*Only for reading and reference by medical professionals
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is right, is double and is intestinal flora !
In the biological research circle, everyone agrees that the intestinal flora has its own hot-searched constitution, and it is tied to hot topics such as metabolism and homeostasis.
As far as host metabolic homeostasis is concerned, it has to be said that our path has been narrow before - most studies on intestinal flora have focused on the large intestine or feces [1-2]. However, other areas of the intestine, especially the ileum, which has unique digestive and absorption functions and microbial composition, also play a crucial role in regulating the intestinal microenvironment, physiological metabolism, and immune homeostasis [3- 4].
No, Amir Zarrinpar’s team at the University of California, USA, has a keen eye and conducted a systematic study on the impact of ileal microbiota and its circadian rhythm on host metabolic health. They published important results in the journal Cell Reports, revealing The mechanism by which diet and eating time affects the composition of the ileal microbiota and the circadian rhythm of the transcriptome in mice has been studied [5].
This study points out that Diet-induced obesity (DIO) disrupts the circadian rhythm of the ileal microbiota composition and transcriptome, and time-restricted feeding (TRF) has a corrective effect on this disrupted rhythm , and can increase Glucagon-like peptide-1 (GLP-1, stimulates insulin secretion, can reduce food intake through central appetite suppression, thereby achieving hypoglycemic and weight loss effects) release, restore ileal bile acid pool and farnesol X receptor (FXR) signaling . These findings provide substantial evidence for the benefits of TRF on host metabolic health.
Effects of different diets and feeding patterns on the composition and rhythmic oscillations of ileal microbiota
TRF is a type of feeding pattern that limits the feeding time to 8-10 hours during the active period of mice (under dark conditions), which is very beneficial to the metabolic health of the host. There are benefits. It is reported that TRF can reduce obesity and inflammation, improve glucose tolerance and cholesterol homeostasis, and can also reverse the existing metabolic syndrome [6-7].
However, the mechanism of TRF's beneficial effects on host metabolism has never been elucidated. However, since we want to explore the impact of diet on metabolic health, we cannot skip the step of gut microbiota.
Previous research evidence shows that the circadian rhythm of the intestinal microbiota and its secondary metabolites regulates the peripheral clock and the rhythmic expression of hepatointestinal metabolism regulators (maintains glucose , cholesterol , fatty acid homeostasis and host metabolism Health) are necessary [8].
But the question is, can dietary changes in gut microbial community dynamics affect host metabolism through circadian rhythms?
Based on the above information, the Zarrinpar team designed three feeding models: normal diet group (NA), free high-fat diet group (FA) and time-limited high-fat diet group (FT), and collected data from each group at different time points every day Ileal samples from mice to study the effects of diet and feeding time on circadian rhythms of the ileal microbiota.
Schematic diagram of research design and sample collection
The results showed that high-fat diet reduced the α- diversity and β-diversity of the ileal microbiota; the difference in the composition of the ileal microbiota of mice in the FA and FT groups was small. It shows that dietary type can affect the composition of ileal microbiota more than eating pattern.
Regarding the circadian rhythm of the ileal microbiota, the researchers found that in the ileum of mice in the FA group, the abundance of bacterial flora that maintained rhythmic oscillations was less than half that of the mice in the NA group, while the mice in the FT group showed the same Similar levels of cyclic fluctuations in were observed in mice in the NA group, which preliminarily indicates that TRF can improve the circadian rhythm of ileal microbiota that is disrupted by high-fat diet.
Periodically changing amplicon sequence variations and total proportions in mouse ileal microbiota under different feeding modes
Further studies found that lactic acid bacteria were rhythmic only under high-fat feeding conditions, and their abundance increased during mouse activity (dark phase) was significantly reduced; although the abundance of Lactococcus in the light phase was not much different between the two high-fat feeding conditions, only the FT group showed rhythmicity, and Staphylococcus aureus and Streptococcus were also evident in the FT rhythmicity.
It can be seen that TRF can indeed restore or maintain the circadian rhythm of the ileal microbiota.
relative abundance of specific bacteria at the genus level , "@" indicates the rhythmicity of intestinal bacteria under specific feeding conditions
Research reports that the circadian rhythm of the intestinal microbiota can affect the liver transcriptome [9], a brief introduction , is the ileal transcriptome also affected by this?
results showed that periodic transcripts were significantly reduced in FA compared with NA and disrupted their circadian rhythm by inducing a phase shift of periodic genes toward the light phase.
In contrast, FT not only maintained similar transcript levels to NA, but also partially restored the phase of transcripts disrupted by high-fat diet, indicating that ileal microbiota periodic dynamics are related to TRF's maintenance of the host peripheral clock circadian rhythm .
Phase distribution of periodic genes
In addition, FA disrupted many circadian rhythm genes in the ileum, including Rev-erb, Per3, Clock, Bmal1, Cry1, Cry2, Ppara, and Nfil3, while these genes did not change much in FT.
It can be speculated that the improvement of obesity and metabolic disorders in mice by TRF may be related to its maintenance of ileal circadian rhythm, the cycle phase of circadian clock genes and intestinal dynamics.
Circadian Rhythmic Gene Expression Dual Figure
So, how does TRF affect the intestinal metabolism signaling pathway by maintaining the circadian rhythm of the ileal microbiota?
Researchers found that under FA conditions, the expression levels of the proglucagon gene Gcg (GLP-1 precursor) and the gene encoding GLP-1 Dpp4 were significantly reduced and the circadian rhythm was lost, while TRF not only restored The expression levels of Gcg and Dpp4 can also maintain the circadian rhythm of both.
Effects of different feeding patterns on GLP-1 signaling pathway transduction
In addition, the signal transduction of cholesterol homeostasis, bile acid pools, and bile acid transport and reabsorption disrupted by high-fat diet can also be reversed by TRF.
Overall, this study fully clarifies the important role of ileal microbiota composition and transcriptome circadian rhythm in host metabolic health, provides scientific basis for the metabolic benefits of time-restricted feeding at the animal level, and also opens up the ileum. The curtain rises on the stage of intestinal flora research!
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Reference:
1. Thaiss CA, Zeevi D, Levy M, et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014;159 (3):514-529.
2. Thaiss CA, Levy M, Korem T, et al. Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. Cell. 2016;167(6):1495-1510.e12.
3. Gu S, Chen D, Zhang JN, et al. Bacterial community mapping of the mouse gastrointestinal tract. PLoS One. 2013;8(10):e74957.
4. Martinez-Guryn K, Leone V, Chang EB. Regional Diversity of the Gastrointestinal Microbiome. Cell Host Microbe. 2019;26(3):314-324.
5. Dantas Machado AC, Brown SD, Lingaraju A, et al. Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome. Cell Rep. 2022;40 (1):111008.
6. Chaix A, Lin T, Le HD, Chang MW, Panda S. Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock. Cell Metab. 2019;29(2):303 -319.e4.
7. Chaix A, Deota S, Bhardwaj R, Lin T, Panda S. Sex- and age-dependent outcomes of 9-hour time-restricted feeding of a Western high-fat high-sucrose diet in C57BL/ 6J mice. Cell Rep. 2021;36(7):109543.
8. Bishehsari F, Voigt RM, Keshavarzian A. Circadian rhythms and the gut microbiota: from the metabolic syndrome to cancer. Nat Rev Endocrinol. 2020;16(12) :731-739.
9. Manella G, Sabath E, Aviram R, et al. The liver-clock coordinates rhythmicity of peripheral tissues in response to feeding. Nat Metab. 2021;3(6):829-842.
Author of this article丨Xia Tian
editor in charge 丨 Dai Siyu
