Integrative microbiome and functional profiling decodes pro-inflammatory gut microbiome signatures in South Indian patients with Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by α-synuclein aggregation in dopaminergic neurons. Emerging evidence implicates gut microbiota dysbiosis in PD-associated inflammation through the gut microbiota-brain axis (GMBA). As gut microbial composition varies geographically, population-specific studies are essential to understand this relationship.

The present study employed 16S rRNA gene amplicon sequencing to characterize the gut microbiome of PD patients and healthy controls (HCs) from Kerala. Significant differences in microbial diversity and taxonomic composition were observed. PD patients exhibited increased abundances of pro-inflammatory genera, including Akkermansia, Bifidobacterium, Escherichia-Shigella, Collinsella, Eggerthellaceae_insertae_sedis_genus, Intestinimonas, and Enterobacterales_unclassified, alongside reduced levels of anti-inflammatory genera such as Bacteroides, Lachnospira, Agathobacter, Prevotella, and Erysipelotrichaceae UCG-003.

Predictive functional profiling indicated alterations in pathways related to neurotransmitter metabolism, including dopaminergic, glutamatergic, and GABAergic metabolism, as well as amino acid, polyamine, nucleotide, and energy metabolism. Integrative network analysis further linked PD-enriched taxa with dysregulated metabolic pathways, suggesting functional interactions between microbial composition and metabolic potential. These findings provide the first comprehensive insights into gut microbial alterations in a South Indian PD cohort, identify candidate microbial signatures associated with PD, and offer an exploratory framework for future multi-omics studies to validate microbiome-related mechanisms in PD pathophysiology.

The authors gratefully acknowledge the financial support provided by the Indian Council of Medical Research (ICMR), Government of India, through a Grant-in-Aid (Grant ID: No. 5/4-5/194/Neuro/2019-NCD-1). The authors sincerely thank all the study participants and their family members for their invaluable cooperation and support throughout the study. The authors also thank Gangadhara Sharma from the Comprehensive Care Centre for Movement Disorders (CCCMD), SCTIMST, for his technical assistance during the study.

The Open Access Fees for this article was fully covered by the One Nation One Subscription (ONOS) Initiative of Govt. of India (https://ror.org/036h6g940). Centre for Neuroscience, Department of Biotechnology, Cochin University for Science and Technology (CUSAT), Kochi, India Aneesa Painadath Alikunju, Dania Jose, Deepa Azhchath Vasu, Dayamrita K K & Baby Chakrapani P S Department of Biotechnology, Cochin University for Science and Technology (CUSAT), Kochi, India Aneesa Painadath Alikunju, Dayamrita K K & Baby Chakrapani P S Department of Biochemistry, Sree Sankara College, Ernakulam, India McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA National Centre for Polar and Ocean Research (NCPOR), Vasco da Gama, India Siddarthan Venkatachalam & Jabir Tajudeen Department of Neurology, Comprehensive Care Centre for Movement Disorders, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India Geetha Raman, Gayathri Thankam L, Divya K P & Syam Krishnan Department of Zoology, Union Christian College, Kochi, India Department of Applied Chemistry, Cochin University for Science and Technology (CUSAT), Kochi, India Narayanapillai Manoj & Baby Chakrapani P S Centre of Excellence in Neurodegeneration and Brain Health (CENABH), Kochi, India Correspondence to Aneesa Painadath Alikunju, Syam Krishnan or Baby Chakrapani P S. The authors declare no competing interests.

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