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Page 2 of 14 Cui et al. Microbiome Res Rep. 2025;4:31 https://dx.doi.org/10.20517/mrr.2025.25

INTRODUCTION
The gut microbiota, a dynamic ecosystem of trillions of bacteria, archaea, viruses, and fungi, orchestrates
[1,2]
host metabolism and energy homeostasis through its expansive metabolic repertoire . Dysbiosis,
characterized by shifts in community composition and function, has been strongly linked to aberrant fat
deposition and metabolic disorders such as obesity, type 2 diabetes (T2D), and non-alcoholic fatty liver
[3]
disease (NAFLD) . Emerging evidence highlights the gut-liver axis, microbial metabolites including short-
chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS), and immune crosstalk as central
mediators of lipid metabolism and inflammation . Germ-free and antibiotic-treated murine models have
[4,5]
been foundational: colonizing adult germ-free C57BL/6 mice with conventional microbiota induces up to a
60% increase in body fat and insulin resistance within two weeks despite reduced caloric intake, establishing
a causal link between microbes and fat deposition . Mechanistic studies reveal that gut microbes enhance
[1]
monosaccharide absorption and de novo hepatic lipogenesis via suppression of fasting-induced adipose
factor and increased adipocyte lipoprotein lipase (LPL) activity . Moreover, fecal microbiota
[6]
transplantation (FMT) from obese donors transfers adiposity to germ-free or antibiotic-treated recipients,
[1,7]
while lean donor FMT protects against high-fat-diet-induced weight gain . An elevated Firmicutes/
Bacteroidetes ratio commonly observed in obese states correlates with enhanced caloric extraction from
complex polysaccharides and increased fat mass in both mice and humans .
[3]

Concurrently, livestock research has harnessed microbiota manipulation to optimize fat deposition for meat
[8]
quality without compromising growth performance . In pigs, dietary interventions such as L-glutamate
supplementation in Shaziling breeds and targeted probiotic administration have increased intramuscular fat
(IMF) and modulated backfat thickness through specific shifts in microbial taxa . In broilers, succinate and
[9]
coated sodium propionate reshape cecal communities to reduce abdominal fat and enhance carcass
traits [10,11] . Furthermore, dietary components (e.g., fibers, probiotics) directly shape microbial composition
and function, establishing diet as a primary modulator of microbiota-mediated lipid metabolism across
species [12,13] . Together, these integrative findings from murine and agricultural models underscore the
translational potential of microbiota-based interventions for controlling fat deposition and mitigating
metabolic disorders across species .
[14]

MICROBIAL COMPOSITION AND FAT DEPOSITION
Obesity-associated dysbiosis in murine models
Obese murine models, including genetically obese ob/ob mice and those fed a high-fat diet (HFD),
consistently exhibit an elevated Firmicutes/Bacteroidetes ratio compared to their lean counterparts,
suggesting that this microbial shift enhances dietary energy harvest and promotes lipogenesis [15,16] . In
particular, the expansion of Firmicutes observed in ob/ob mice is associated with increased production of
SCFAs, such as acetate, propionate, and butyrate, which activate G protein-coupled receptors (GPCRs)
GPR41 and GPR43 on adipocytes . This activation contributes to adipocyte hypertrophy and greater fat
[17]
storage by influencing host lipid metabolism and hormonal regulation [13,18] . On the other hand, dietary
supplementation with fermentable fibers such as resistant starch and inulin has been shown to remodel the
gut microbiota toward SCFA-producing Bacteroidetes, resulting in decreased fat mass and improved
glucose tolerance in obese mice [19,20] , thus indicating a reversible aspect of diet-induced dysbiosis. Further
supporting the causal role of the microbiota in fat deposition, studies using germ-free C57BL/6 mice, which
lack all microbial colonization, have shown that these mice accumulate approximately 40% less total body
fat compared to conventional mice, despite consuming more calories . This finding implies that the
[1]
presence of gut microbiota facilitates more efficient extraction of dietary energy and promotes fat
[18]
accumulation .