and overall health. Diet and lifestyle factors have a profound impact on the composition and function of the gut microbiota. The intake of fiber-rich foods promotes beneficial microbial growth and diversity, while high consumption of processed foods and antibiotics can disrupt the microbial balance. Physical activity, stress, and sleep patterns can also affect the gut microbiota. The imbalance in the gut microbiota has been linked to a range of health conditions, including metabolic syndrome, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and even mental health disorders like depression and anxiety. Modulating the gut microbiota through dietary changes, probiotics, and fecal microbiota transplantation is being explored as potential therapeutic strategies for various health conditions [16].

The gut microbiota's makeup differs depending on the digestive tract's location. These microbes work together to maintain a balanced gut environment, support digestion, and contribute to overall health. The gut microbiome is highly diverse, and the specific composition can vary from person to person based on diet, lifestyle, and other factors [17].

Table 2. Outlining some beneficial microbes commonly found in the human gut, along with their general functions

Fig: Distribution of the normal human gut microbial flora

The rationale for studying ultra-processed foods is multifaceted, encompassing the need to understand their health impacts, inform dietary guidelines and policies, address social and economic factors, advance food science, enhance public awareness, and contribute to broader health research. Such studies are essential for developing effective strategies to mitigate health risks associated with UPFs and promote healthier eating habits, ultimately improving public health outcomes. Ultra-processed foods (UPFs) can influence several metabolic pathways in humans due to their specific nutrient composition, additives, and processing methods. Below is a table outlining the key metabolic pathways affected. Ultra-processed foods can influence several metabolic pathways in humans due to their specific nutrient composition, additives, and processing methods.UPFs typically contain high levels of sugars, unhealthy fats, and artificial additives, and lack dietary fiber, which is crucial for nourishing beneficial gut bacteria this can affect the overall microbial composition in the gut Some intestinal microbes,[18]particularly certain bacteria and yeasts can ferment available carbohydrates in UPFs. This process breaks down complex carbohydrates and sugars into simpler compounds, producing gases (CO₂ and CH₄) and short-chain fatty acids (SCFAs) as byproducts [19] this product cannot be digested easily by intestinal microbes and enzymes so it interferes with the digestion process and metabolic pathway in the gut,[20] table outlining the key metabolic pathways affected by UPFs.

Table 3. UPFs affect metabolic pathways along with the mechanisms and potential health impacts

Gut microbiota in human disorder

The gut microbiota plays a significant role in various disorders associated with the consumption of ultra-processed foods. The classification of microbiota related to these disorders highlights specific taxa that exhibit alterations in response to UPF consumption, contributing to conditions alterations in gastrointestinal microbiota that have been linked to several major human diseases, including obesity, diabetes, cardiovascular diseases, cancer, hypertension, and inflammatory bowel diseases (IBDs)[21]. Understanding these associations can aid in the development of targeted dietary interventions and therapeutic strategies. Several studies using epidemiological, physiological-based approaches, along with experiments, have the significant role of intestinal microbiota in both health and disease [21].  The term "dysbiosis" refers to changes in the composition of gut microbiota that are often observed in various diseases, [22]. Defining a healthy microbiome composition remains challenging due to significant inter-individual variability [23]. A balanced gut microbial community is crucial for establishing a mutually beneficial relationship between the host and its microbiome.

1. Obesity

Recent alterations in gut microbiota composition have been identified as significant factors in the development of obesity [24]. Certain gut microbiota species, often referred to as "obesogenic gut microbiota," include Firmicutes, Bacteroidetes, Rhizobium, Lactococcus, and Clostridium, all of which can play a substantial role in promoting obesity [25]. Specifically, these obesogenic microbes can contribute to weight gain by producing short-chain fatty acids (SCFAs) like butyrate, which provide additional energy to the host. Increased abundance of certain Firmicutes, particularly Faecalibacteriumprausnitzii, and Ruminococcus, is often observed in individuals with obesity. These microbes can enhance energy extraction from the diet. Additionally, metabolites produced by intestinal microbiota can induce low-grade inflammation, further complicating the obesity landscape [25] Furthermore, genetic factors and epigenetic variations significantly influence the relationship between gut microbiota composition and its role in obesity and metabolite production.

2. Diabetes Mellitus

Diabetes mellitus significantly impacts global health, with risk factors including family history, poor diet, and obesity. The rise in urbanization, dietary changes, and unhealthy lifestyles contribute to the increasing incidence of diabetes, making it a global crisis. About 422 million people worldwide have diabetes, the majority living in low-and middle-income countries, and 1.5 million deaths are directly attributed to diabetes each year.  Recent research indicates that diabetes progression is closely linked to changes in the intestinal microbiota composition [26]. Diet plays a crucial role in shaping the intestinal microbiota and is a significant factor in diabetes development [27]. Certain species of Bacteroides, such as Bacteroidesfragilis, may be associated with improved insulin sensitivity, while dysbiotic forms can contribute to insulin resistance and higher levels of Prevotella have been linked to metabolic dysregulation and inflammation, often seen in type 2 diabetes.

The influence of microbiota on type 2 diabetes is mediated through mechanisms involving changes in butyrate and in cretin secretions [28] In type 2 diabetes patients, studies have shown moderate intestinal microbial dysbiosis, a decrease in butyrate-producing bacteria, and an increase in opportunistic pathogens [28]. Other research highlights the significant impact of gut microbiota on type 2 diabetes pathways, including insulin signaling, inflammation, and glucose homeostasis [29]. However, further studies are needed to fully understand the mechanisms and the influential role of gut microbiota in diabetes development.

3. Cardiovascular Disease-Related Microbiota

Heart disease remains a leading cause of death worldwide, with its prevalence expected to rise, particularly in low and middle-income countries. The pathophysiology and progression of cardiovascular diseases (CVDs) also involve the intestines, mainly due to reduced blood flow leading to intestinal barrier dysfunction. The intestinal endothelial barrier is regulated by various mechanisms, including a well-balanced intestinal microbiota [30]. Recent studies have highlighted the role of intestinal microbiota in heart disease and stroke [31, 32]. Emerging evidence indicates that gut dysbiosis is linked to the production of numerous metabolites by intestinal microbiota, which disrupts the function of the gut endothelial barrier. Increased populations of Escherichia coli and other Enterobacteriaceae are often linked to inflammation and cardiovascular risk factors [33]. Faecalibacterium Reduced levels of Faecalibacteriumprausnitzii are associated with increased cardiovascular risk, possibly due to its anti-inflammatory properties[34].

4. Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease is prevalent in Western countries and is rapidly increasing in newly industrialized regions like Asia, the Middle East, Africa, and South America [35]. Recent advancements have highlighted the role of gut microbiota in the pathogenesis of IBD. Studies show that patients with IBD often have decreased diversity in their intestinal microbiota, particularly a reduction in Firmicutesand Proteobacteria[36]. This imbalance is linked to abnormal immune responses and various intestinal disorders. Consequently, modifying gut microbiota to restore immunological balance is being explored as a potential treatment strategy for IBD [37]. Alterations in the abundance of Clostridium species, particularly Clostridium difficile, can exacerbate IBD symptoms and are often found in dysbiotic states.

5. Hypertension-Related Microbiota

Hypertension is a threat to public health [38]. ‘Studies have shown that various genetic and environmental factors, including dietary salt intake, lack of exercise, and alcohol consumption, also contribute to hypertension progression [39]. Moreover, alterations in the composition of the intestinal microbiota can result in the development of novel antihypertensive therapies.’ ‘The various mechanisms underlying the relationship between gut microbiota and hypertension have been proposed, although there is no definite understanding.’ The ratio of Bacteroidetes and Firmicutes within intestinal microbiota has been significantly associated with hypertension [40]. Fusobacterium have been linked to hypertension and associated inflammatory processes[41]. Lactobacillus and Bifidobacterium Decreased populations of these beneficial bacteria may contribute to hypertension by influencing metabolic health and inflammation [42].

6. Cancer-Related Microbiota

Cancer ranks as the second leading cause of death worldwide [43]. Various factors, including exposure to pathogens, UV radiation, toxic substances, diet, and lifestyle, significantly influence cancer risk. The risk is primarily determined by the dosage, duration, and combination of these factors, along with the patient’s genetic background [44]. There is increasing interest in understanding the characterization and functionality of intestinal microbiota due to its complex relationship with the host [45]. Research has shown that disruption or alteration of gut microbiota plays a significant role in the development of colorectal cancer in both genetic and carcinogenic tumor genesis models [44]. Studies in metabolomics and metagenomics have highlighted the dual role of gut microbiota in reducing cancer risk and promoting tumor growth, as well as its impact on anti-cancer therapies [46]. Alterations in the abundance of these genera are observed in colorectal cancer, potentially influencing tumor development through inflammation and metabolism. Fusobacteriumnucleatum is specifically linked to colorectal cancer, elevated levels of this bacterium may promote tumorigenesis[47].