An update on the role of prebiotics and probiotics in controlling obesity

Obesity currently affects up to 650 million people worldwide and this figure has doubled since 1980. Of the environmental factors that may contribute to the development of obesity, gut microbiota is in the spotlight, given that it may be involved in the low-grade inflammatory process and subsequent disrupted glucose metabolism and fat absorption that are features of obesity.

Epidemiological research has linked gut microbiota to the state of an individual’s metabolic health. A first study with a cohort of 292 non-obese and obese individuals showed that individuals with a low bacterial richness were characterized by more marked overall adiposity, more weight gain over time, insulin resistance and dyslipidemia when compared with individuals showing high bacterial richness. High gene count individuals also showed an enrichment in anti-inflammatory species such as Faecalibacterium prausnitzii, whereas low gene count individuals had a higher prevalence of potentially pro-inflammatory bacteria, such Bacteroides and Ruminococcus gnavus. It should be taken into account that in addition to the hypothesis regarding the causative role of microbiota in obesity, this dysbiosis may be the result of adaptation to a high-fat and high-sugar diet.

Recent analyses (here; here) have shown high inter-individual differences in particular bacterial groups related to obesity and these data highlight the difficulty in finding a simple taxonomic signature of obesity in the gut microbiome and predicting the most important factor driving human weight change.

Most of the research so far has been conducted in animal models of diet-induced obesity, whereas human studies with the specific aim of obesity management have also been published, albeit in a limited number.

Preclinical evidence has reported reductions in weight gain and, in particular, fat tissue mass at different locations following the administration of probiotics. The mechanisms involved in many experimental studies include effects on body weight, fat, glucose and lipid metabolism, inflammation and liver steatosis, among others. The high-fat diets in experimental models employed for the study of the effects of probiotics on obesity may be a confounding factor and some mice studies have induced obesity by other means, including a genetic model of obesity and monosodium glutamate-induced obesity.

When managing obesity with probiotics, time of administration matters and the early-life period seems to be a critical time for targeting gut microbiota and preventing obesity-related disorders later in life. In this context, it is worth mentioning a new mice study, led by Dr. Jan Knol from the Laboratory of Microbiology at Wageningen University (The Netherlands), that has analyzed whether a synbiotic intervention in early life could affect metabolic health in adulthood. The researchers administered mice either prebiotics (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides in ratio 9:1) or synbiotics (scGOS/lcFOS in a ratio 9:1 plus 1 x 10⁹ colony-forming units of Bifidobacterium breve M-16 V) until post-natal day 42 and they were subsequently challenged with a high-fat Western-style diet (40% energy from fat) for 8 weeks. Early life synbiotics protected mice against Western-style diet-induced excessive fat accumulation at post-natal days 70 and 98 and led to improvements in metabolism, including glucose (homeostatic model assessment of insulin resistance) and lipid homeostasis (reduced liver weight and decreased hepatic triglyceride content) at post-natal day 98. In terms of the mechanisms involved, the synbiotics affected the ileum’s cholesterol metabolism on post-natal day 98. Specifically, gene sets related to cholesterol biosynthesis were up-regulated in adult mice with synbiotic supplementation in early life (compared with the control group), whereas genes related to cholesterol storage, distribution and excretion were down-regulated in the synbiotic group. Changes in fecal microbiota composition, both in early life and in adulthood, included an increased abundance of Bifidobacterium. Taken together, these experimental data suggest the potential of synbiotic interventions in early life as a preventive measure to lower the risk of obesity and improve metabolic health during adulthood.

In humans, the number of studies focusing on probiotic and prebiotic administration for obesity management is still very low and there are mixed results (here; here) on whether probiotics and prebiotics could decrease obesity outcomes by modulating the gut microbiome. The most prominent effects of probiotics on host metabolism have been reported basically for Lactobacillus and/or Bifidobacterium strains and/or specific prebiotic fibers, and studies until now suggest their consumption could provide protection from the likelihood of becoming obese rather than as obesity treatment. The general limitations of probiotic trials were small sample sizes and an absence of longer-term follow up.

In conclusion, the majority of the research supporting the role of probiotics and prebiotics in obesity management comes from experimental studies. In humans, further research could help guide which populations could benefit from the protective effects of probiotics and prebiotics against obesity. Several potential influential environmental and intrinsic factors may affect the relationship between changes in gut microbiota and changes in weight induced by microbiota-targeted interventions and they should be considered for future studies.

References:

Walters WA, Xu Z, Knight R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett. 2014; 588(22):4223-33. doi: 10.1016/j.febslet.2014.09.039.

Sze MA, Schloss PD. Looking for a signal in the noise: revisiting obesity and the microbiome. MBio. 2016; 7(4). doi: 10.1128/mBio.010018-16.

Mischke M, Arora T, Tims S, et al. Specific synbiotics in early life protect against diet-induced obesity in adult mice. Diabetes Obes Metab. 2018. doi: 10.1111/dom.13240.

Jones RB, Alderete TL, Martin AA, et al. Probiotic supplementation increases obesity with no detectable effects on liver fat or gut microbiota in obese Hispanic adolescents: a 16-week, randomized, placebo-controlled trial. Pediatr Obes. 2018. doi: 10.1111/ijpo.12273.