Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases

Table 1 Gut bacteria and their mechanisms of involvement in various disorders

Sl No.	Disease	Mechanism of involvement	Key bacteria implicated	Ref.
1	Alzheimer’s disease	Gut microbiota influences neuroinflammation and cognitive function; modulation of SCFA production affects brain health	Lactobacillus spp., Bifidobacterium spp.	[32]
2	Anxiety and depression	Dysbiosis, inflammation, cytokine release, HPA axis dysregulation	Bifidobacterium, Lactobacillus	[33]
3	Anxiety disorders	Gut microbiota-induced alterations in neurotransmitter levels and stress response pathways; modulation of vagus nerve activity	Campylobacter jejuni, Lactobacillus rhamnosus	[34]
4	Autism spectrum disorders	Interaction between Candida albicans and bacterial metabolites	Candida albicans	[35]
		Changes in gut microbiota affecting neurodevelopment and behavior; disruption in SCFA metabolism affecting microglial function	Bacteroides spp., Firmicutes spp.	[36]
5	Cognitive impairment	Gut microbiota affecting cognitive control and executive function networks such as the FPN and DMN	Bacteroides, Prevotella, Ruminococcus	[37]
6	Depression	Dysbiosis leading to increased intestinal permeability and systemic inflammation; alterations in serotonin and other neurotransmitter levels	Lactobacillus spp., Bifidobacterium spp.	[38]
		Chronic low-grade inflammation and altered neuroplasticity; influence on HPA axis and neurotransmitter metabolism	Lactobacillus spp., Bifidobacterium spp.	[39]
7	Emotional and interoceptive awareness	Gut microbiota composition associated with brain areas involved in emotional and visceral interoception	Roseburia, Bacteroides	[40]
8	Irritable bowel disease	Disruption in the balance of gut microbiota leads to chronic inflammation and dysbiosis affecting mood and stress responses	Faecalibacterium prausnitzii, Bacteroides spp.	[41]
9	Irritable bowel syndrome	Gut microbiota-induced inflammation and dysregulation of the enteric nervous system; alterations in gut motility and visceral hypersensitivity	Bifidobacterium spp., Lactobacillus spp.	[42]
10	Mood disorders	Alterations in gut-brain communication affecting mood-related brain networks	Bifidobacterium, Collinsella	[43]
11	Neurological disorders	Influence on neuroinflammation, gut-brain axis communication	Lactobacillus, Bacteroides	[44]

SCFA: Short-chain fatty acid; HPA: Hypothalamic-pituitary-adrenal; FPN: Frontoparietal network; DMN: Default mode network.

Table 2 Microbiota-associated mechanisms in autoimmune and inflammatory diseases: Insights and implications

Sl No.	Disease	Mechanism of involvement	Key bacteria implicated	Ref.
1	Allergies	Modulation of immune responses, allergic inflammation	Clostridium, Bifidobacterium	[49]
2	Autoimmune diseases	Dysregulated immune responses, inflammation	Prevotella, Bacteroides	[50]
3	Cardiovascular diseases	Production of trimethylamine N-oxide, systemic inflammation	Prevotella, Firmicutes	[51]
4	Inflammatory bowel disease	Dysregulated immune responses against microbiota lead to chronic inflammation in the GI tract. Reduced anti-inflammatory microbes and increased potentially inflammatory microbes. SCFAs and dietary factors influence disease progression	Decreased Bacteroidetes, Lachnospiraceae, Faecalibacterium prausnitzii. Increased Proteobacteria, Ruminococcus gnavus. Key producers: Faecalibacterium prausnitzii, Roseburia hominis. Pathogens: Vancomycin-resistant Enterococcus	[52]
		Associated with reduced anti-inflammatory response. Increased pro-inflammatory activity	Reduced abundance of Faecalibacterium prausnitzii. Overgrowth of Escherichia coli	[53]
5	Liver diseases	Regulation of bile acid metabolism, inflammation	Enterococcus, Ruminococcus	[54]
6	Multiple sclerosis	Microbiota interaction: Dysbiosis with increased Euryarchaeota and Verrucomicrobia. Microbial impact: Modulation of T cell responses and inflammation in the central nervous system. Protective effects: Certain bacteria and metabolites have protective effects against disease	Increased: Methanobrevibacter smithii, Akkermansia muciniphila. Decreased: Clostridia clusters XIVa and IV, Bacteroidetes. Protective: Lactobacillus reuteri, Lactobacillus murinus	[55]
		Akkermansia muciniphila and Acinetobacter calcoaceticus induce pro-inflammatory responses. Parabacteroides distasonis stimulates anti-inflammatory Tregs	Decreased abundance of Lachnospiraceae and Faecalibacterium. Increased abundance of Akkermansia spp.	[56]
7	Respiratory infections	Modulation of respiratory immune responses, inflammation	Streptococcus, Haemophilus	[57]
8	Rheumatoid arthritis	Dysbiosis contributes to systemic inflammation and joint symptoms; gut barrier dysfunction affecting overall immune response	Prevotella spp., Fusobacterium spp.	[58]
		Microbiota interaction: Oral and intestinal dysbiosis linked to disease severity and immune responses. Microbiota influence: Microbial DNA and peptidoglycan-polysaccharide complexes found in joints. Microbial-induced immunity: Certain bacteria drive inflammation through immune cell activation	Oral dysbiosis: Porphyromonas gingivalis, Lactobacillus salivarius. Intestinal dysbiosis: Increased Gram-positive bacteria, Prevotella copri. Exacerbation: Prevotella copri, Segmented filamentous bacteria	[59]
		Pro-inflammatory molecule production. Autoreactive immune cell activation. Linked to RA susceptibility with specific HLA-DRB1 alleles	Overgrowth of Prevotella spp., reduction in Bacteroides, Bifidobacterium, butyrate-producing bacteria, and high abundance of Ruminococcus gnavus	[60]
9	Systemic lupus erythematosus	Microbiota interaction: Dysbiosis in oral and gut microbiota contributes to disease through molecular mimicry and bacterial antigen recognition. Metabolic factors: Bacterial metabolites impact disease severity	Increased: Lactobacillaceae, Ruminococcus gnavus. Decreased: Bifidobacteria, Clostridiales. Specific antigens: Propionibacterium propionicum, Bacteroides thetaiotaomicron	[61]

SCFA: Short-chain fatty acid; GI: Gastrointestinal; Treg: Regulatory T cell.

Table 3 Overview of gut microbiota’s role in diabetes and mechanistic insights

Sl No.	Disease/drug target	Mechanism of involvement	Key bacteria or drug implicated	Ref.
1	GLP-1 receptor agonists	Mimic the incretin GLP-1, enhancing insulin secretion, slowing gastric emptying, and altering gut microbiota composition	Decreased: Allobaculum, Turicibacter, Anaerostipes, Blautia, Lactobacillus, Butyricimonas, Desulfovibrio, Clostridiales, Bacteroidales. Increases: Akkermansia muciniphila	[67]
2	Insulin	Improves glycemic control by increasing glucose uptake into cells. Minimal direct impact on gut microbiota	Minimal direct effect on humans. In rats, it increased Norank_f_Bacteroidales_S24-7 and decreased Lactobacillus and Peptostreptococcaceae, suggesting possible effects on gut bacteria in animal models. Effect on T2DM: Influences microbiota dysbiosis in T2DM patients, potentially regulating inflammation and gut health	[68]
3	Metabolic syndrome	Increased intestinal permeability leading to systemic inflammation; effects on metabolic pathways and mood	Increased: Lactobacillus spp., Bacteroides spp.	[69]
4	Obesity	Gut microbiota affecting metabolic processes and inflammatory responses; alterations in appetite regulation and mood	Increased: Firmicutes spp., decreased: Bacteroidetes spp.	[70]
		Metabolic dysregulation, energy extraction from diet	Increased: Bacteroides, Firmicutes	[71]
5	SGLT2 inhibitors	Inhibit SGLT2 in the proximal tubule, preventing glucose reabsorption and promoting glucose excretion in urine. Limited impact on gut microbiota reported	Dapagliflozin is used as drug. Ruminococcaceae, Proteobacteria (Desulfovibrionaceae); Sotagliflozin changes in Firmicutes/Bacteroidetes ratio with high-sucrose diet	[72]
6	Type 1 diabetes	Altered microbiota composition influencing the immune system and glucose metabolism	Decrease: Prevotella, Akkermansia. Increase: Actinobacteria, Bacteroidetes, Proteobacteria, Lactobacillus, Lactococcus, Bifidobacterium, Streptococcus	[73]
		Increased abundance of certain bacteria linked to inflammation and immune responses. Decreased abundance of beneficial bacteria	Increase: Clostridium, Bacteroides, Veillonella. Decrease: Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale, Prevotella	[74]
		Insulin resistance, inflammation	Decreased: Akkermansia muciniphila, Bifidobacterium	[75]
		Microbial composition influences immune responses and disease onset	Decreased: Bifidobacteria, Lachnospiracea	[76]
7	Type 2 diabetes mellitus	Changes in bile acid metabolism affecting glucose metabolism	Involvement of Clostridium, Eubacterium, Bacteroides, Lactobacillus, Bifidobacterium	[77]
		Correlation between gut microbiota composition and inflammatory markers influencing diabetes progression	Increased: Bacteroidetes, Proteobacteria. Decreased: Roseburia, Firmicutes, Clostridiaceae	[78]
		Imbalance in microbiota affecting glucose metabolism and insulin sensitivity	Decrease: Firmicutes. Increase: Bacteroidetes, Proteobacteria, Lactobacillus, Faecalibacterium prausnitzii, Blautia, Serratia	[79]
		Increased abundance of certain bacteria linked to metabolic dysfunction and inflammation	Increase: Faecalibacterium prausnitzii, Blautia. Decrease: Verrucomicrobia phylum	[80]
		Influence of SCFA production on insulin sensitivity and glucose metabolism	Increase: Bacteroides, Ruminococcus, Akkermansia muciniphila. Decrease: Roseburia, Clostridium	[81]
		Inhibit the enzyme DPP-4, which prolongs the action of incretins (e.g., GLP-1), enhancing insulin secretion and reducing glucose levels. Effects on microbiota include changes in diversity and composition	Sitagliptin and Blautia used as drug. Blautia increases, while changes in Roseburia, Clostridium, Bacteroides, Erysipelotrichaceae, and Firmicutes are variable and require more research	[82]

T2DM: Type 2 diabetes mellitus; SCFA: Short-chain fatty acid; GLP-1: Glucagon-like peptide-1; DPP-4: Dipeptidyl peptidase-4; SGLT2: Sodium-glucose cotransporter 2.

Table 4 Gut microbiota’s role in cancer progression: mechanistic insights and key bacterial implications

Sl No.	Disease	Mechanism of involvement	Key bacteria implicated	Ref.
1	Breast cancer	Modulation of systemic inflammation, hormone metabolism	Lactobacillus, Prevotella	[88]
		Gut microbiota impacts hormone levels and immune responses. Microbiota may modulate estrogen levels and immune cell infiltration in breast tissue, affecting cancer risk and progression	Clostridium, Bifidobacterium	[89]
2	Colorectal cancer	Chronic inflammation, carcinogen metabolism	Fusobacterium nucleatum, Escherichia coli	[90]
		Gut microbiota influences chemotherapy efficacy. Microbial dysbiosis can affect drug metabolism and immune responses, altering treatment outcomes	Fusobacterium nucleatum, Bacteroides	[91]
3	Esophageal cancer	Dysbiosis in esophageal microbiome, inflammatory pathways	Prevotella, Fusobacterium	[92]
		Dysbiosis in esophageal microbiota is associated with cancer. Microbial-induced inflammation and changes in the esophageal microenvironment can contribute to cancer development	Prevotella, Streptococcus	[93]
4	Gastric cancer	Disruption of gastric mucosa, inflammation	Helicobacter pylori	[94]
		Helicobacter pylori is a major risk factor for gastric cancer. Chronic infection with Helicobacter pylori causes inflammation and genetic alterations leading to cancer	Helicobacter pylori	[95]
5	Liver cancer	Modulation of liver inflammation, bile acid metabolism	Enterococcus, Bacteroides	[96]
		Gut microbiota can contribute to liver cancer development. Microbiota produced metabolites and inflammation can promote liver cancer progression	Enterococcus faecalis, Bacteroides	[97]
6	Lung cancer	Impact on lung microbiome, immune response modulation	Streptococcus, Bacteroides	[98]
		Oral and gut microbiota are linked to lung cancer risk. Inhaled microbiota or systemic effects from gut microbiota can influence lung inflammation and carcinogenesis	Streptococcus, Veillonella	[99]
7	Melanoma	Systemic immune modulation, tumor microenvironment	Bifidobacterium, Lactobacillus	[100]
8	Ovarian cancer	Role in local inflammation, metabolic influences	Ruminococcus, Clostridium	[101]
9	Pancreatic cancer	Alteration of pancreatic microenvironment, immune modulation	Akkermansia muciniphila, Bifidobacterium	[102]
		Microbiota composition affects pancreatic cancer development. Specific bacteria may modulate inflammation and immune responses in the pancreas	Porphyromonas gingivalis, Fusobacterium nucleatum	[103]
10	Prostate cancer	Influence on androgen metabolism, immune modulation	Clostridium, Firmicutes	[104]

Table 5 Clinical implications and therapeutic strategies targeting the gut microbiota

Sl No.	Therapeutic strategy	Description	Clinical application	Ref.
1	Antibiotics	Targeted use to treat dysbiosis or specific bacterial infections affecting gut health	Used in severe cases of gut dysbiosis	[118]
2	Biofilm disruptors	Compounds that disrupt bacterial biofilms in the gut, enhancing susceptibility to treatment	Investigated for their potential in chronic infection treatments	[119]
3	Butyrate supplementation	Providing the short-chain fatty acid butyrate to support gut barrier function and reduce inflammation	Studied for efficacy in treating ulcerative colitis	[120]
4	Colonization resistance	Strategies to enhance the gut’s ability to resist colonization by harmful bacteria	Investigated in preventing infections in hospitalized patients	[121]
5	Dietary modifications	Including high-fiber diets, Mediterranean diet, and low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet to support gut microbiota	Management of symptoms in irritable bowel syndrome	[122]
6	Enteral nutrition	Providing nutrients directly into the gastrointestinal tract to support gut health	Used in patients unable to tolerate oral intake	[123]
7	Fecal microbiota transplantation	Transfer of fecal microbiota from a healthy donor to restore microbial diversity in the recipient	Effective treatment for recurrent Clostridium difficile infection	[124]
8	Gut microbiota modulators	Pharmaceuticals that target specific pathways or microbes within the gut	Studied for their potential in precision medicine approaches	[125]
9	Microbial consortia therapy	Using multiple species of bacteria to restore healthy microbial balance	Investigated in treating recurrent bacterial infections	[126]
10	Microbial ecosystem therapeutics	Engineered microbial communities designed to restore or enhance gut health	Investigated for potential in treating inflammatory diseases	[127]
11	Microbiota-targeted dietary interventions	Specific diets aimed at altering the composition and function of gut microbes	Used in managing metabolic syndrome and obesity	[128]
12	Phage therapy	Using bacteriophages to selectively target harmful bacteria in the gut microbiota	Potential alternative to antibiotics in treating infections	[129]
13	Postbiotics	Metabolites produced by probiotic bacteria have beneficial effects on host health	Investigated for potential in treating metabolic disorders	[130]
14	Prebiotics	Non-digestible fibers that promote the growth of beneficial bacteria in the gut	Improve gut health and reduce inflammation in IBD patients	[131]
15	Probiotics	Live microorganisms that confer health benefits by colonizing the gut and influencing microbial balance	Used to restore gut microbiota after antibiotic therapy	[132]
16	Protein therapeutics	Engineered proteins designed to modulate microbial activity in the gut	Investigated for their role in targeted microbiota treatments	[133]
17	Proton pump inhibitors	Medications that alter gastric acidity and impact gut microbiota composition	Used to manage symptoms of gastroesophageal reflux disease	[134]
18	Stool substitutes	Synthetic or cultured microbial communities for fecal microbiota transplantation when donor stool is unavailable or impractical	Investigated as a potential treatment for chronic infections	[135]
19	Symbiotics	Combination of probiotics and prebiotics to enhance gut health	Used in enhancing gut health and immune function	[136]
			Studied for efficacy in treating diarrhea in children	[137]

IBD: Inflammatory bowel disease.

Table 6 Current research gaps in understanding the gut microbiota’s role in disease and cancer

Sl No.	Aspect	Description	Ref.
1	Crosstalk with immune system	Microbiota interact with the immune system. Research should focus on how these interactions influence autoimmune diseases, allergies, and cancer	[160]
2	Impact of antibiotics and therapeutics	Antibiotics and medications alter microbiota. Understanding these effects is important for assessing long-term health consequences	[161]
3	Interaction with host genetics	Host genetics influence microbiota. Understanding these interactions is key to linking genetic predispositions with microbiota and disease risk	[162]
4	Mechanistic understanding	While correlations between microbiota and diseases exist, the mechanisms remain unclear. Future studies should explore specific microbial influences on disease	[163]
5	Microbial metabolites and signaling	Microbial metabolites affect host physiology. Identifying these metabolites and their role in disease modulation is crucial	[164]
6	Microbiota and cancer immunotherapy	Gut microbiota impact cancer immunotherapy efficacy, but mechanisms are poorly understood. Identifying beneficial microbial profiles is necessary	[165]
7	Microbiota in early life and development	Early microbiota establishment affects long-term health. Research should examine its impact on immune and metabolic development	[166]
8	Microbiota in extraintestinal diseases	Gut microbiota may influence non-gut diseases like cardiovascular and neurological disorders. Research is needed to explore these associations	[167]
9	Need for longitudinal studies	Most studies are cross-sectional; longitudinal research is needed to track microbiota changes over time in relation to disease	[168]
10	Role of diet and lifestyle	Diet and lifestyle significantly influence microbiota. Research should focus on how these factors affect microbiota and disease risk	[169]
11	Gender differences in microbiota	Gender-specific microbiota differences influence disease outcomes. Research should explore how these variations impact health between males and females	[170]
12	Variability in microbiota composition	Challenges arise due to factors like diet, genetics, and lifestyle. Research lacks comprehensive large-scale studies on these interactions	[171]