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Cui et al. Microbiome Res Rep. 2025;4:31 https://dx.doi.org/10.20517/mrr.2025.25 Page 3 of 14

Similarly, antibiotic treatment of conventional mice leads to reduced weight gain under HFD conditions,
and the recolonization of germ-free or antibiotic-treated mice with microbiota derived from either obese or
lean donors successfully transfers the corresponding adiposity phenotypes to the recipients, thereby
establishing a direct causal link between gut microbial composition and host fat accumulation [18,21] . FMT
experiments provide additional evidence for this causality: germ-free or antibiotic-treated mice that receive
fecal material from obese donors develop increased white adipose tissue mass, enlarged adipocytes, and
impaired insulin sensitivity . In contrast, transplantation with microbiota from lean donors protects mice
[1,7]
from HFD-induced obesity and its associated metabolic disturbances [18,21] . These observations highlight the
critical influence of microbiota-derived signals on systemic energy metabolism. Beyond the structural
composition of the gut microbiota, specific microbial metabolites serve as key effectors that modulate host
lipid metabolism via diverse signaling pathways. Acetate, one of the primary SCFAs, acts as a substrate for
hepatic de novo lipogenesis, whereas propionate has been found to inhibit hepatic cholesterol synthesis.
Butyrate, in turn, plays a distinct role by enhancing mitochondrial function in brown adipose tissue, thereby
promoting fatty acid oxidation and thermogenesis, which contributes to increased energy expenditure [13,22] .
Collectively, the findings from these murine studies illustrate a complex and robust mechanistic framework
in which dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes ratio, increased SCFA production,
and shifts in microbial metabolic output, directly contributes to pathological fat accumulation and
metabolic dysfunction. This body of evidence underscores the gut microbiota’s essential role in regulating
fat deposition and its potential as a therapeutic target for obesity and related metabolic disorders.

Specific microbiota in pigs and chickens
Distinct pig breeds harbor characteristic gut microbiota compositions that are closely associated with breed-
specific fat deposition traits [23,24] . For instance, the Chinese indigenous Ningxiang pig, known for its high
IMF content, possesses a cecal microbiota enriched in Lactobacillus and branched-chain amino acid
[25]
(BCAA) metabolic pathways . Transplantation of Lactobacillus reuteri isolated from Ningxiang pigs into
lean Duroc × Landrace × Yorkshire (DLY) pigs or rats significantly increases circulating BCAA levels and
IMF accumulation, highlighting a causal role for this microbial consortium in lipid deposition [23,25] .
Moreover, FMT from obese Ningxiang pigs into lean DLY pigs remodels the recipient’s gut microbial
community and downregulates the expression of the carnitine transporter SLC22A5 in skeletal muscle,
thereby reducing fatty acid oxidation and promoting lipid accumulation . Comparative analyses further
[23]
reveal that native breeds such as Laiwu or Tibetan pigs display higher microbial diversity and unique taxa
enriched in lipid-associated pathways compared to commercial breeds (e.g., Duroc, Landrace, Large White),
which tend to harbor gut communities dominated by carbohydrate-fermenting bacteria (e.g., Clostridium,
Catenibacterium) and methanogens - features that may underlie differences in energy utilization efficiency
and backfat thickness [26,27] . Additionally, gut microbiota composition undergoes dynamic shifts across
developmental stages, with lactating piglets dominated by lactic acid bacteria and Bifidobacterium, while
post-weaning stages show a rapid increase in fiber-degrading genera such as Prevotella and Roseburia,
which in turn modulate host lipid metabolism [28,29] . Importantly, gut microbiota appears to regulate fat
deposition in a depot-specific manner; certain microbial taxa and metabolites (e.g., SCFAs) influence
subcutaneous fat (e.g., backfat thickness) and IMF differently, through modulation of host lipid metabolism
[29]
genes such as LPL and ANGPTL4 . For example, obese-type pigs exhibit elevated LPL expression and
reduced ANGPTL4 levels in muscle, promoting IMF accumulation, while Lactobacillus reuteri from
Ningxiang pigs modulates SLC22A5-mediated carnitine transport to enhance IMF specifically [23,29] .
Together, these findings underscore the breed-, stage-, and depot-specific roles of the gut microbiota in
regulating porcine fat deposition and support the development of precision microbiota-targeted strategies
in swine production.