Introduction

Rapid urbanization has been a critical feature of India's development. People have increasingly migrated from rural areas to cities for better economic opportunities. This shift has led to changes in living conditions, employment patterns, and social dynamics. Modern dietary changes, sedentary lifestyle, stress and anxiety, increased usage of certain medications, and deteriorating environmental conditions have adversely affected the gastrointestinal health of the world's population. These changes and new adaptations have been significantly affecting digestive health and the gut-brain axis causing diverse gastrointestinal disorders like Irritable Bowel Syndrome, Inflammatory Bowel Disease, Gastritis, Celiac disease, Diverticulitis, etc.

One such disease is Irritable Bowel Syndrome (IBS). IBS is a condition characterized by abdominal pain, bloating, or other discomfort occurring in association with a disturbed bowel pattern in the absence of organic causes that routine medical tests can detect. A growing number of people suffer from IBS, with an estimated 5.8%-17.5% prevalence, especially in females. IBS causes a tremendous decline in the health-related quality of life and brings a considerable socioeconomic burden of up to $19 billion. IBS can be diagnosed using Rome III criteria and subclassified according to patients' predominant stool pattern using the Bristol Stool Form Scale as either constipation- or diarrhea-predominant, mixed type, or unsubtyped/unclassified (i.e, insufficient abnormality of stool consistency to meet criteria for the other IBS subtypes; ). Up to 40% of patients with IBS have diarrhea as the predominant bowel symptom (IBS-D subtype). There are 4 different subtypes in IBS which are as follows:

Probiotics:

Probiotics, live microorganisms with health benefits, are commonly found in yogurt, fermented foods, supplements, and beauty products. They comprise various microorganisms, including Lactobacillus, Bifidobacterium, and Escherichia coli groups.

These microorganisms offer several advantages, like modulating the immune response in the gastrointestinal tract and balancing microbial populations, inhibiting harmful organisms. Probiotics are proven to be safe and effective for patients with irritable bowel syndrome (IBS), enhancing stool frequency, transit time, and consistency. Consequently, they significantly enhance the quality of life for IBS patients.

Orally administered probiotics are now a preferred method, providing a promising option for treating intestinal disorders. Advancements in understanding their mechanisms have paved the way for designing new probiotic strains. Genetic engineering allows not only for strengthening existing strains but also for creating novel probiotics. These can include not only bacterial components but also regulatory systems or enzymes from human sources. If developed with meticulous attention to biological safety, genetically modified probiotics have the potential to revolutionize digestive health.

Quorum sensing

Quorum sensing (QS) is a communication process among bacterial cells, which includes the creation, detection, and response to external signaling molecules known as Autoinducers (AIs). These AIs build up as bacterial populations grow, and bacteria use this information to detect variations in their cell numbers. This enables them to adjust gene expression collectively. QS regulates genes that coordinate activities advantageous for bacteria when performed collaboratively. These activities include bioluminescence, sporulation, competence, antibiotic production, biofilm formation, and the secretion of virulence factors.

Pseudomonas aeruginosa also uses quorum sensing to communicate with other cells. The las system in P. aeruginosa consists of the LasR transcriptional regulator and the LasI synthase protein. LasI is essential for the production of the AHL signal molecule N-(3-oxododecanoyl)-l-homoserine lactone (3O-C12-HSL). LasR requires 3O-C12-HSL in order to become an active transcription factor.

Serotonin has the ability to function as a quorum-sensing molecule in bacteria through the LasR/LasI pathway. Serotonin triggered a response from the cellular quorum-sensing system, las QS, at concentrations measured in micromoles per liter (μM). This discovery is particularly significant because typical serotonin levels in the digestive tract range from 10 μM in healthy individuals to approximately 100 μM in those with diseases. Elevated serotonin levels in Inflammatory Bowel Disease (IBD) patients, coupled with its ability to activate quorum-sensing pathways, offer promising avenues for improved patient care and therapeutic interventions.

Melatonin Biosynthesis

The production of melatonin from tryptophan involves a sequence of reactions, namely 5-hydroxylation, decarboxylation, acetylation, and transmethylation. These reactions occur in a species-specific order. Our project adopts the melatonin biosynthesis pathway depicted in Figure 1, based on previous studies related to serotonin production from tryptophan and melatonin synthesis from serotonin. Initially, tryptophan decarboxylase (TDC) transforms tryptophan into tryptamine. Tryptamine is then converted into serotonin by tryptamine 5-hydroxylase (T5H). Following this, serotonin N-acetyltransferase (SNAT) catalyzes serotonin into N-acetylserotonin (NAS). Lastly, N-acetylserotonin undergoes modification into melatonin through the action of caffeic acid O-methyltransferase (COMT).

References

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