Absence of intestinal microbiota does not protect mice from diet-induced obesity

Abstract

The gut microbiota has been implicated in host nutrient absorption and energy homeostasis. We studied the influence of different diets on body composition in germ-free (GF) and conventional (CV) mice. GF and CV male adult C3H mice were fed ad libitum a semi-synthetic low-fat diet (LFD; carbohydrate -protein -fat ratio: 41:42:17; 19·8 kJ/g), a high-fat diet (HFD; 41:16:43; 21·4 kJ/g) or a commercial Western diet (WD; 41:19:41; 21·5 kJ/g). There was no difference in body weight gain between GF and CV mice on the LFD. On the HFD, GF mice gained more body weight and body fat than CV mice, and had lower energy expenditure. GF mice on the WD gained significantly less body fat than GF mice on the HFD. GF mice on both HFD and WD showed increased intestinal mRNA expression of fasting-induced adipose factor/angiopoietin-like protein 4 (Fiaf/Angptl4), but they showed no major changes in circulating Fiaf/Angptl4 compared with CV mice. The faecal microbiota composition of the CV mice differed between diets: the proportion of Firmicutes increased on both HFD and WD at the expense of the Bacteroidetes. This increase in the Firmicutes was mainly due to the proliferation of one family within this phylum: the Erysipelotrichaceae. We conclude that the absence of gut microbiota does not provide a general protection from diet-induced obesity, that intestinal production of Fiaf/Angptl4 does not play a causal role in gut microbiota-mediated effects on fat storage and that diet composition affects gut microbial composition to larger extent than previously thought.Obesity: Intestinal bacteria: High-fat diet: Angiopoietin-like protein 4: Energy metabolism

Gut microbiota and energy balance: role in obesity

“…In agreement with the higher leptin levels found in conventional mice compared with germ-free mice oxygen consumption, which reflects energy expenditure, was 27 % lower in the latter mice (29) . Such a difference in total energy expenditure monitored over 24 h was also observed in another mouse study, but interestingly this difference was only observed during night time, when the mice are active (34) . Do SCFA contribute to or rather prevent obesity development?…”

Impact of the Gut Microbiota on the Development of Obesity: Current Concepts

“…Using a resistin-like molecule-β (RELM β ) knockout mouse model that gains less weight than a wild-type mouse, it was shown that a high-fat diet is associated with a decrease in Bacteriodetes and an increase in both Firmicutes and Proteobacteria as previously reported; however, the change in microbiota occurred regardless of whether the mice were obese or not, suggesting that diet was the driving force behind this microbial change in abundance ( 19 ). Similarly, Fleissner et al ( 20 ) compared conventionally raised and germ-free mice fed either a low-fat, high-fat, or Western diet and found that the germ-free mice fed the high-fat diet gained more weight than the conventional mice, suggesting that diet is more important than gut microbes. Interestingly, they also reported an increase in Fiaf levels in the obese mice, contradicting the mechanistic fi ndings described previously ( 5 ).…”

“…Diet has recently been shown to strongly and rapidly infl uence the composition of the gut microbiota, raising the question of whether the diet independent of the obese phenotype is responsible for the changes in gut microbe composition ( 19,20 ). Using a resistin-like molecule-β (RELM β ) knockout mouse model that gains less weight than a wild-type mouse, it was shown that a high-fat diet is associated with a decrease in Bacteriodetes and an increase in both Firmicutes and Proteobacteria as previously reported; however, the change in microbiota occurred regardless of whether the mice were obese or not, suggesting that diet was the driving force behind this microbial change in abundance ( 19 ).…”

High-fat diet alters gut microbiota physiology in mice

“…150 kcal is associated with an increase of 20% in the sequence occurrence of Firmicutes and a corresponding decrease in the Bacteroidetes in humans, although the impact of high inter-individual differences in the percentage of energy lost in stools have been discussed (Heymsfield and Pietrobelli, 2011). Driven by the popularization of DNA sequencing-based approaches, many studies have described changes in gut bacterial diversity and composition after ingestion of high-energy diets (Cani et al, 2008;Turnbaugh et al, 2008;Fleissner et al, 2010). However, the consequences of such changes in bacterial diversity on the function of the ecosystem are still unclear.…”