Table of Content

Gut Microbiome Dysbiosis Across Disease States: A Contemporary Review......................................3

Abstract..........................................................................................................................................3
1 Introduction.................................................................................................................................4
2 Gut Dysbiosis in Metabolic Disorders............................................................................................5
2.1 Type 2 Diabetes Mellitus (T2DM)..........................................................................................5
2.1.1 Microbial Diversity and Composition:............................................................................5
2.1.2 Mechanistic Insights:.....................................................................................................6
2.1.3 Therapeutic Perspectives...............................................................................................6
2.2 Obesity.................................................................................................................................6
2.2.1 Changed Formicates-to-Bacteroidetes Ratio:.................................................................7
2.2.2 Inflammatory Pathways and Energy Harvest:.................................................................7
2.2.3 Intervention Strategies:.................................................................................................8
2.3 Gut Dysbiosis in Neurodegenerative Disorders......................................................................8
2.3.1 Alzheimer's Disease (AD):..............................................................................................8
2.3.2 Parkinson's Disease (PD):...............................................................................................8
2.4 Gut Dysbiosis in Cardiovascular Diseases...............................................................................9
2.4.1 Atherosclerosis:.............................................................................................................9
2.4.2 Atrial Fibrillation (AF):..................................................................................................10
2.5 Gut Dysbiosis in Cancer.......................................................................................................10
2.5.1 Colorectal carcinoma (CRC):.........................................................................................10
2.5.2 Pancreatic and Other Cancers:.....................................................................................10
2.6 Gut Dysbiosis in Autoimmune and Inflammatory Diseases..................................................10
2.6.1 Inflammatory Bowel Disease (IBD):..............................................................................10
2.6.2 Rheumatoid Arthritis (RA):...........................................................................................11
2.6.3 Aopic Dermatitis (AD):.................................................................................................11
3 Methodology and Literature Selection........................................................................................15
3.1 Technological Advances in Microbiome Profiling.................................................................19
4 Conclusion:................................................................................................................................20
5 References.................................................................................................................................22
Gut Microbiome Dysbiosis Across Disease States: A Contemporary Review

Abstract

The gut microbiome is an active, intricate ecosystem that supports host homeostasis. Dysbiosis

interruptions of microbial composition and function have arisen as a main driver of

pathophysiology in most diseases. While high-throughput sequencing technologies have

improved our knowledge profoundly, they are not able to provide a concrete definition of a

"healthy" microbial community. Hence, the detection of compositional change mechanisms

during disease remains a main focus in microbiome studies. The review consolidates advances

(2023–2025) in microbiome alteration in major disease classes, i.e., metabolic disease,

neurodegeneration, cardiovascular disease, autoimmune diseases, and malignancies. We

highlight mechanistic linkages such as immune modulation, microbial metabolites, and host-

microbe interaction, and outline emerging microbiome-directed therapy. Current controversy

about causality versus correlation, and personalization of microbiome treatment, determines key

areas of future research. Enhanced knowledge about disease-specific dysbiosis might determine

new diagnostic and therapeutic methods.

1 Introduction

The human gut microbiome, an active community of trillions of microbes consisting of bacteria,
viruses, fungi, and archaea, is central to the regulation of digestion, immunity, metabolism, and
host defense against pathogens (Gomaa, 2020). Dysbiosis, or disruptions in the homeostatic
community of the gut microbiome, has been associated with the aetiology and pathogenesis of
numerous diseases (Dixit et al., 2021). High-throughput sequencing technologies (e.g., 16S
rRNA and metagenomics) have identified correlations between microbial dysbiosis and disease
and have been utilized to confirm the heterogeneity of microbiota according to diet, geography,
and genetics. This heterogeneity complicates the definition of a universally "healthy"
microbiome (Brandão et al., 2020; Mongraw-Chaffin et al., 2018).

Dysbiosis is the cause of a multitude of diseases and conditions, which include obesity, type 2
diabetes, rheumatoid arthritis, inflammatory bowel disease (IBD), Alzheimer's and Parkinson's
disease, cardiovascular disease, and cancer (e.g., colorectal and pancreatic cancer)
(Doroszkiewicz et al., 2024). Some of the common dysbiosis characteristics involve reduced
microbial diversity, enhanced proliferation of pro-inflammatory species (e.g.,
Enterobacteriaceae, Clostridium spp.), and loss of barrier microorganisms like
Faecalibacterium prausnitzii and Akkermansia muciniphila (Di Stefano et al., 2023).

Mechanistically, dysbiosis may initiate disease through impaired gut barrier function (Stolfi et
al., 2022), reduced production of beneficial metabolites like SCFAs (Belizário et al., 2018),
increased gut permeability (Nagpal et al., 2018), dissemination of microbial toxin within the
body like LPS, and chronic inflammation (Guerville & Boudry, 2016). In neurological disease,
gut-brain axis enables communication between brain and microbes through immune, neural, and
metabolic pathways (Suganya & Koo, 2020).

Despite the existence of promising therapies like probiotics, prebiotics, symbiotic, and fecal
microbiota transplantation (FMT), difficulties are encountered with unstable outcomes and
concerns as to whether dysbiosis causes disease or disease causes dysbiosis (Karimi et al., 2024).
In an effort to address these gaps, more recent research requires mechanism-based, routine
investigations. Here, this review integrates new evidence to assist in making sense of microbial
alterations, disease processes, and therapeutic interventions to gut dysbiosis.
2 Gut Dysbiosis in Metabolic Disorders

Metabolic disturbances, particularly obesity and T2DM, form a global public health problem that

has far-reaching social as well as economic significance (Magliano & Boyko, 2022; Ruze et al.,

2023). Accumulated evidence has underscored the engagement of dysbiosis of gut microbiota

increasingly in the diseases' pathogenesis (Bielka et al., 2022). Changes in microbial architecture

as well as functionality have been identified to alter the host's metabolism via a continuum of

interconnected pathways such as long-term inflammation, altered energy production, and loss of

gut barrier function (Lindsay et al., 2020).

2.1 Type 2 Diabetes Mellitus (T2DM)

Research in the past two years has further delineated the relationship between gut dysbiosis and

T2DM. A synbiotic containing Faecalibacterium prausnitzii decreased HbA1c by 0.8% at 12

weeks (Kallassy et al., 2023). The following are points to note:

2.1.1 Microbial Diversity and Composition:

Lower microbial richness was noted in T2DM patients in recent studies (Chen et al., 2021).

Some of the studies have indicated a spectacular reduction in the relative abundance of the

health-promoting bacteria such as Faecalibacterium prausnitzii and Bifidobacterium spp.

(Lordan et al., 2020) and an increase in opportunistic pathogens which are pro-inflammatory in

nature. This compositional shift destabilizes the integrity of the gut barrier and supports systemic

inflammation (Dey & Ray Chaudhuri, 2023).

2.1.2 Mechanistic Insights:

Microbial-derived products, including the short-chain fatty acids (SCFAs) like butyrate, are

critical in regulation of insulin sensitivity and inflammatory function (Campos-Perez &

Martinez-Lopez, 2021; Guo et al., 2022). Dysbiosis in T2DM was linked to reduction in SCFA

production and as such is contributing to insulin resistance and metabolic derangement

(Salamone et al., 2021). In addition, elevated intestinal permeability ("leaky gut") associated

with T2DM facilitates passage of lipopolysaccharides (LPS) from the gut luminal contents across

the epithelia into the systemic circulation, promoting further induction in a state of chronic low-

grade inflammation a reported factor in pathophysiology in T2DM (Di Vincenzo et al., 2024).

2.1.3 Therapeutic Perspectives

Interventions like probiotics, prebiotics, and dietary modification are being researched actively to

restore microbial balance and suppress inflammatory responses (Bilal et al., 2022). For instance,

supplementation with butyrate-producing bacteria or symbiotic formulations has shown

encouraging results in enhancing glycemic control (Perraudeau et al., 2020).

2.2 Obesity

Obesity, a major risk factor for cardiovascular disease and metabolic syndrome, has also been

strongly associated with changes in the gut microbiota (Wang et al., 2020). The study points out

several salient points:

2.2.1 Changed Formicates-to-Bacteroidetes Ratio:

Arguably the most reliable finding in obesity is an elevated Firmicutes/Bacteroidetes ratio

compared with lean individuals (Magne et al., 2020). The ratio is suggested to enhance the

efficiency of caloric harvest from the diet and result in over-weight gain (Amabebe et al., 2020).

2.2.2 Inflammatory Pathways and Energy Harvest:

The dysbiotic microbial community in obesity is frequently dominated by an excess of

inflammatory bacterial species. These microorganisms have the potential to induce systemic

inflammation through the release of endotoxins and other pro-inflammatory mediators (Cristofori

et al., 2021; Douglas et al., 2020). Moreover, dysregulated bile acid metabolism, regulated by the

gut microbial community, can influence energy homeostasis and fat accumulation (Xie et al.,

2021).

Mech

anisms of the

gut

microbiota leading to inflammatory diseases (Zhao et al., 2023).

2.2.3 Intervention Strategies:

Prebiotic fiber in the diet has been observed to shape the gut microbial community towards a

healthier composition (Cantu-Jungles & Hamaker, 2020). Likewise, probiotic therapy for

targeted restoration of health-promoting taxa is being researched as an adjunct therapy in obesity

treatment (Cho et al., 2025). New research also examines how alterations in dietary fat

composition may interact with microbial population structure to worsen or improve obesity.

2.3 Gut Dysbiosis in Neurodegenerative Disorders

2.3.1 Alzheimer's Disease (AD):

AD patients have lower microbial diversity and dysbalanced abundances of certain microbial

taxa (Verhaar et al., 2022). In particular, decreases in SCFA-producing bacteria are typically

observed, which have the potential to destabilize the anti-inflammatory context required for

neural well-being (Ventura et al., 2024). Dysbalanced gut microbial metabolites can also cause

amyloid-beta deposition and neuro inflammation, suggesting that dysbiosis is an etiological

contributor to the development of disease (Liu et al., 2020).

2.3.2 Parkinson's Disease (PD):

Gut dysbiosis can precede traditional motor PD symptoms (Wang et al., 2021). Altered microbial

profiles and disrupted metabolic signatures e.g., reduced levels of anti-inflammatory SCFAs can

trigger systemic and neuro inflammatory cascades involved in dopaminergic neuron death

(Kalyanaraman et al., 2024). Even therapeutic drugs that correct such imbalances are being
actively investigated, with preliminary studies indicating the potential of probiotics in reducing

PD symptoms (Zhu et al., 2022).

Mechanisms of the Gut Microbiota-Gut-Brain Axis in the Pathogenesis of

Neurodegenerative Diseases (Zhao et al., 2023).

2.4 Gut Dysbiosis in Cardiovascular Diseases

2.4.1 Atherosclerosis:

Dysbiosis can foster atherogenesis through lipometabolic changes and enhanced systemic
inflammation (Anto & Blesso, 2022). Some metabolites generated in the gut e.g., trimethylamine
N-oxide (TMAO) have been shown to drive plaque progression (Zhu et al., 2020). Recent
evidence suggests that changes in microbial composition can influence concentrations TMAO
and affect cardiovascular risk (Heianza et al., 2020).

2.4.2 Atrial Fibrillation (AF):

Dysbiotic signatures of overabundance of pro-inflammatory taxa are associated with atrial

remodeling and electrophysiological alterations (Gawałko et al., 2022). The interaction between
microbial-derived inflammatory mediators with cardiac tissue implicates a new, but complicated,
role of gut dysbiosis in AF pathophysiology (Li et al., 2023).

2.5 Gut Dysbiosis in Cancer

2.5.1 Colorectal carcinoma (CRC):

A large body of recent studies has identified specific microbial signatures as being associated
with the colorectal carcinogenesis process. For example, a rise in bacteria such as Fusobacterium
nucleatum and a decrease in beneficial commensals are recurrent findings in CRC patients
(Wang & Fang, 2023). Such shifts in the microbial composition may likely contribute to a pro-
inflammatory microenvironment, increase genomic instability, and affect host immune
responses, hence all facilitating tumorigenesis (Anuja et al., 2017).

2.5.2 Pancreatic and Other Cancers:

Dysbiosis also impacts pancreatic and other cancers. Alterations in microbial community may
have the potential to influence bile acid metabolism and systemic inflammation, both of which
are involved in cancer pathogenesis (Collins et al., 2023).

While the relationship between gut dysbiosis and cancer is complex, the inclusion of microbial
analysis in oncology diagnostics has the potential to lead to targeted treatments.

2.6 Gut Dysbiosis in Autoimmune and Inflammatory Diseases

2.6.1 Inflammatory Bowel Disease (IBD):

Dysbiosis in IBD is also associated with loss of microbial diversity and decreased protective
commensal flora like Faecalibacterium prausnitzii (He et al., 2021). The imbalance is
hypothesized to worsen intestinal inflammation through compromised barrier function and
disrupted immune activation. New trials using microbiome-directed therapies (e.g., FMT,
targeted probiotics) are forthcoming promising in destabilizing the gut microbiota and mitigating
the severity of the disease (Sorbara & Pamer, 2022).

2.6.2 Rheumatoid Arthritis (RA):

RA patients usually carry some changes in gut microbiota, such as an increase in pro-
inflammatory bacteria. These changes can influence systemic immune responses and enhance the
inflammation in the joints (Lin et al., 2023). Early evidence suggests that treatments aimed at the
gut microbiota are potentially capable of managing disease activity and improving clinical
responses in RA (Scher et al., 2020).

2.6.3 Aopic Dermatitis (AD):

Although traditionally viewed as a dermatological disorder, recent findings point towards early-
life gut dysbiosis predisposing to atopic dermatitis by influencing immune system development.
Decreased colonization with beneficial bacteria in infancy is linked with increased risk of
allergic sensitization and chronic inflammatory skin disease (Renz & Skevaki, 2021).

Table 1: Comparative Overview of Gut Microbiome Dysbiosis in Disease States

Mechanistic Therapeutic Reference

Disease State Dysbiotic Features
Implications Approaches

Metabolic Type 2 Diabetes Mellitus • Impaired gut • Dietary

Disorders (T2DM): barrier function modifications

• Reduced overall microbial leading to (e.g., high- (Que et al.,

diversity increased fiber diets) 2021)

• Depletion of beneficial taxa intestinal • Probiotics,

(e.g., Faecalibacterium permeability prebiotics, and (Liaqat et

 Mechanistic Therapeutic Reference
Disease State Dysbiotic Features
Implications Approaches

(“leaky gut”) al., 2021)

• Reduced SCFA

production (Stojanov et

prausnitzii, Bifidobacterium contributing to al., 2020)

symbiotic
spp.) systemic
• Personalized
Obesity: inflammation and
nutritional
• Increased Firmicutes-to- insulin resistance
interventions
Bacteroidetes ratio • Enhanced energy

extraction from

the diet (in

obesity)

Neurodegenerative Alzheimer’s Disease: • Disruption of the • Probiotic and

Disorders • Lower diversity, decreased gut-brain axis dietary

SCFA producers • Promotion of interventions (Marizzoni,

Parkinson’s Disease: neuro • Strategies Cattaneo, et

• Altered microbial profiles inflammation and targeting the al., 2020)

with reduced anti- deposition of gut-brain axis

inflammatory metabolites neurotoxic (Augustin et

proteins al., 2023)

• Altered

neurotransmitter
 Mechanistic Therapeutic Reference
Disease State Dysbiotic Features
Implications Approaches

metabolism

Atherosclerosis:
• Modulation of
• Enrichment of pro-
lipid metabolism • Microbiome-
inflammatory taxa leading to (Mahdavi-
and promotion of targeted
altered production of microbial Roshan et
plaque formation therapies
Cardiovascular metabolites (e.g., TMAO) al., 2022)
(atherosclerosis) • Dietary
Diseases Atrial Fibrillation (AF):
• Chronic systemic interventions
• Microbial shifts associated
inflammation to modulate
with systemic inflammation (Gawałko et
• Influencing atrial TMAO levels
and electrophysiological al., 2022)
remodeling in AF
disturbances

Colorectal Cancer: • Creation of a

• Enrichment of oncogenic pro-inflammatory (Ranjbar et

• Diet-based
bacteria (Fusobacterium microenvironment al., 2021)
strategies
nucleatum) • Promotion of
• Microbiome
• Reduction of protective genomic
Cancers profiling for
commensals instability and
targeted
Pancreatic Cancer (and tumorigenesis
therapeutic
others): • Modulation of (Panebianco
interventions
• Altered bile acid metabolism host immune et al., 2022)

and inflammatory profiles responses

 Mechanistic Therapeutic Reference
Disease State Dysbiotic Features
Implications Approaches

• Impaired
• Fecal
epithelial barrier
microbiota
function resulting
Inflammatory Bowel Disease transplantation
in increased
(IBD): (FMT)
intestinal
• Loss of protective species • Probiotics
permeability (Zhao et al.,
Autoimmune & (e.g., F. prausnitzii) and targeted
• Chronic, 2021)
Inflammatory • Reduced diversity microbiome
dysregulated
Diseases Rheumatoid Arthritis (RA) modulation
immune activation
and Atopic Dermatitis (AD): • Early-life
• Systemic (Yang et al.,
• Overrepresentation of pro- interventions
inflammation 2024)
inflammatory taxa to promote
driving extra
immune
intestinal
tolerance
manifestations
3 Methodology and Literature Selection

1. First, biological samples usually feces are collected by sterile sampling to avoid

contamination and stored by techniques like cryopreservation (Marotz et al., 2021),

ethanol, or commercial buffers (e.g., OMNIgene.GUT (Song et al., 2016)) to maintain

microbial integrity. DNA is extracted by mechanical and/or chemical lysis techniques,

and kits like QIAamp or Power Soil are used for maximum yield and purity (Szopinska et

al., 2018). The target regions of the 16S rRNA gene are amplified by PCR using high-

fidelity enzymes and appropriate primers. High-throughput sequencing platforms like

Illumina MiSeq (Caporaso et al., 2012) or PacBio are then utilized (Wagner et al., 2016) .

Lastly, bioinformatics pipelines like QIIME2, DADA2 are used for quality control,

OTU/ASV classification, taxonomic assignment, and diversity analysis (Marizzoni,

Gurry, et al., 2020). Standardization and consistency across all the steps are crucial to

reduce biases and batch effects (Combrink et al., 2023).

2. The research approach of gut microbiome analysis is grounded on the employment of

cutting-edge and innovative technologies. The principal methods are culturomics (high-

throughput culturing of bacteria) (Browne et al., 2016), metagenomics (amplicon and

shotgun sequencing), and multi-omics strategies such as meta transcriptomic,

metabolomics, and IgA-Seq. Moreover, in vitro models such as SHIME®, HuMix, and

Rapid AIM mimic the human gut environment to investigate host–microbe interactions.

These methods unveil the composition, function, and interactions of gut microbes with

the host, which is beneficial for diagnostics as well as microbiome-targeted therapy (Kwa

et al., 2023).
3. Smmary of Gut Microbiome Analysis and Dysbiosis Methodology: (Gnatzy et al., 2023)
4. Methodology of Neurodegeneration Analysis and Treatment: (Shusharina et al., 2023)
3.1 Technological Advances in Microbiome Profiling

1. Bioinformatics software such as QIIME2 (Bolyen et al., 2019), DADA2 (Prodan et al.,

2020), MetaPhlAn2 (Truong et al., 2015), and MEGAN (Huson & Mitra, 2012) are

crucial in microbiome data analysis, such as OTU/ASV determination and taxonomic

profiling. Shotgun metagenomics offers strain-level resolution and functional gene data

but is computationally expensive and pricey. Software such as MEGAHIT, Kraken2, and

HUMAnN3 are useful in assembly and functional annotation. Machine learning models

such as random forests, neural networks, and K-nearest neighbors improve the predictive

power of dysbiosis and forensic metrics such as post-mortem intervals. These methods

handle complex, high-dimensional microbiome data and are therefore robust for forensic

diagnosis and personal health monitoring (Zhang et al., 2023).

4 Conclusion:

Recent advances in high-throughput sequencing and metagenomics analysis have significantly

expanded our understanding of the gut microbiome and its role in human disease. The review

highlights that dysbiosis a polyvalent perturbation of microbial function and composition is a

unifying underlying cause of a broad range of conditions, including metabolic disorders,

neurodegenerative disorders, cardiovascular disease, cancers, and autoimmune or inflammatory

disorders. Despite significant progress, our ability to define a "healthy" microbiome remains

vague, largely because of inter-individual heterogeneity and complex host-microbial interactions.

Of special interest, mechanistic insight elucidates that changes in microbial metabolism, immune

modulation, and integrity of the gut barrier play pivotal roles in pathogenesis of disease.

Furthermore, recent findings suggest the possibility of targeted interventions in the microbiome,

such as the use of probiotics, prebiotics, symbiotic, and fecal microbiota transplantation, as
potential strategies in the restoration of microbial balance and the stoppage of disease

progression. Nevertheless, the current controversies surrounding causality versus correlation, and

the heterogeneity noted in response to therapy, underscore the need for additional longitudinal

and mechanistic studies. In the end, a better understanding of gut microbiome dysbiosis will

facilitate personalized medicine approaches to enhance diagnostic accuracy and therapeutic

efficacy in the treatment of complex disease.

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