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High-Fat Diets Linked With Changes in Gut
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Significant changes in gut microbiota, fecal metabolic profiles with higher fat diets
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Feb 22 2019
Higher fat diets were linked with changes in gut microbiota, as well as adverse effects on certain biomarkers in young adults, Chinese researchers found.
Compared to a lower-fat diet, a higher-fat diet was associated with changes in gut microbiota, fecal metabolomic profiles, and proinflammatory factors for healthy young adults, reported Duo Li, MB, PhD, of Qingdao University in Qingdao, China, and colleagues, in the journal Gut.
Calling the study "interesting," Purna C. Kashyap, MBBS, of the Mayo Clinic in Rochester, Minnesota, told MedPage Today that the change in Firmicutes to Bacteroides ratio described in the study is consistent with prior findings. Kashyap was not involved with the research.
"The study also found intriguing associations between the dietary intervention and bacterial metabolites, especially the indole compounds, but it still remains to be determined if these metabolites are responsible for the metabolic improvement in patients or simply an adaptation by microbes to changes in diet," Kashyap said.
Kashyap added that as in previous findings from smaller dietary studies, the magnitude of change in the human microbiome following dietary intervention is much lower than that observed in mouse studies.
In terms of promoting circulating proinflammatory factors, the higher-fat diet was tied to increased plasma high-sensitivity C-reactive protein and thromboxane B2 versus its lower-fat counterpart, while leukotriene B4 and prostaglandin E2 in the lower-fat diet decreased.
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Original article
Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial
Conclusion
In summary, compared with a lower-fat diet, long-term consumption of a higher-fat diet appears to be undesirable owing to changes in gut microbiota, faecal metabolomic profiles and proinflammatory factors for healthy young adults whose diet is in transition from the traditionally consumed lower fat, higher carbohydrate diet to one characterised by an appreciably higher fat content. These findings might also have relevance in developed countries in which fat intake is already high.
Introduction
The parallel increases in dietary carbohydrate and the prevalence of obesity and type 2 diabetes (T2D) in the United States and some other Western countries have led to the suggestion that this dietary change, resulting from an increase in carbohydrate consumption and a reduction in total fat intake, might be a determinant of cardiometabolic disorders.1-3 By contrast in China, the nutritional transition from the traditional low-fat, high-carbohydrate diet to a diet relatively higher in fat and lower in carbohydrate has been associated with a dramatic increase in the risk of obesity, T2D and cardiovascular diseases in the past 30 years.4 5 We have previously shown in a randomised controlled-feeding trial that among healthy young adults, a lower-fat, higher-carbohydrate diet is likely to be associated with a lower risk of excessive weight gain and increase in waist circumference and a more favourable lipid profile than a higher-fat, lower-carbohydrate diet.6
There has been interest in the role of gut microbiota in the development of obesity and cardiometabolic diseases.7Rodent studies have suggested that the high-fat Western-type diet has a strong effect on the genetic composition and metabolic activity of gut microbiota.8 9 Evidence has shown that in humans gut microbiota diversity and richness are reduced when comparing such high-fat diets with more traditional diets with relatively higher proportions of carbohydrate.10 11 Such diet-induced 'dysbiosis' in gut-associated microbial communities has been postulated as a major trigger of metabolic impairments associated with obesity.12 Much of the relevant existing literature on humans is based on observational studies and the relatively few short-term dietary intervention trials suggest that the effect of dietary change might be relatively modest.13-16 No information is available relating to healthy young people or to populations whose diet is in transition from that traditionally consumed to one associated with a high risk of cardiometabolic disease.
Thus in a 6-month randomised controlled-feeding trial among healthy young adults, we compared a number of attributes of gut microbiota and faecal metabolomic profiles as well as markers of inflammation for diets of differing proportions of fat and carbohydrate.
Discussion
We believe that the present randomised, controlled-feeding trial, is the first study to investigate the effect of different proportions of dietary fat intake on gut microbiota, faecal metabolomic profiles and plasma inflammatory factors in healthy young adults drawn from a population whose diet is in a state of transition. The findings of our study suggest that although the three diets did not induce major changes of the global gut microbiota composition, the higher-fat diet had overall unfavourable effects on several important biomarkers, while the lower-fat diet with a macronutrient distribution corresponding to those consumed in China until some 30 years ago, appeared to have beneficial effects.
Numerous rodent studies have reported that a high-fat diet might appreciably unbalance the gut microbiota composition.21 However, the effect of diet on the human gut is complex given the considerable individual variation in the response of the gut microbiota to dietary intervention.22 23 Our findings are in keeping with previous studies, which indicate that the overall structure of gut microbiota is principally influenced by long-term dietary intake.10 13-15 23 24 Short-term effects have mainly been reported in studies with small sample size,25 26 and characterised by extreme and unrealistic dietary intakes25 or when the subjects studied were at high cardiometabolic risk.27-29A 10-day clinical trial with nine participants reported that the composition and function of the microbiota were rapidly changed when carbohydrates were eliminated from the diet, a dietary intervention which is neither sustainable nor desirable in the long term.25 In much more moderate dietary interventions that can be sustained in humans, high interindividual variations among subjects might have masked minor changes in distinct taxonomic groups.30 It has been reported that diet might have a greater influence on the metabolic activity of the gut microbiota than on its taxonomic composition.16 In accordance with this proposition, in our study diets differing in dietary fat content provoked a marked shift of faecal concentrations of metabolites produced by the gut microbiota.
We found Blautia and Faecalibacterium, genera known to contain butyrate-producing bacteria, were increased in the lower-fat diet group. Blautia is a group of bacteria containing various acetate and butyrate producers and reported to have a lower relative abundance in patients with T2D than in healthy controls.31 32 Faecalibacterium contains anti-inflammatory and functionally important bacteria.33 Higher abundance of F. prausnitzii was associated with a reduction of systematic low-grade inflammation among obese subjects receiving bariatric surgery.34 Many previous studies have reported the benefits of dietary fibre on gut microbiota.35 In our study, the amount of carbohydrate was highest in the lower-fat diet group, mainly from white rice and wheat flour (bread). The proportion of resistant starch has been reported to be 3% in white rice and 2% in bread.36 37 Given that dietary fibre intake did not differ among the three groups, it is possible that the favourable effects of the lower-fat diet in our study might be due to the increased amount of resistant starch which can, like dietary fibre, be fermented by the gut microbiota, with associated health benefits.
In contrast, the abundance of Faecalibacterium was decreased and Bacteroides and Alistipes were increased after the higher-fat diet intervention. Among the Chinese population, Bacteroides and Alistipes were found to be more abundant in patients with T2D than in subjects with normal glucose metabolism.38 These changes at genus level indicated that dietary fat content had a selective effect on the human gut microbiota, which might have clinical significance among healthy young adults. The higher-fat diet induced a reduction in faecal butyrate acid and SCFAs as opposed to the lower-fat diet group. This is probably due to the reduction in dietary carbohydrate intake.39 It has been suggested that the benefits of a 'healthy diet' are mediated via the anti-inflammatory effects of SCFAs and other bioactive compounds produced by the gut microbiota.40 Several observations in our study pointed towards an effect of gut microbiota-mediated proinflammatory factors. Among the individual genera which responded to the dietary intervention, the abundance of Faecalibacterium was directly related to the concentration of butyric acid, as suggested by the positive association between changes in butyrate concentration and the abundance of Faecalibacterium. A study using faecal microbiota transplantation from lean donors to insulin-resistant patients with metabolic syndrome demonstrated that faeces from lean subjects were associated with enhanced numbers of butyrate-producing bacteria and increased insulin sensitivity.41 In contrast, a significant reduction of dietary carbohydrates in omnivores led to much lower levels of faecal SCFAs and decreased bacterial numbers.39 The protective role of SCFAs against different types of disease is well documented; in particular, butyric acid can serve as the energy substrate for epithelial cells of the gut and confer anti-inflammatory effects.42 The reduction in SCFAs induced by the higher-fat diet was presumably detrimental for metabolic health.
In addition to the reduction of SCFAs, the higher-fat diet induced significant alterations in long-chain fatty acids metabolism. The faecal concentrations of palmitic acid (C16:0) and stearic acid (C18:0) were significantly increased in the higher-fat group. Palmitic acid and stearic acid, the main saturated fatty acids, in food and tissues, have been considered to stimulate inflammatory signalling in macrophages, adipocytes, myocytes, hepatocytes, etc.43Epidemiological studies showed that plasma phospholipid palmitic acid and stearic acid were positively associated with the incidence of T2D and cardiovascular diseases.44 Notably, the predicted lipopolysaccharide biosynthesis and arachidonic acid metabolism pathways were also increased in response to the higher-fat diet.
Lipopolysaccharide is known to induce the release of arachidonic acid and its inflammation-involving metabolites, such as prostaglandins, thromboxane and leukotrienes.45 It should be noted that the intake of polyunsaturated fatty acids (PUFAs) was relatively high in the higher-fat diet group (24% of total energy) owing to exclusive use of soybean oil, which is rich in n-6 PUFA. A higher intake of n-6 PUFA has been reported to have proinflammatory effects.46 Consistent with the predicted pathway analysis, we found the faecal concentration of arachidonic acid (the precursor of proinflammatory compounds like PGE2, TXB2 and LTB4) was indeed increased in the higher-fat group. The positive association between changes in faecal arachidonic acid concentration and the changes in plasma levels of inflammatory makers—namely, PGE2 and TXB2, suggested a potential mechanism through which the amount of dietary fat consumption affects inflammation via gut microbiota.
Interestingly, although the same amount and quality of protein was provided in each diet group, we found that the lower-fat diet group induced a significantly alteration in the amino acids metabolism, indicating enhanced protein degradation by the gut microbiota. The results reinforced the view that luminal substrate availability is also an important variable for fixing bacterial metabolite concentration.16 The lower-fat diet group induced reduction of faecal concentrations of indole and p-cresol, the host microbiota cometabolites derived from amino acids, while the higher-fat diet led to an increase in indole concentration. Indole is the precursor of indoxyl sulfate, which has been linked with hypertension and cardiovascular disease in people with chronic kidney disease.47 Likewise, p-cresol, the precursor of p-cresol sulfate, has been shown to act as an inhibitor of colonocyte oxygen consumption and as a genotoxic agent in vitro.48 Production rates of these potentially toxic compounds are found to be markedly lower in vegetarians than in people consuming an unrestricted diet.49 It has also been reported that bacterial diversity is higher among populations adopting a lower-fat diet like a vegetarian diet and can be modified through dietary intervention in obese subjects.50 It should be noted that the microbial α-diversity (indicated by the Shannon index) was increased in the lower-fat group compared with the higher-fat diet group. Increased diversity has been associated with improved health in the elderly, and reduction of gut microbial diversity has been linked to increased risk of gastrointestinal diseases and proinflammatory characteristics.14 51 Thus, in addition to increased SCFAs, our data suggest that the lower-fat diet can decrease the luminal concentration of these deleterious compounds while increasing the gut microbial α-diversity.
Correlation analysis allowed us to identify several new bacterial genera potentially implicated in the host metabolic health. We observed negative associations of Blautia abundance with serum concentration of TC, LDL-C and non-HDL-C, whereas the opposite was seen for Bacteroides, a genus that we found to be increased after higher-fat consumption. A previous clinical trial reported that T2D and hyperlipidaemia patients were ameliorated by metformin and a herbal formula with increased abundance of Bautia, which was correlated significantly with the improvement in circulating glucose and lipids.52 Also, in line with a clinical trial in which Blautia was found to be negatively associated with TC and non-HDL-C, we observed similar negative associations between Blautia and blood lipid profiles.53 The enrichment of Blautia in the lower-fat group suggested that the diet-induced change in gut microbiota might be related to the host lipid homoeostasis in healthy young adults and possibly, be a future target for the management of subjects with cardiometabolic diseases.
A limitation of this study was that faecal sampling was carried out only at baseline and at the end of the trial. A more complete picture of changes in gut microbiota would have been possible with more frequent sampling. In addition, all three groups lost weight and weight loss differed among groups after dietary intervention. Whether weight loss led to the changes in gut microbiota and faecal metabolomics or vice versa needs to be studied further. Another limitation relates to the generalisability of our study since our subjects were healthy young non-obese adults; the results might not apply to people at high risk of cardiometabolic diseases. The strengths of this study included the controlled-feeding design, the large sample size and the relatively long intervention period. In contrast to previous studies, we applied 16S rRNA amplicon profiling and quantitatively targeted bacterial metabolomics, which allowed us to understand both gut microbiota response and bacterial metabolites to gain more information about host-gut microbiota metabolic interactions in response to dietary fat content.
Conclusion
In summary, compared with a lower-fat diet, long-term consumption of a higher-fat diet appears to be undesirable owing to changes in gut microbiota, faecal metabolomic profiles and proinflammatory factors for healthy young adults whose diet is in transition from the traditionally consumed lower fat, higher carbohydrate diet to one characterised by an appreciably higher fat content. These findings might also have relevance in developed countries in which fat intake is already high.
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