Gut Microbiota in Human Health And Disease: A Review of Therapeutic Opportunities.

Momin Sameer Abdul hai ;Dr.Preeti kulkarni

Gahlot Institute of Pharmacy, Navi Mumbai, Maharashtra

Correspondence:  sameermomin2021@gmail.com

DOI: https://doi.org/10.71431/IJRPAS.2026.5805    

 INTRODUCTION

The human microbiota is a dynamic environment that develops following birth. It is composed of microorganisms that reside on the surfaces and in the orifices of the body, engaging in reciprocal interactions with the host [1]. The gut microbiome is made up of various microorganisms, including viruses, archaea, and bacteria. It has many more microorganisms than the human intestine, with the stomach having 100 to 150 times as many. The gut microbiome also contains more genes than the human genome, comprising approximately 1,000 species and 7,000 types of bacteria. Key groups include Firmicutes, which have both gram-positive and gram-negative species like Clostridium, Eubacterium, and Lactobacillus, and Bacteroidetes, which contain Prevotella and Bacteroides [2-5]. The crucial role of host-microbe interaction part in both health and illness. Diversity of the gut microbiota is heavily reliant on a number of host variables, such as diet, age, environment, and human behavior. But diet is now regarded as one of the key elements (modifiers) in influencing the gut microbiome [6]. By strengthening a competitive barrier, the microbiota has a significant impact on the host's health. Metabolizing nutrients, regulating immunological reactions, and protecting against pathogens, engaging in neural communication [7]. Driven by the microbiome, therapy has become a revolutionary area in medicine. Making use of intricate relationships between microbial communities and the host's biological functions to deal with a variety of health issues [8]. Present therapeutic approaches include probiotics, fecal microbiota transplantation (FMT), and other therapies based on microbial metabolites have demonstrated varying degrees of success. But their clinical use is frequently limited by elements like the high cost. The complexity of microbial interactions, inter-individual variability of microbiomes, and big gaps in our mechanistic understanding of how these treatments work at the molecular level. At the molecular level. In addition, regulatory obstacles and the absence of uniform procedures increase the challenge. Hinder their widespread use in clinical practice. The pressing need for these changes is highlighted by these difficulties. The underlying mechanisms of the host-microbiome interaction must be discovered through sophisticated research. Interactions and improve microbiome-based therapies for more consistent and predictable results [9,11].Over the past several years, our understanding of the human microbiome has grown rapidly, thanks to major global research efforts. Two of the most important projects in this field are the European Metagenomics of the Human Intestinal Tract (MetaHIT) and the Human Microbiome Project (HMP), which is funded by the U.S. National Institutes of Health. These large-scale studies have aimed to map out the vast community of microorganisms living in and on the human body, especially in the gut. In July 2014, researchers took a big step forward by combining gut microbiome data from a total of 1,267 samples collected from 1,070 individuals. This included 760 samples from people in Europe through MetaHIT, 139 from the U.S. via the HMP, and 368 from Chinese participants involved in a diabetes-focused study. The result was a comprehensive gene catalog of gut microbes, containing approximately 9.8 million unique genes. This non-redundant list gave scientists an incredibly detailed look at the genetic diversity of microbes in the human gut, opening up new possibilities for understanding how these microorganisms influence health and disease across different populations and lifestyles [12,13,14].

Microbiome-targeted investigational therapies for IBD:

Restoring healthy microbiota

Fecal microbiota transplantation (FMT) is a treatment where stool from a healthy person is processed and transferred into the digestive system of someone with inflammatory bowel disease (IBD). This method has gained a lot of attention because it’s been very successful in treating infections caused by Clostridium difficile.

However, there are still challenges when it comes to using FMT consistently. Different studies use different methods—some use fresh samples, others frozen; some give a single dose, while others use pooled samples from multiple donors. This lack of standardization makes it hard to compare results across studies. It’s also harder to know which donor made the difference when mixed samples are used, and using more donors may increase the risk of passing along harmful bacteria like E. coli.

Because there are still many unknowns about how safe and effective FMT really is, researchers are starting to look into using more carefully selected groups of microbes instead. These targeted treatments aim to restore a healthy balance in the gut microbiome and reduce the inflammation linked to IBD [15,16.17.18,19,20].

Microbiome-based therapeutic approaches

Friendly microbes that have evolved alongside the human body help by making important nutrients like vitamin K and B vitamins. They also break down certain complex sugars (like glycosaminoglycans) and produce helpful substances such as short-chain fatty acids (SCFAs), secondary bile acids, and essential amino acids that the body needs.[21,22]

METHODS

Literature sources

We looked for research on gut microbiota-based treatments for autoimmune illnesses in the China National Knowledge Infrastructure (CNKI), Medline Complete, Pubmed, Web of Science, Sinomed, VIP Database, Wanfang Database, and EMbase. The retrieval time spans from the database's creation to October 1, 2023. We also looked through the Cochrane Library and ClinicalTrials.gov. The additional material table displayed the search technique.

Patients were diagnosed with autoimmune diseases based on recognized medical guidelines. These diseases include, but are not limited to, celiac disease, lupus (including lupus nephritis), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia, multiple sclerosis (MS), and systemic sclerosis. This also includes conditions like type 1 diabetes (T1DM), oral lichen planus (OLP), Crohn’s disease, and ulcerative colitis.

Intervention Methods
The experimental group was given probiotics, either on their own or combined with other treatments. The control group received treatment without probiotics. There were no restrictions on the type, amount, duration, or way the probiotics were taken.

Outcomes
The main outcomes measured were how well the treatment worked for the disease (using scores like SLEDAI, DAS28, and PASI), levels of inflammation, and any side effects.

Study Design
Only randomized controlled trials (RCTs) were included. There were no limits on how the randomization was done, the year the study was published, or the language of the study.

Exclusion Criteria
Studies were excluded if:

1. They were not the right type (e.g., reviews, animal studies, data analyses, or non-RCTs).
2. The disease studied or the treatment used didn’t match the criteria.
3. The outcome measures didn’t fit the inclusion requirements.
4. The control group also received probiotics.

Search and Screening Methods

1. Initial Screening: Two researchers separately reviewed the titles and abstracts of the studies found through the search. They excluded any non-clinical studies or those not related to treating autoimmune diseases with probiotics.
2. Further Screening: The full texts of the remaining studies were then reviewed based on the inclusion and exclusion criteria to decide which RCTs would be included. If the two researchers disagreed on any study, the issue was discussed with the whole research team to reach a decision.

3.      Quality Assessment and Data Extraction: The selected RCTs were evaluated using the Cochrane Risk of Bias Tool. This tool looks at potential bias in the studies, which may come from poor study design or sample limitations. Each item was rated as having a high risk of bias, unclear risk, or low risk. The software Reman 5.4 was used to create charts showing the percentage and summary of bias risk in the studies [23].

Microbe-based strategies in T2DM prevention and intervention:

Probiotics:

"Probiotics are tiny living organisms found in certain foods that are believed to provide health benefits to both humans and animals” [24]. Recent studies show that eating foods rich in probiotics can help lower blood sugar levels, improve how the body responds to insulin, and reduce long-term blood sugar markers like HbA1c. Probiotics may also help control cholesterol, lower body weight, and improve fat metabolism. For example, a review of 30 clinical trials found that people who took probiotics had better blood sugar and insulin levels than those who didn’t [25,26].

Prebiotics:

Prebiotics are small carbohydrate molecules like oligofructose, oligogalactose, inulin, lactulose, and marshmallow sugar. The human body can’t digest them, but probiotics in the gut can use them as food [27]. When fermented, prebiotics help produce beneficial acids and support the growth of healthy bacteria. Several clinical studies have shown their positive effects on health. Diets high in prebiotics can help lower body weight, reduce fat, and improve how the body handles insulin. Some prebiotics that may help with diabetes or obesity include fructo-oligosaccharides, inulin, resistant dextrin, galacto-oligosaccharides (GOS), konjac fiber, beta-carotene, and plant-based dietary fiber. In one 12-week study, teenagers with Type 1 Diabetes who took inulin enriched with oligofructose had lower C-peptide levels and more bifidobacterial in their gut. Another 16-week study showed that the same supplement helped reduce weight, BMI, and inflammation (measured by IL-6) in overweight or obese teens, while also increasing healthy gut bacteria [28,29,30].

Synbiotics:

Prebiotics are often combined with probiotics in a product called Synbiotics. This combination isn’t just a mix of both ingredients—prebiotics are added in a way that helps probiotics grow and thrive both in the product and in the gut. Together, they work to create a healthier environment in the digestive system. Many clinical studies have shown that probiotics and prebiotics can help treat obesity and diabetes [31,32]. However, synbiotics are not used very often. This may be because prebiotics, which serve as food for probiotics, are not easily digested or absorbed by the human body. Instead of being digested, prebiotics are fermented by probiotics in the gut, helping good bacteria like Bifidobacteria and Lactobacilli grow. Since probiotics can be easily weakened or destroyed, combining them with prebiotics like inulin or resistant starch can protect them and improve their effects in the body. For example, a clinical trial with 102 people showed that taking a synbiotic supplement with Lactobacillus, β-carotene, and inulin for six weeks led to better insulin resistance and improved fat metabolism in patients with type 2 diabetes [33,34,35,36,37].

Fecal microbiota transplantation (FMT) :

Fecal microbiota transplantation (FMT) is believed to quickly bring back a healthy balance of gut bacteria. It works by fixing imbalances in the gut microbiome, strengthening the gut barrier, and boosting the production of short-chain fatty acids, which are important for keeping the intestinal lining healthy. MT is a well-known and effective treatment for recurring Clostridium difficile infections (CDI). Because it works well, is fairly safe, and gut bacteria seem to affect many other health problems, researchers are now studying how FMT might help treat other digestive and non-digestive diseases [38,39].

Gut Dysbiosis in Specific Human Disease Subtypes

Gut Imbalance in Different Diseases

Digestive Disorders

Because gut bacteria live right next to our intestines, any shifts in their makeup can have a big impact.

Inflammatory Bowel Disease (IBD):

• Crohn’s Disease (CD): People with CD often lose many helpful microbes like Faecalibacterium prausnitzii and Bacteroides, and instead have more harmful types like Adherent-Invasive E. coli and certain Proteobacteria. This imbalance helps fuel ongoing inflammation and impaired gut lining repair.[40,41,42]
• Ulcerative Colitis (UC): Similar losses of good bacteria happen here, but there’s often a bigger drop in butyrate-producing Clostridiales and an increase in mucin-eating bacteria like Ruminococcus gnavus. This makes inflammation worse and damages the gut barrier.[40,41]

Irritable Bowel Syndrome (IBS):

• IBS with Diarrhea (IBS-D): These patients often have changes in bile acid breakdown and more Ruminococcaceae, with lower Bifidobacteria. This combination speeds up gut movement and may worsen symptoms [43].
• IBS with Constipation (IBS-C): Here, there’s usually less overall gut diversity and more methane-producing archaea (like Methanobrevibacter smithii), which can slow things down and cause bloating [43,44].

Clostridioides difficile Infection (CDI):
Broad-spectrum antibiotics wipe out protective microbes, creating space for C. difficile to grow and produce toxins. Many people with CDI suffer repeated infections because their gut never fully recovers its healthy microbiome [45].

Metabolic Disorders

Gut bacteria play a key role in metabolism, influencing energy usage, nutrient absorption, and insulin function.

Obesity & Metabolic Syndrome:
Obesity is linked to less diverse gut bacteria and a higher ratio of Firmicutes to Bacteroidetes. Some bacteria extract more calories from food, promote low-level inflammation by releasing LPS (a bacterial component), and affect short-chain fatty acids (SCFAs) and amino acids that encourage fat storage and insulin issues [46,47].

Type 2 Diabetes (T2DM):
People with T2DM often have fewer butyrate-making microbes like Faecalibacterium prausnitzii and Roseburia, and more potentially harmful ones like Bacteroides and Ruminococcus gnavus. These changes can worsen insulin resistance, leaky gut, and inflammation [48,49].

Non-alcoholic Fatty Liver Disease (NAFLD)/Metabolic Liver Disease (MASLD):

• Early NAFLD: In this stage, gut bacteria may extract more calories and disrupt choline metabolism, leading to fat buildup in the liver [50].
• NASH & Fibrosis: As the disease progresses, the gut becomes “leakier,” letting bacterial molecules (like LPS) reach the liver and trigger inflammation and scarring. Typically, Ruminococcus gnavus and Enterobacteriaceae increase [51].

Autoimmune Diseases

Changes in gut microbes can affect immune cells and break the body’s self-tolerance, contributing to autoimmune conditions.

Rheumatoid Arthritis (RA):
RA patients often have more Prevotella copri and some Lactobacillus species, and fewer helpful Bacteroides and Bifidobacteria. This may increase gut permeability, letting bacterial products enter circulation and triggering autoimmune reactions that damage joints [52,53].

Multiple Sclerosis (MS):
MS patients commonly exhibit reduced Faecalibacterium prausnitzii and Butyricicoccus pullicaecorum, with increased Akkermansia muciniphila and Methanobrevibacter smithii. These changes may influence immune cells (like Th17), weaken the blood-brain barrier, and enhance neuroinflammation [54,55].

Type 1 Diabetes (T1DM):
In T1DM, early-life gut imbalances—fewer butyrate-producing bacteria and more inflammatory ones like Bacteroides and Clostridium—can cause leaky gut. This may let harmful substances enter the bloodstream and trigger the immune system to attack pancreatic cells [56].

Brain-Related and Mood Disorders (Gut–Brain Axis)

The gut and brain communicate closely, so bacterial imbalances can influence brain health.

Parkinson’s Disease (PD):
Gut changes often appear before PD symptoms: less Prevotellaceae and more Enterobacteriaceae. These shifts may lead to alpha-synuclein build-up in the gut, which could travel to the brain and contribute to nerve damage [57].

Autism Spectrum Disorder (ASD):
Many people with ASD have gut issues along with reduced bacterial diversity. They often have fewer Bifidobacteria and Prevotella, and more Clostridium. This imbalance may increase inflammation and disrupt the production of brain-related compounds, influencing behavior and brain development [58,59,60].

Depression & Anxiety:
Those with mood disorders often have less diverse gut bacteria and fewer SCFA producers like Faecalibacterium and Coprococcus, plus more pro-inflammatory species. This can affect neurotransmitters like serotonin and GABA, fuel brain inflammation, and deregulate stress systems like the HPA axis [61,62].

Cancer

Gut bacteria can influence cancer development, growth, and how patients respond to treatments.

Colorectal Cancer:
CRC is linked to more Fusobacterium nucleatum, Porphyromonas, and Enterococcus faecalis, and fewer butyrate producers. These harmful microbes can provoke inflammation, cause DNA damage, activate cancer-related pathways, and help tumors grow and spread [63,64].

Liver Cancer:
Especially in NAFLD/NASH, a leaky gut allows bacteria and their products to reach the liver, promoting chronic inflammation, oxidative damage, scarring, and possible progression to cancer [65,66].

Cancer Immunotherapy Response:
The gut microbiome affects how well patients respond to checkpoint inhibitors (like PD-1‑1/PD‑PD-L1 drugs). Certain bacteria—such as Akkermansia muciniphila, Bifidobacterium longum, and some Ruminococcaceae—are linked to better outcomes, while an unhealthy microbiome can reduce treatment effectiveness [67,68].

Challenges:

Defining a "Healthy" Microbiome and Individual Differences:
One major challenge is figuring out what exactly a "healthy" gut microbiome looks like. People have very different gut bacteria due to their genes, diet, lifestyle, age, and where they live. Because of these personal differences, it's hard to create one standard for what’s normal or unhealthy. This means treatments often need to be tailored to each person [69,70,71].

Understanding Cause vs. Correlation:
Many studies have shown links between imbalanced gut bacteria and diseases, but proving that gut changes directly cause illness is tricky. To truly understand this, we need long-term studies, detailed lab research, and reliable animal models that can show whether changes in the microbiome are a cause, a result, or just a side effect of disease [72].

Lack of Standard Methods and Reproducibility Issues:
Results from microbiome studies can vary a lot because of differences in how samples are collected, stored, and tested. Methods like DNA extraction, sequencing techniques, and data analysis are not always consistent, making it hard to compare results across different studies. Standardized procedures are needed for reliable and reproducible outcomes [73,74].

Future Directions in Gut Microbiome Research and Therapy

Personalized Microbiome Treatments:
In the coming years, treatments that target the gut microbiome will likely become much more personalized. This means using detailed biological data from each person—like their genes, gut bacteria, metabolism, and immune system—to create tailored diets, choose the right probiotics, or design custom mixes of helpful microbes to support health or treat illness [75].

Advanced Probiotics and Engineered Microbes:

• Custom Microbial Mixes:
  Instead of using just one type of probiotic, researchers are now working on combinations of carefully chosen bacterial strains that work together to give stronger and more reliable health benefits. These blends aim to mimic the natural balance found in healthy guts [76].
• Engineered Microbes for Therapy:
  Thanks to gene-editing tools like CRISPR, scientists can now modify gut bacteria to produce helpful substances—such as enzymes or anti-inflammatory agents—directly in the gut. These specially designed microbes offer targeted treatments, but challenges remain in making sure they work safely and reach the right place in the body [77].

Exploring Viruses and Fungi in the Gut:
So far, most studies have focused on gut bacteria, but researchers are beginning to pay more attention to the gut virome (viruses, especially those that infect bacteria) and fungi. One promising area is phage therapy, which uses specific viruses to kill harmful bacteria, especially when antibiotics no longer work [78].

Using Microbial Byproducts as Medicines:
Scientists are also looking into using purified substances made by gut microbes—called postbiotics—instead of using the microbes themselves. These include things like short-chain fatty acids and modified bile acids, which can offer health benefits without needing to manage live bacteria [79].

AI and Data Science in Microbiome Research:
The huge amount of data generated in microbiome studies is hard to analyze. Artificial intelligence and machine learning are becoming vital tools to find hidden patterns, predict health risks, personalize treatments, and discover new microbial markers or therapy targets [80,81].

Better Ways to Deliver Treatments:
New delivery methods are being developed to make sure probiotics, engineered microbes, or their beneficial products survive the journey through the digestive system and reach the right part of the gut. These include smart capsules, protective coatings, and even modified viruses to deliver the treatment [82].

CONCLUSION:

Unquestionably a fundamental component of human health, the complex and dynamic gut microbiota has a significant impact on a wide range of physiological functions, from metabolism and immunity to neurological function. A wide range of disorders, including cardiovascular, metabolic, autoimmune, neurological, and neoplastic conditions, are now known to be significantly influenced by its dysregulation. Despite the fact that current microbiome-based therapies, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), present promising avenues for intervention, obstacles like inter-individual variability, a lack of mechanistic understanding, and standardization issues hinder their widespread and consistent clinical application. It is imperative that future research be driven by cutting-edge technology such as engineered microbes, AI-driven data analysis, personalized microbial treatments, and a more thorough investigation of the gut virome and mycobiome. These developments have the potential to fully unleash the medicinal potential of Understanding the gut microbiota, opening the door to more focused, efficient, and customized treatments that target the underlying microbial imbalances causing human illness and promote overall health.

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71.  Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018). Role of the gut microbiota in nutrition and health. BMJ, 361, k2179. (This reference also covers the complexity of defining a healthy microbiome and the need for personalized approaches.)

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