# The Gut–Brain Axis in Obesity: Mechanisms, Development, and Therapeutic Perspectives

**Authors:** Laura Arellano-García, María P. Portillo, Anna Hadjihambi, J. Alfredo Martínez, Iñaki Milton-Laskibar

PMC · DOI: 10.1007/s13668-026-00732-w · Current Nutrition Reports · 2026-02-26

## TL;DR

This review explores how gut microbiota and gut-brain communication contribute to obesity and how treatments might restore these systems.

## Contribution

The paper provides a comprehensive analysis of gut-brain axis mechanisms in obesity and potential therapeutic strategies.

## Key findings

- Gut microbiota dysbiosis is linked to the development of obesity.
- Microbial metabolites like SCFAs influence gut-brain communication.
- Lifestyle changes and bioactives may restore gut-brain axis function in obesity.

## Abstract

This narrative review analyses the implication of obesity-associated gut microbiota dysbiosis, as well as the associated impairments in gut-brain axis communication, in the onset and development of this chronic metabolic disease.

Gut microbiota dysbiosis, which is a common feature in individuals with obesity, is considered among the factors leading to its development. In fact, dietary habits not only modulate the composition of gut microbiota, but also the release of microbe-derived metabolites such as SCFAs, which in turn participate in the gut-brain axis communication. Interestingly, the approaches often used for obesity management, including lifestyle modification-based interventions, pharmacotherapy or the usage of bioactives (such as phenolic compounds or probiotics) have also been shown to restore the impairments in gut-brain axis communication associated to this disease. In this regard, the recovery of gut microbiota eubiosis and improvement of the intestinal barrier function, as well as the modulation of microbial metabolite production, have been described as potential underlying mechanisms of action.

The review highlights the importance of the gut-brain axis in obesity, both in the development as well as the management of this chronic metabolic disease. However, further research is warranted in order to corroborate the current findings and to better elucidate the mechanisms underlying this complex signalling network. Doing so, valuable information that will pave the way for the development of more specific and effective obesity treatments may be obtained.

## Linked entities

- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, PYY (peptide YY) [NCBI Gene 5697] {aka PYY-I, PYY1}, Ffar1 (free fatty acid receptor 1) [NCBI Gene 233081] {aka Gpr40}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, Agrp (agouti related neuropeptide) [NCBI Gene 11604] {aka Agrt, Art}, CCK (cholecystokinin) [NCBI Gene 885], Ffar3 (free fatty acid receptor 3) [NCBI Gene 233080] {aka Gm478, Gpr41}, UCP1 (uncoupling protein 1) [NCBI Gene 7350] {aka SLC25A7, UCP}, Mc4r (melanocortin 4 receptor) [NCBI Gene 17202] {aka Mc4-r, Pkcp}, Lepr (leptin receptor) [NCBI Gene 16847] {aka B219, LEP-R, LEPROT, Leprb, Modb1, OB-RGRP}, Glp1r (glucagon-like peptide 1 receptor) [NCBI Gene 14652] {aka GLP-1R, GLP1Rc}, Cck (cholecystokinin) [NCBI Gene 12424], MC4R (melanocortin 4 receptor) [NCBI Gene 4160] {aka BMIQ20}, Hcrt (hypocretin) [NCBI Gene 15171] {aka PPOX}, Pomc (pro-opiomelanocortin-alpha) [NCBI Gene 18976] {aka ACTH, BE, Beta-LPH, Clip, Gamma-LPH, Npp}, Ghrl (ghrelin) [NCBI Gene 58991] {aka 2210006E23Rik, Ghr, MTLRP, MTLRPAP, m46}, Pphln1 (periphilin 1) [NCBI Gene 223828] {aka CR, HSPC206, HSPC232}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, AHSG (alpha 2-HS glycoprotein) [NCBI Gene 197] {aka A2HS, AHS, APMR1, FETUA, HSGA}, Pyy (peptide YY) [NCBI Gene 217212], Bax (BCL2-associated X protein) [NCBI Gene 12028], Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Ffar2 (free fatty acid receptor 2) [NCBI Gene 233079] {aka GPCR43, Gpr43}, Trpv1 (transient receptor potential cation channel, subfamily V, member 1) [NCBI Gene 193034] {aka OTRPC1, TRPV1alpha, TRPV1beta, VR-1, Vr1}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, Cartpt (CART prepropeptide) [NCBI Gene 27220] {aka Cart}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, Npy (neuropeptide Y) [NCBI Gene 109648] {aka 0710005A05Rik}, Gcg (glucagon) [NCBI Gene 14526] {aka GLP-1, Glu, PPG}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, GAST (gastrin) [NCBI Gene 2520] {aka GAS}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}
- **Diseases:** endotoxemia (MESH:D019446), hypertension (MESH:D006973), cardiovascular disease (MESH:D002318), infections (MESH:D007239), brain inflammation (MESH:D004660), gastrointestinal disorders (MESH:D005767), weight (MESH:D015431), insulin resistance (MESH:D007333), food allergies (MESH:D005512), T2D (MESH:D003924), adiposity (MESH:D018205), steatotic liver (MESH:D017093), visceral obesity (MESH:D056128), CR (MESH:D002313), infectious complications (MESH:D003141), inflammation (MESH:D007249), MASLD (MESH:D008107), metabolic disturbances (MESH:D024821), dysbiosis (MESH:D064806), diabetes (MESH:D003920), neuroinflammation (MESH:D000090862), weight gain (MESH:D015430), Obesity (MESH:D009765), overweight (MESH:D050177), body-weight loss (MESH:D001835), metabolic disease (MESH:D008659)
- **Chemicals:** CP1563 (-), N-oleoylethanolamine (MESH:C033595), 5-HIAA (MESH:D006897), valeric acid (MESH:C038780), Oligofructose (MESH:C120489), orlistat (MESH:D000077403), catecholamines (MESH:D002395), butyrate (MESH:D002087), muramyl dipeptide (MESH:D000119), propionate (MESH:D011422), amine (MESH:D000588), naltrexone (MESH:D009271), xylooligosaccharide (MESH:C570991), carbohydrate (MESH:D002241), malondialdehyde (MESH:D008315), 10-Hydroxy-cis-12-octadecenoic acid (MESH:C000629086), fructose (MESH:D005632), polyphenol (MESH:D059808), Prebiotics (MESH:D056692), butyric acid (MESH:D020148), LPS (MESH:D008070), sucrose (MESH:D013395), lipid (MESH:D008055), endocannabinoids (MESH:D063388), inulin-propionate ester (MESH:C000634130), acetate (MESH:D000085), dopamine (MESH:D004298), PBS (MESH:D007854), topiramate (MESH:D000077236), 5-HT (MESH:D012701), glucose (MESH:D005947), SCFA (MESH:D005232), ROS (MESH:D017382), fat (MESH:D005223), linoleic acid (MESH:D019787), ibuprofen (MESH:D007052), ezetimibe (MESH:D000069438), 2-oleoylglycerol (MESH:C505247), gallic acid (MESH:D005707), polysaccharides (MESH:D011134), cortisol (MESH:D006854), bupropion (MESH:D016642), TG (MESH:D014280), fructooligosaccharides (MESH:C116580), lipoteichoic acids (MESH:C009900), epinephrine (MESH:D004837), l (MESH:D007930), 2'-fucosyllactose (MESH:C031420), Phentermine (MESH:D010645), luminal (MESH:D010634), metformin (MESH:D008687), GABA (MESH:D005680), norepinephrine (MESH:D009638), glutamate (MESH:D018698), inulin (MESH:D007444), ethanol (MESH:D000431), cholesterol (MESH:D002784), QA (MESH:D017378)
- **Species:** Akkermansia muciniphila (species) [taxon 239935], Lactobacillus amylovorus (species) [taxon 1604], Echinophyllia sp. EC (species) [taxon 465054], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Lactobacillus johnsonii (species) [taxon 33959], Lactococcus (lactic streptococci, genus) [taxon 1357], Clostridium (genus) [taxon 1485], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606], Parasutterella (genus) [taxon 577310], Enterobacteriaceae (enterobacteria, family) [taxon 543], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Blautia (genus) [taxon 572511], Bifidobacterium longum (species) [taxon 216816], Eubacterium (genus) [taxon 1730], Hibiscus sabdariffa (red-sorrel, species) [taxon 183260], Mus musculus (house mouse, species) [taxon 10090], Coprococcus (genus) [taxon 33042], Lacticaseibacillus rhamnosus (species) [taxon 47715], Pseudomonadota (proteobacteria, phylum) [taxon 1224], Roseburia (genus) [taxon 841], Allobaculum (genus) [taxon 174708], Lacticaseibacillus paracasei (species) [taxon 1597], Bacteroides sp. (species) [taxon 29523], Enterobacterales (order) [taxon 91347], Ruminococcus (genus) [taxon 1263]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12946278/full.md

## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC12946278/full.md

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Source: https://tomesphere.com/paper/PMC12946278