Investigating novel approaches to combat obesity

Obesity has reached epidemic proportions in numerous countries around the globe and is a growing concern worldwide.¹

Obesity contributes to at least 2.8 million deaths annually because it is a major risk factor for a number of life-threatening chronic diseases, including metabolic syndrome, diabetes, cardiovascular disease and cancer.^2,3 There are a variety of efforts underway to control or reverse the development of obesity.

When a person consumes more energy than they use, the excess is laid down as fat. When the surplus fat deposits become excessive, a person is deemed obese, usually indicated by a bodyweight that is higher than 20% above their recommended weight. So, a key factor in the development of obesity is diet.

Diet has also been shown to influence the composition of the gut microbial community, with dietary alteration being quickly reflected in modifications in the microbes present in the gut.^4,5,6

The relationship between obesity and bacterial colonization of the gut has been widely investigated in the hope of discovering a novel strategy for the control of obesity. It is now clear that the human gut microbiota is a key factor in the development of obesity.

Gut microbiota and obesity

Typically, there are more than 100 trillion microscopic living organisms residing in the gastrointestinal tract, collectively referred to as the gut microbiome.⁷ Gut microbiota aid the healthy functioning of the gut, supplying energy and nutrients and combating infection.

In addition, the role gut microbiota helps to regulate host metabolism via their influence on energy storage, harvesting and expenditure, which implicates them in developing obesity.^8,9

Preclinical studies in mice models demonstrate that there is indeed a relationship between obesity and the activities of the gut microbiota.¹⁰ For instance, transplantation of the fecal microbiomes from an obese human adult to germ-free mice caused the mice to also lay down excessive fat.¹¹

In the same way, despite consuming more calories, germ-free mice are protected against obesity and are much leaner than normal control mice.¹²

Gut microbiota provides huge promise as a target for the management of obesity and obesity-related disorders, despite the exact mechanisms by which diet-induced changes in gut microbiota influence host appetite regulation and metabolism remain unconfirmed.¹³

Several different probiotic strains have demonstrated different beneficial anti-obesity influences, like improvements in insulin sensitivity, reduced body weight gain and reduced fat depots accumulation in rodents.¹⁴

For instance, the bacterial strain Bifidobacterium longum APC1472 has recently been shown to modulate ghrelinergic signaling, a pathway that is utilized to modulate central appetite regulation and metabolism, in vitro.¹⁵

Evaluating the effect of Bifidobacterium longum on fat metabolism

Atlantia Clinical Trials (Cork, Ireland) sponsored a recent study that investigated if B. longum APC1472 had an anti-obesity influence in mice fed a high-fat diet (HFD) to induce obesity.

The study also looked at whether supplementation of the human diet with B. longum APC1472 decreased body-mass index (BMI) in otherwise healthy overweight/obese individuals.¹⁶ In the mouse study, B. longum APC1472 was added to the drinking water of C57BL/6 mice receiving a high-fat diet for 16 weeks.

The HFD-fed mice that were administered B. longum APC1472 supplementation showed less fat depot accumulation, lower body weight and better glucose tolerance. Partial restoration of Bifidobacterium levels was the only alteration in microbiota composition.

For 12 weeks, otherwise healthy overweight/obese participants received B. longum APC1472 or placebo supplementation in the human intervention trial. No alteration was seen in BMI or waist-to-hip ratio (W/H ratio) in the group receiving B. longum APC1472 supplementation compared with the group receiving placebo.

On the other hand, there was a decrease in fasting blood glucose levels in participants receiving B. longum APC1472 supplementation. However, there was no change seen in insulin activity.

In healthy obese adults, B. longum APC1472 supplementation was also shown to be associated with increased active ghrelin and cortisol awakening responses. B. longum APC1472 treatment did not have a major impact on microbiota composition, as observed in the preclinical study.

The data gathered in this study indicates that dietary supplementation with B. longum APC1472 has the same beneficial influence on fasting blood glucose in both healthy but overweight or obese human individuals and a preclinical mouse model of obesity.

This spotlights the potential for B. longum APC1472 to be developed as a valuable supplement for decreasing specific markers of obesity.

Further studies are required to assess the metabolites and mechanisms through which B. longum APC1472 modulates host glucose homeostasis, with a key focus on the ghrelinergic system.

References

1. WHO. Obesity and overweight - key facts. 2018. Available from: https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight.
2. Tchernof A, Despres JP. Physiol Rev 2013;93(1):359–404.
3. Narayanaswami V, Dwoskin LP. Pharmacol Ther 2017;170:116–147.
4. Carmody RN, et al. Cell Host Microbe 2015;17:72-84
5. Sharma V, et al. Cell Reports 2018;24(12):3087-3098
6. David CF, et al. Nature 2014;505:559-563
7. Wu GD, Lewis JD. Clin Gastroenterol Hepatol. 2013;11(7):774-777.
8. Cani PD, et al. Nat Metab 2019.
9. Rosenbaum M, et al. Trends Endocrinol Metab 2015;26(9):493–501
10. Everard C, et al. Proc. Natl. Acad. Sci. USA 2013;110:9066-9071
11. Ridaura JJ, et al. Science 2013;341:12412146
12. Backhed F, et al. PNAS 2004;101(44):15718–15723
13. Torres-Fuentes H, et al. Lancet Gastroenterol Hepatol 2017.
14. Hibberd AA, et al. Benef Microb 2019;10(2):121–135.
15. Torres-Fuentes C, et al. FASEB J 2019. fj201901433R.
16. Schellekens H. et al. EBioMedicine 2020;103176

About Atlantia Clinical Trials

Atlantia Clinical Trials Ltd is a CRO that specializes in conducting studies in foods, beverages and supplements for companies world-wide that want to scientifically validate their functional ingredients to support an: EFSA (European Food Safety Authority) Health Claim; FDA (Food & Drug Administration) Structure Function Claim; or General Product Marketing Claim.

Atlantia works with world leading scientists (among the top cited 1% internationally, in the areas of digestive health and functional foods) at the: APC Microbiome Institute in University College Cork, Ireland; Teagasc, Moorepark, Ireland and recognized centers of excellence globally.

Atlantia runs and operates its own clinic sites and conducts all studies to ICH-GCP standard (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice). Its team includes physician experts in digestive health, mental health (psychological stress and cognition), cardiovascular health, sports performance, metabolic disease, bone health, immune health and healthy ageing. The clinical team also includes project managers, research nurses, nutritionists, certified sports trainers and lab researchers.

Atlantia manages all elements from protocol design, placebo manufacture, recruitment, and study execution, to sample and data analysis, statistics and report/dossier preparation to provide a service which is technically, scientifically and clinically superior.

The clinical studies cover a broad spectrum of functional food and beverage categories, such as dairy, cereal, probiotic, different protein forms, infant-specific foods, vitamins/minerals, plant or marine extracts and medical foods.

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