What is ffa in nutrition

Colors in the vertical bar at the right of the heatmap identify clusters I black and II gray. Tiles are colored based on serum FFA concentrations, red and blue indicating low or high levels, respectively.

B Biplot obtained in the cluster analysis of specific FFA serum levels. Red arrows represent the vectors showing the associations among the original variables entered and the outcome of the cluster analysis.

Numbers represent the final cluster assigned to each subject 1: cluster I, 2: cluster II. Boxes represent median and interquartile range, whereas whiskers represent minimum and maximum values.

Differences were assessed by Mann—Whitney U tests. Nutrient intakes were then compared between clusters in order to evaluate whether distinct daily intakes could account for the differences observed in FFA clusters. Interestingly, no differences in daily intakes were found Table 4 , hence supporting that additional factors other than demographic and nutritional parameters may underlie the differences found between FFA clusters.

Notably, important differences in intestinal microbial populations and fecal SCFA levels were observed between clusters Table 5. Cluster II was characterized by decreased levels of Akkermansia and increased Lactobacillus group counts as well as higher acetate, propionate and total fecal SCFA concentrations than cluster I. Moreover, increased total FFA [0.

Table 5. Intestinal microbial populations, fecal short-chain fatty acid SCFA , and serum cytokine levels according to free fatty acids FFA clusters. Finally, some statistical analyses performed independently within each cluster revealed particular interesting features for each group, thereby stressing the existence of important differences between groups.

Overall, our findings support the existence of homeostatic relationship between microbial populations, host lipid metabolism and inflammatory mediators. The strength of these associations was further analyzed by multiple logistic regression. This highlights the interplay between altered FFA profile, microbial populations and impaired host metabolism.

Moreover, additional observations reinforced the finding commented just above. Since our initial results point to a cross talk between host and microbial metabolism, we further deepen into this idea focusing on possible differential associations between microbial groups or SCFA with nutrient intakes. No associations were observed in those subjects free of metabolic alterations. In sum, these results support an association between microbial populations, nutritional factors, and impaired host metabolism.

Subjects exhibiting an altered FFA profile, which also display imbalanced Akkermansia and Lactobacillus populations, were more frequently associated with subclinical pathogenic metabolic states. Divergent patterns in the associations between dietary intakes with microbial populations and SCFA were also observed. Since the results commented just above suggest that altered microbial populations and their interactions with nutrient intakes may underlie impairment in the host metabolism and that SCFA can have relevance in such interactions, we included all these parameters microbial populations, SCFA, dietary intakes, age, gender, and BMI as independent variables in a multivariate regression analysis, FFA levels being selected as the dependent variable, after stratifying our populations by the clusters obtained in the previous analysis.

In summary, different factors were found to be associated with total FFA levels depending on the levels of Akkermansia. However, when Akkermansia abundance is low, factors other than the anthropometric characteristics as imbalanced microbial populations or SCFA production seem to impact the FFA pool. Despite the important research advances in recent years, the links between human metabolism and gut microbiota are far from being completely understood, especially in the field concerning the lipid metabolism.

The present study addresses a multilevel analysis of this scenario, by assessing different surrogate biomarkers of the lipid metabolism, in addition to some relevant intestinal microbial groups and SCFA production as well as inflammatory mediators; the study was performed in a sample of adult subjects from the general population in order to gain some insight into the relationship among these parameters and their potential impact on the human health. Our results revealed an association between the abundance of the intestinal microorganism Akkermansia and circulating FFA.

In addition, cluster analyses revealed that imbalanced intestinal microbial groups and levels of SCFA production may be related to an impaired FFA profile, pro-inflammatory and saturated fatty acids mainly hallmarking this group. Interestingly, individuals who exhibit these features were more likely to show metabolic alterations.

Therefore, the results herein presented provide valuable information on the gut microbiota-host metabolism axis and its involvement in human health. A major finding of our study was the association between Akkermansia and serum FFA levels. Akkermansia has been reported to participate in the maintenance of gut integrity and energy harvest by the host It has been confirmed that Akkermansia has a causative role in lowering body fat mass and in glucose homeostasis in mice models 35 , 36 , although evidence in humans is limited.

Our results demonstrate for the first time an association between Akkermansia and serum FFA in a cohort of human adults from the general population. Interestingly, we were able to cluster these healthy adults into two independent groups on the basis of serum individual FFA species, one of these groups showing an increased prevalence of subclinical metabolic alterations. In our study Akkermansia was negatively associated mainly with saturated FFA, in line with the differences that have been previously reported by other authors between lard-like and fish oil-enriched diets in the gut microbiota of mice 36 , Moreover, differences in Akkermansia abundance found in our study between FFA clusters were associated in turn with striking differences in total FFA levels.

In line with this hypothesis, below certain levels of Akkermansia abundance, gut barrier, and other functions developed by this microbe may become insufficient, thus promoting a shift from a healthy toward a pathologic-prone status. As previously commented, different parameters were found to be predictors of total FFA serum levels depending on the Akkermansia levels.

Therefore, low Akkermansia levels may render the host metabolism more sensitive to a number of factors which can lead to an imbalanced FFA profile and, potentially, altered metabolism, hence supporting this notion.

Akkermansia is known to reside within the mucus layer of the intestine, thus contributing to strengthen the intestinal wall Then, it is feasible that decreased Akkermansia levels may lead to a compromised barrier function and increased gut permeability, hence promoting metabolic endotoxemia, which has been related to the development of obesity and associated disorders 35 , Interestingly, we have found that decreased Akkermansia levels were associated with elevated IL-6 serum concentrations and impaired FFA profile, and the subpopulation with such profile exhibited a bias toward the enrichment in pro-inflammatory and saturated fatty acids, as well as an increased prevalence of metabolic disturbances, thus supporting those previous findings.

Therefore, these results suggest that Akkermansia may be linked to the inflammatory milieu by modulating the FFA profile in the host. Previous studies have revealed reduced levels of Akkermansia in patients suffering from inflammatory bowel disease or other metabolic impaired conditions 40 , 41 , although some controversy exist on the role of Akkermansia in these disorders. Interestingly, a recent study reported decreased counts of Akkermansia in pre-diabetic individuals 42 , suggesting an early involvement of this microorganism in metabolic disorders.

Thus, we decided to focus on subclinical metabolic features suggestive of an impaired metabolism , which can be detected in healthy subjects, in order to improve our knowledge on the potential role of Akkermansia as an early marker of impaired metabolic conditions in the general population. These metabolic features were related to an increased risk of metabolic complications in the long-term 43 — Based on this approach, it may be hypothesized that imbalanced microbial populations can underlie the subclinical stage of some metabolic conditions.

However, long-term studies are warranted. Importantly, we found an opposite behavioral pattern between Akkermansia and Lactobacillus groups, the latter being over-represented in subjects with impaired FFA profile and increased prevalence of metabolic traits.

Thus, these pieces of evidence point to a Lactobacillus within-group heterogeneity with relevance for the human health, as suggested by other authors 40 , Controversy observed in mice studies and clinical interventions in humans is also consistent with this idea.

A recent work shows opposite patterns upon mucin usage as substrate by Lactobacillus and Akkermansia 56 , thereby suggesting that trophic interactions may underlie, at least in part, these opposite trends of both microorganisms. Actually, a negative effect on Akkermansia levels in the gut upon administration of a probiotic mixture was observed when Lactobacillus , but not other probiotic bacteria, were added to the mixture This peptide specifically targets Gram-positive bacteria, thus potentially accounting for the opposite trends between Akkermansia and Lactobacillus groups.

In sum, it is feasible that Akkermansia may modulate the gut environment and some intestinal microbial populations through several mechanisms It has been reported that Akkermansia and Lactobacillus exhibited diverging trends in twins discordant for metabolic syndrome Our results herein presented are in line with these findings and suggest that the altered composition of the intestinal microbiota may be found in subclinical stages in healthy subjects.

A recent study in mice revealed that whereas the colonization by Akkermansia muciniphila shifted the intestinal mucosa gene expression profile toward gene pathways involved in immune tolerance and metabolic homeostasis, colonization by Lactobacillus plantarum resulted in an overexpression of genes involved in the metabolism of fatty acids, lipoprotein lipase being one of the most up-regulated genes An enhanced enzymatic activity of this enzyme may contribute to explain the striking increase in serum FFA found in association with increased Lactobacillus abundance in our study.

Actually, overexpression of lipoprotein lipase gene has been related to fatty acid accumulation and insulin resistance 60 , On the other hand, the balanced immune responses promoted upon Akkermansia colonization may also account for the increased IL-6 levels found in our study in subjects with diminished abundance of Akkermansia.

This is also in accordance with the positive effect on the induction of regulatory T cells reported in mice administered Akkermansia It must be noted that IL-6 can promote a number of pleiotropic functions other than triggering inflammation. However, since we have focused our analysis in subjects with no previous diagnosis of chronic or immune-mediated conditions, our approach allowed us to gain insight into the relationships between Akkermansia , IL-6 and low-grade inflammation in healthy states.

Nevertheless, these associations cannot be directly translated into pathological frameworks. Therefore, a study of the gut microbiota composition—IL-6 axis in disease stages remains to be elucidated.

Modulation by Akkermansia of genes involved in lipid metabolism seems to be mediated, at least in part, by the production of SCFA Imbalanced microbial populations can have an impact on SCFA production, which can elicit different responses in the host metabolism and immune system Interestingly, several authors have found increased SCFA in obesity and metabolic syndrome [reviewed in Ref.

The associations found in our study between acetate and IL-6 and that of the total SCFA with FFA serum levels strongly support the cross talk between gut microbiota, host metabolism and immune networks, highlighting a role for SCFA as important elements of this interplay.

The present study has a number of limitations that can be remarked. On the one hand, we have performed a targeted analysis of the gut microbial composition instead of a global profiling by 16S rRNA gene sequences analysis. As a consequence, whether a reduced diversity underlies the present findings cannot be concluded. Similarly, a number of selected FFA and the major SCFA species were chosen for the analysis, based on their outmost relevance in several biological processes.

In addition, the same concerns apply to the analysis of inflammatory mediators. Finally, a more precise characterization of dietary intakes may be needed to precisely account for the exact contribution of short-term nutrition to the FFA levels.

In conclusion, we reported an association between some intestinal microbial populations and the characteristics of the FFA profile in healthy middle-aged subject. Akkermansia and Lactobacillus groups seem to be connected to the health metabolic status of the host, the interplay with nutritional parameters playing a potential role Figure 4.

Finally, our findings provide some evidence on the role of SCFA as mediators of the cross talk in the gut microbiota-host lipid metabolism axis. Although our results point to a very early role of an altered microbial composition in the further development of metabolic disorders, prospective and long-term studies are needed to accurately address this possibility. Figure 4. Summary of the global findings of the present study and proposed hypothesis on their potential impact in human health.

A link between host lipid metabolism and gut microbiota with potential consequences for the human health is disclosed. On the one hand, above a certain value, Akkermansia levels seem to play a role in the maintenance of the serum free fatty acids FFA pool in healthy individuals. Decreased Akkermansia abundance in the gut microbiota, which seems to coincide in our study with increased Lactobacillus counts, is associated with an altered serum FFA profile, hallmarked by striking quantitative and qualitative differences in FFA as well as in IL-6 serum levels and intestinal short-chain fatty acid SCFA production.

These features, and their interaction with nutritional factors, were related to an increased prevalence of subclinical metabolic alterations. Thus, a link between dysbalanced microbial populations, host lipid FFA metabolism, and human health may be suggested, SCFA production playing an important role.

All the authors listed made substantial contributions to the design of the work, analysis, or interpretation of the results obtained; participated in the study design and data interpretation, reviewed the manuscript, and approved the final version; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

JR-C and NS performed most of the experimental procedures. SG was involved in the nutritional assessments, anthropometrical measurements, and collection of samples. JR-C and AS drafted the manuscript. The authors declared no potential competing financial interests concerning this study. Funders had no role in study conception, design, analysis of the results, or decision to publish. The authors acknowledge the excellent technical assistance of Ana M.

The authors also show their deepest gratitude to all the study volunteers. Induction of proinflammatory cytokines by long-chain saturated fatty acids in human macrophages. Atherosclerosis — Immunology — Free fatty acids: potential proinflammatory mediators in rheumatic diseases. Ann Rheum Dis — EPA and DHA exposure alters the inflammatory response but not the surface expression of Toll-like receptor 4 in macrophages. Lipids —9.

Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients. Each unit has primary, upper elemtary lessons and a demonstration plan. Primary lessons are written for high school students to deliver to students in grades K Upper elementary lessons are written for high school students to deliver to students in grades Demonstration plans are hands-on activities for all ages to get students involved and learn by doing.

They are set-up in an easy to follow bulleted format. Food and Agricultural Literacy Curriculum-Do your students know where their food comes from? Dieffenbacher and J. You currently have no access to view or download this content. Please log in with your institutional or personal account if you should have access to this content through either of these. Showing a limited preview of this publication:.

Eintragstyp Entry Type Definition Eintragssprache Entry Language Englisch English Abstract The intertwining of lipid nutrition with many other disciplines makes contributions from different directions imperative.

Beare-Rogers, A. Dieffenbacher, J. Holm Berlin, Boston: De Gruyter, Accessed