The educational content in this post, elaborated in collaboration with Bromatech, was independently developed and approved by the GMFH publishing team and editorial board.

Besides diet and exercise, gut microbes could contribute to making you thin

Diet and exercise remain the first interventions for weight loss, but variability response between individuals is observed and it’s common that most people end up regaining the weight they lost within two years. The gut ecosystem could partially explain this and emerging evidence suggests that targeting the gut could help to move forward. One of the theories on the roots of obesity, with evidence from both mice and humans, incorporates the gut microbiota and inflammation1,2.

In recent years, scientists have explored how our tiny microbes living in the gut contribute to our metabolism and body weight regulation. Initial findings showed that germ-free mice present a reduction in body fat whereas mice receiving the microbiota of an obese twin increased their body weight more than the mice receiving that of a lean twin and this was not explained by the number of calories in the mice diet. That said such findings are not always consistently confirmed and “resetting” the gut microbiota through fecal microbiota transfer in patients who undergo bariatric surgery does not appear to affect weight loss3.

In reference to the challenge in defining a healthy gut microbiota, research revealed no consistent gut microbiota differences between lean people and people with obesity4 and no clear role of the early-life gut microbiota towards risk of obesity in later life5. However, it turns out that gut microbiota is involved in metabolic health, such as blood glucose control and food intake behavior, explaining why not all people lose weight when they change their lifestyle.

 

New clues into how gut bacteria control your food preferences

Scientists have suggested that an imbalanced gut microbiome composition and metabolites are causally involved in inappropriate food behaviors, including alterations in palatable food preferences and food-seeking behavior observed in obesity 6,7. A new study adds preliminary evidence for the idea that gut microbes could affect food behaviors through shaping the dopamine neurotransmission in brain areas involved in food reward8,9. A mechanistic hypothesis includes gut microbes-mediated activation of neuroinflammation since high-fat diet feeding increases plasma levels of lipopolysaccharide (LPS), a component found in the outer membrane of some bacteria, leading to inflammation including in the brain. The researchers showed that such bacterial component can trigger food-reward dysregulation when it reaches the brain which ultimately results in alterations of preference towards palatable food and food-seeking behaviors8.

What is also interesting is that receptors in the lining of the gut modulate the levels of a key microbial metabolite, ultimately influencing the brain’s sugar preference. It turned out that, in mouse models and people, intestinal free fatty acid receptor 4 (Ffar4) regulates the abundance of Bacteroides vulgatus, which produces the metabolite pantothenate (pantothenic acid or vitamin B5) that induces secretion of the hormones GLP1 in the gut and FGF21 in the liver, which act on the hypothalamus to reduce sugar intake. Interestingly, the levels of B. vulgatus are decreased in diabetic mice and humans. As GLP-1 alone did not affect sugar preference and the liver production of FGF21 hormone was a mandatory step, these findings highlight that the brain-gut connection is not solely involved but also a gut-liver-brain axis10. These findings suggest that gut bacteria can drive sugar cravings, leading to the increased consumption of sugary foods, which is seen in obesity.

In line with these findings, previous research in mice also revealed that other gut microbial species (e.g., Faecalibacterium prausnitzii and Bacteroides uniformis) or their metabolites can reduce overfeeding11,12. This supports that overconsumption could be modulated by the gut microbiome13.

 

People with obesity-related disorders may benefit from gut microbiota-targeted dietary interventions

While the first intervention to tackle obesity is a healthy diet and sufficient exercise, recent human studies suggest that people suffering from obesity may benefit from dietary and supplemental interventions that specifically act on the microbiome:

  • Lactobacillus and Bifidobacterium-containing probiotics: Lactobacillus species have been the most studied probiotics for obesity, and the beneficial effects of such probiotics on body weight and body fat in overweight individuals seem to be strain dependent14. Several studies have demonstrated that supplementation with Bifidobacterium breve B-3 in individuals with a BMI between 25 and 30 over a 12-week period led to a reduction in fat mass and waist circumference, as well as an increase in serum HDL levels15,16. Moreover, two studies conducted by the Autonomous University of Madrid investigated the synergistic effects of a hypocaloric Mediterranean-type diet combined with the administration of a probiotic mixture composed of Bifidobacterium breve B-3, Lactobacillus plantarum LP-115, and Lactobacillus acidophilus LA14 in patients with class I obesity (30<BMI<34.9), compared to diet alone. Results indicated that the intervention group experienced a statistically significant reduction in anthropometric and blood parameters associated with cardiovascular risk, as well as a significant increase in bacterial species inversely associated with overweight and/or obesity, such as Bifidobacterium, Faecalibacterium spp., and Akkermansia muciniphila17,18.
  • Next-generation beneficial microbes: bacteria with promising benefits for weight loss and glycaemic control include Akkermansia muciniphila, Hafnia alveiHA4597TM and Eubacterium hallii19. The main mechanisms of action involved include a restoration of gut barrier and an improvement in insulin sensitivity, a reduction in total cholesterol, and decrease of several markers of inflammation and liver dysfunction. The potential benefits of Hafnia alvei seems to involve the synthesis of a protein capable to modulate perception of satiety at the brain level20,21.
  • Type 2 resistant-starch prebiotic fiber: consuming 40 g per day of prebiotic resistant starch over 8 weeks led to lower body weight, lower visceral fat mass, lower lipid absorption (as supported by an increased fecal lipid content), and an enrichment of Bifidobacterium adolescentis, which is a primary degrader of resistant starch, as compared to a non-prebiotic control starch22.

Beyond boosting beneficial gut commensals and strengthening the gut barrier, some additional dietetic advice may help manage weight. A study, of more than 100,000 people, supports a diet providing primarily plant-based foods, unprocessed foods, with a moderate intake of animal-based foods, is associated with healthy ageing without chronic cardiovascular diseases23. Intermittent fasting, especially time-restricted eating, was also effective for weight loss in adults with overweight or obesity24.

It also seems reasonable to reduce marketing campaigns that boost unhealthy food. In this context, it seems prudent to limit artificial sweeteners and sugar-sweetened foods as much as possible, even in individuals who are physically active25. This recommendation is based on recent findings in mice and humans showing that sugar and some artificial sweeteners may trigger inflammation and are linked with an increased risk of type 2 diabetes25-27.

 

Takeaway

  • While diet and exercise remain the go-to interventions for weight loss, an appropriate modulation of the gut microbiome could also help in weight management.
  • Gut bacteria can drive sugar cravings, leading to the increased consumption of sugary foods seen in obesity.
  • While the first treatment for obesity is a healthy diet and sufficient exercise, some probiotics and novel beneficial microbes and resistant-starch prebiotic fibers could help tackle excessive weight.

 

References:

  1. Liu BN, Liu XT, Liang ZH, et al. Gut microbiota in obesity. World J Gastroenterol. 2021; 27(25):3837-3850. doi: 10.3748/wjg.v27.i25.3837.
  2. Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019; 25(12):1822-1832. doi: 10.1038/s41591-019-0675-0.
  3. Lahtinen P, Juuti A, Luostarinen M, et al. Effectiveness of fecal microbiota transplantation for weight loss in patients with obesity undergoing bariatric surgery. JAMA Netw Open. 2022; 5(12):e2247226. doi: 10.1001/jamanetworkopen.2022.47226.
  4. Castaner O, Goday A, Park YM, et al. The gut microbiome profile in obesity: a systematic review. Int J Endocrinol. 2018; 4095789. doi: 10.1155/2018/4095789.
  5. Egeø Poulsen C, Vinding R, Rasmussen MA, et al. No association between the early-life gut microbiota and childhood body mass index and body composition. Med. 2024; 100538. doi: 10.1016/j.medj.2024.10.015.
  6. de Wouters d’Oplinter A, Verce M, Huwart SJP, et al. Obese-associated gut microbes and derived phenolic metabolite as mediators of excessive motivation for food reward. Microbiome. 2023; 11(1):94. doi: 10.1186/s40168-023-01526-w.
  7. de Wouters d’Oplinter A, Rastelli M, Van Hul M, et al. Gut microbes participate in food preference alterations during obesity. Gut Microbes. 2021; 13(1):1959242. doi: 10.1080/19490976.2021.1959242.
  8. Huwart SJP, Fayt C, Gangarossa G, et al. TLR4-dependent neuroinflammation mediates LPS-driven food-reward alterations during high-fat exposure. J Neuroinflammation. 2024; 21(1):305. doi: 10.1186/s12974-024-03297-z.
  9. Kim JS, Williams KC, Kirkland RA, et al. The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab. 2023; 75:101764. doi: 10.1016/j.molmet.2023.101764.
  10. Zhang T, Wang W, Li J, et al. Free fatty acid receptor 4 modulates dietary sugar preference via the gut microbiota. Nat Microbiol. 2025; 10(2):348-361. doi: 10.1038/s41564-024-01902-8.
  11. Fan S, Guo W, Xiao D, et al. Microbiota-gut-brain axis drivers overeating disorders. Cell Metab. 2023; 35(11):2011-2027.e7. doi: 10.1016/j.cmet.2023.09.005.
  12. Agustí A, Campillo I, Balzano T, et al. Bacteroides uniformis CECT 7771 modulates the brain reward response to reduce binge eating and anxiety-like behavior in rat. Mol Neurobiol. 2021; 58(11):4959-4979. doi: 10.1007/s12035-021-02462-2.
  13. Fasano A. The physiology of hunger. N Engl J Med. 2025; 392(4):372-381. doi: 10.1056/NEJMra2402679.
  14. Crovesy L, Ostrowski M, Ferreira DMTP, et al. Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled trials. Int J Obes. 2017; 41(11):1607-1614. doi: 10.1038/ijo.2017.161.
  15. Minami JI, Kondo S, Yanagisawa N, et al. Oral administration of Bifidobacterium breve B-3 modifies metabolic functions in adults with obese tendencies in a randomised controlled trial. J Nutr Sci. 2015; 4:e17. doi: 10.1017/jns.2015.5.
  16. Minami J, Iwabuchi N, Tanaka M, et al. Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults: a randomized, double-blind, placebo-controlled trial. Biosci Microbiota Food Health. 2018; 37(3):67-75. doi: 10.12938/bmfh.18-001.
  17. Lorenzo O, Crespo-Yanguas M, Hang T, Lumpuy-Castillo J, Hernández AM, Llavero C, García-Alonso M, Ruiz-Tovar J. Addition of Probiotics to Anti-Obesity Therapy by Percutaneous Electrical Stimulation of Dermatome T6. A Pilot Study. Int J Environ Res Public Health. 2020 Oct 3;17(19):7239.
  18. Parascinet, O.; Mas, S.; Hang, T.; Llavero, C.; Lorenzo, Ó.; Ruiz-Tovar, J. A Pilot Study: The Reduction in Fecal Acetate in Obese Patients after Probiotic Administration and Percutaneous Electrical Neurostimulation. Nutrients 2023, 15, 1067.
  19. Vallianou NG, Kounatidis D, Tsilingiris D, et al. The role of next-generation probiotics in obesity and obesity-associated disorders: current knowledge and future perspectives. Int J Mol Sci. 2023; 24(7):6755. doi: 10.3390/ijms24076755.
  20. Zhang Y, Liu R, Chen Y, et al. Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut. Cell Metab. 2025; 37(3):592-605.e6. doi: 10.1016/j.cmet.2024.12.010.
  21. Bakshani CR, Ojuri TO, Pilgaard B, et al. Carbohydrate-active enzymes from Akkermansia muciniphila break down mucin O-glycans to completion. Nat Microbiol. 2025; 10(2):585-598. doi: 10.1038/s41564-024-01911-7.
  22. Li H, Zhang L, Li J, et al. Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota. Nat Metab. 2024; 6(3):578-597. doi: 10.1038/s42255-024-00988-y.
  23. Tessier AJ, Wang F, Ardisson Korat A, et al. Optimal dietary patterns for healthy aging. Nat Med. 2025. doi: 10.1038/s41591-025-03570-5.
  24. Hua Z, Yang S, Li J, et al. Intermittent fasting for weight management and metabolic health: An updated comprehensive umbrella review of health outcomes. Diabetes Obes Metab. 2025; 27(2):920-932. doi: 10.1111/dom.16092.
  25. Pacheco LS, Tobias DK, Haslam DE, et al. Sugar-sweetened or artificially sweetened beverage consumption, physical activity and risk of type 2 diabetes in US adults. Diabetologia. 2025; 68(4):792-800. doi: 10.1007/s00125-024-06351-w.
  26. Zhang Y, Luo K, Peters BA, et al. Sugar-sweetened beverage intake, gut microbiota, circulating metabolites, and diabetes risk in Hispanic Community Health Study/Study of Latinos. Cell Metab. 2025; 37(3):578-591.e4. doi: 10.1016/j.cmet.2024.12.004.
  27. Wu W, Sui W, Chen S, et al. Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. Cell Metab. 2025; S1550-4131(25)00006-3. doi: 10.1016/j.cmet.2025.01.006.