Impact of Ketogenic Diet on Gut Microbiota Composition and Short-Chain Fatty Acid Production in Central Indian Adults: A Case-Control Study

Background: The ketogenic diet (KD) has become widely accepted to treat metabolic disorders, but the processes on the composition of gut microbiota and metabolic output are not sufficiently described regarding non-Western populations. Gut microbiome has a decisive impact on health including immunity, metabolism, and systemic inflammation by generating short-chain fatty acids (SCFAs) and altering the gut-brain axis. The aim behind conducting this study is to judge the effect of an 8-week ketogenic diet on the diversity of gut microbiota, taxonomic and functional metabolic alterations in healthy Central Indian adults relative to a standard Indian diet (SID). Material and Methods: The case-control study involved 264 healthy adults (132 in KD group, 132 in control group) aged between 18-50 years having BMI, 18.5-29.9 kg/m 2 during Index Medical College between January 2023 and December 2024. The KD diet included 70, 20, 10 percent carbohydrates, fat, and protein respectively whereas the controls were fed on conventional Indian diet (55-60 percent carbohydrates, 20-25 percent fat, 15-20 percent protein). At baseline and weeks 8, stool samples underwent 16S rRNA gene sequencing (V3-V4 region, Illumina MiSeq) of the samples. Q IIME2 and DADA2 pipelines were used to analyze alpha diversity (Shannon index), beta diversity (PCoA), taxonomic abundance, and Firmicutes/Bacteroidetes (F/B) ratio. Results: alpha diversity (Shannon index: 3.45±0.38 to 3.12±0.35, p< 0.001) was significantly reduced in the KD group after 8 weeks, yet negligibly different in controls (3.44±0.39 to 3.43±0.38). Analysis of beta diversity showed that there was extensive community reorganization in the KD group (PCoA distance 0.28+0.07) compared to controls (0.04+0.02, p<0.001). KD taxonomically led to higher relative Firmicutes (52.1 6.5% to 58.3 6.8% p< 0.001) and lower Bacteroidetes (40.3 5.9% to 34.1 5.7% p< 0.001) and raised the F/B ratio relative to 1.29 -0.21 to 1.71 -0.25 (p< 0.001). There were no significant changes in taxonomic shifts in the control group. The KD group had specific improvement of Akkermansiamuciniphila and Parabacteroides. The alpha diversity was negatively associated with diet adherence in the KD group (r=-0.31, p<0.001) but not the control groups. Conclusion: 8-week ketogenic diet results in thorough gut microbiota restructuring and cannot be deemed healthy in Indian adults, such as diversity reduction, F/B ratio rise, and selective enrichment of fat-metabolic taxa. Although this has the potential to promote ketogenic metabolism and some other health-promising effects, the decrease of microbial diversity is a factor that should be taken seriously in the long-term use of KD. These discoveries offer new information on how microbiomes respond to KD in a non-Western ethnic with unique baseline dietary habits.

Keywords: Microbiota, ketogenic diet, gut microbiota, 16S rRNA sequencing, Firmicutes, Bacteroidetes, Indian population.