Preliminary findings linking intestine microbiota and weight problems: insights from animal fashions
Although weight problems is the results of a long-term imbalance between vitality consumption and vitality expenditure, life-style interventions aimed toward restoring that imbalance don’t work for everyone. In recent times, rising proof has linked weight problems to the intestine microbiota.
Preliminary findings in rats twenty years in the past confirmed that adjustments within the intestine microbiota attributable to fermentable fiber comparable to inulin-type fructans (e.g., inulin or oligofructose) lowered physique weight and adipose mass in rats by involving intestine peptides that regulate urge for food. Extra findings confirmed that slim germ-free mice colonized with a standard intestine microbiota gained extra physique fats by 60% and elevated their insulin resistance, though they lowered their meals consumption. When utilizing a humanized mouse mannequin, researchers confirmed that mice receiving the microbiota from overweight human donors gained extra weight as in comparison with their counterparts receiving the microbiota from a genetically-identical twin pair however which was lean. Nevertheless, the germ-free mannequin extensively utilized in elucidating the causal position of the microbiota throughout weight problems additionally has its caveats, because the housing circumstances of mice can result in contradictory leads to the context of weight problems (see right here and right here).
The issue of translating mouse outcomes into the human context
When information throughout totally different human research had been analyzed, the connection between weight problems and intestine microbiota composition was much less robust. Whereas intestine microbiota composition is a vital contributor of weight acquire in mouse fashions, it is probably not crucial issue driving human weight adjustments. This may be defined by the truth that various factors that ought to be thought of as confounding variables in human microbiome research (e.g., social setting and social stress, a number of dietary components, particular medication and bariatric surgical procedure) can have an effect on each the composition and variety of the intestine microbiota. Up to now, there is no such thing as a clear hallmark of weight problems based mostly on the intestine microbiota composition and the so referred to as “Firmicutes/Bacteroidetes ratio” is without doubt one of the instance that ought to now not be used.
Weight-loss interventions that have an effect on the intestine microbiota
Essentially the most extensively studied weight-loss interventions that form the intestine microbiota and host hormones embrace dietary patterns (e.g., Mediterranean weight-reduction plan, fiber-enriched weight-reduction plan and ketogenic weight-reduction plan), fasting, bodily exercise, some medicines (e.g., anti-obesity medication comparable to Orlistat and glucose reducing medication comparable to Metformin), fecal microbiota transplantation and bariatric surgical procedure.
Food plan is the intervention with the strongest impression on the intestine microbiota and a Mediterranean weight-reduction plan wealthy in fiber is the dietary sample supported by human information with probably the most proof to help its use for enhancing cardiometabolic well being. In distinction, the advantages of the ketogenic weight-reduction plan for selling weight reduction that come largely from mice information should not conclusive. Whereas intermittent fasting is one other in style weight-reduction plan used for reducing weight, obtainable research are restricted and more often than not of quick length, which limits making normal suggestions for weight reduction. Subsequently, the very best methodology for reducing weight might be based mostly on personalizing dietary recommendation with the assistance of a registered dietitian, whereas the science stays restricted on using the outcomes of what sort of microbes reside in our intestine as technique of serving to with reducing weight.
Concentrating on the human intestine microbiota with particular micro organism linked to helpful results within the context of weight problems comparable to on insulin resistance and pre-diabetes can be one other possible possibility. The case of Akkermansia muciniphila is a key instance. This bacterium is a standard inhabitant of the human intestine. It has been proven that each reside micro organism and pasteurized A. muciniphila (i.e., heat-inactivated type) could enhance insulin sensitivity, whole ldl cholesterol and liver dysfunction and reduce blood inflammatory markers when supplemented for 3 months to individuals who met the factors for metabolic syndrome. Though, no particular results on physique weight had been noticed on this research.
As an alternative of administering a couple of micro organism in low doses in type of a probiotic, consortia of micro organism additionally provide a possible new remedy for weight administration. Nevertheless, whereas a couple of randomized placebo-controlled research have explored the administration of fecal microbiota transplants in sufferers with weight problems and metabolic syndrome, their efficacy is proscribed and depends largely not solely on donors’ weight-reduction plan and intestine microbiota composition, however on the recipient intestine microbiota.
The mechanisms by which microbiota-targeted interventions impression host metabolism contain many potential components such because the manufacturing of short-chain fatty acids, endocannabinoids, tryptophan metabolites and bile acids. For example, each butyrate and propionate stimulate the secretion of intestine peptides comparable to glucagon-like peptide 1 (GLP1), peptide tyrosine tyrosine (PYY) and GLP2. These results can contribute to cut back meals consumption, enhance glucose metabolism, keep irritation at bay and hold anaerobic circumstances within the intestine lumen. These adjustments may stop the metabolic endotoxemia that accompanies weight problems by stopping lipopolysaccharide (LPS) leakage into the bloodstream. Strikingly, particular microbial profiles have been discovered within the liver, adipose tissue and plasma in individuals with morbid weight problems and diabetes, whereas their relevance to host metabolism stays to be seen.
Take-home messages
To sum up, whereas the primary remedy for cardiometabolic issues is a nutritious diet and ample train, intestine microbiota-related interventions have introduced new hope regardless of being a brand new area of analysis. One problem that ought to be overcome is to maneuver away from easy associations between shifts within the intestine microbiota on the taxonomic degree and the options of weight problems. As an alternative, additionally exploring the metabolic capability of the intestinal microbiota and metabolites produced appears to be extra related when it comes to well being outcomes. Attempting to keep away from the classification of intestine microorganisms as “good friend” or “foe” may assist in advancing the sphere, as can measuring confounders that may impression the consequences of the intestine microbiota on the host metabolism.
Reference:
Van Hul M, Cani PD. The intestine microbiota in weight problems and weight administration: microbes as associates or foe? Nat Rev Endocrinol. 2023; 19(5):258-71. doi: 10.1038/s41574-022-00794-0.