A link between fasting and the microbiome?

Alekha Akkapeddi

Research shows that although it does matter what we eat, it is also important WHEN we eat.

Why?

There are benefits to eating earlier in the day because our internal rhythms are highly in sync with Earth’s rhythms.

What are circadian rhythms and why are they important?

The human body operates differently during the day vs at night. We have a central clock located in the suprachiasmatic nucleus(SCN) in the brain along with peripheral clocks located in the heart, liver, kidneys, lungs, intestines, skin, lymphocytes, esophagus, spleen, thymus, adrenal gland, prostate, and olfactory bulb. Through an array of complex pathways, these clocks are responsible for regulating sleep, body temperature, hormonal secretion, memory consolidation, immunity, appetite and other bodily functions(1). These clocks are entrained by cues called “zeitgebers” and include light, eating and exercise. The SCN is mostly entrained by light, but other peripheral clocks are powerfully influenced by food intake. 

Common diseases found society today such as diabetes, heart disease, stroke, reproductive disorders, mood disorders, learning deficits and others all occur when these clock mechanisms are dysregulated. Shift work, jetlag, light from our devices, late night eating patterns, and gene mutations can all disrupt circadian rhythms and cause circadian misalignment(CM)(2). 

Another interesting concept is that circadian rhythms are impacted based on seasonal change in daylength(3). The basis of this is that these circadian phase shifts disrupt hormone production such as melatonin and subsequently leads to stress hormone dysfunction(4). It is imperative to align our sleep and eating behaviors with the 24-hr solar light/dark cycle as our endogenous rhythms are tightly linked with the Earth’s.

• Fasting and circadian rhythms

  Fasting and time restricted eating are beneficial because timely food intake plays a role in how optimally our metabolic pathways are being used.

• Time Restricted Eating

  You’ve likely heard of the 16:8 approach when discussing intermittent fasting, as this is one of the most common approaches. Time restricted eating(TRE) is when an individual consumes their food intake between a time window (usually eating between 6-10 hour fasting for 14-18 hours). The benefits of TRE are endless and include reduction in body weight, reduced cardiometabolic disease risk, improved gut health, autophagy, decreased inflammation, among many others(3).
  
  Eating all day and late night eating have been associated with higher postprandial glucose levels compared to daytime levels. This is based on the premise that there are varying levels of clock gene expression based on the time of day. This is tightly linked with glucose metabolism, fatty acid oxidation, bile salt signaling, immune response and others.
  
  Insulin release also has a circadian component where it is higher in the first part of the day. One possible mechanism is that melatonin release during the nighttime may hamper insulin release(3).
  
  Evolutionarily, these mechanisms likely have developed since human beings did not have constant access to food. This adaptation to food scarcity switched metabolism from utilization of liver-derived glucose to a ketogenic state where adipose cell-derived fatty acids and ketones were used as cellular fuels to sustain cognitive performance and physical endurance(5).

• Eating behaviors in winter… TRE as an
  intervention?

  Our evolution favors increasing our fat stores during the winter(presumably due to not having the same access to food as during summer months) as many other organisms do. A review(6) has shown that hunger hormones(ghrelin) have a seasonality difference. Stress hormones are also shown to be elevated in winter which has an impact on hunger. Depending on the circumstance, an individual may consume more when stress hormones are elevated. Thus, time restricted eating may be used as a mitigation strategy to prevent this excess consumption of calories. Since there is also less daylight during the winter, eating should be limited to these sunlight hours.

Connection between fasting and gut microbiome

• Gut Microbiome their connection with
  rhythmicity

  The gut is colonized by diverse bacteria that play a role in a variety of physiological functions. They contribute to our health by breaking down resistant starches, alter bile acid signaling, synthesize amino acids, as well as other metabolic tasks. Gut microflora composition is attributed mainly to nutritional factors. There are notable differences in microbiome that are observed in obese vs lean populations. Specifically, obesity is associated with a reduction in bacteria from the Bacteroidetes phylum and an increase in bacteria from the Firmicutes phylum(3).
  
  Similar to other organisms, the gut microbiome goes through cyclical fluctuations in expression through the day which is important for our metabolism and health. The two main phyla of the gut microbiome— Bacteriodies and Firmicutes display diurnal rhythms. Studies show that Bacteriodies peaks near the end of the fasting phase and Firmicutes peaks during the end of the feeding phase. Unfortunately, it has been studied that obesity induced by diet in mice dysregulates these rhythms of the microflora(8)

• Fasting and the gut microbiome

  There is data to support (8,9) that timing of meals also plays a role in microbiome composition. These studies show that fasting can restore these normal rhythms, to a degree, despite eating a high fat diet. By having these normal rhythms be restored, the gut microflora can express its most appropriate time-dependent diversity which will best support our metabolic pathways.
  
  Additionally, time restricted feeding(TRF) decreases obesity causing bacteria and increases obesity protective bacteria. TRF significantly reduces the abundance of Lactococcus species during the rest phase of mice in research studies. Similarly mice that were fasting also had lower levels of Lactobacillus. TRF mice also had relatively high levels of Oscillobacter and Ruminococcaceae species that are protective against obesity and nonalcoholic fatty liver disease.
  
  While it is important to eat a well-balanced diet to promote health and microbiome diversity, timing of meals cannot be overlooked. It is better to eat earlier in the day as this is the time when our internal clocks are best in sync with the external clock.

References:

1. Reddy S, Reddy V, Sharma S. Physiology, Circadian Rhythm. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519507/

2. https://www.nhlbi.nih.gov/health/circadian-rhythm-disorders

3. Emily N C Manoogian, Lisa S Chow, Pam R Taub, Blandine Laferrère, Satchidananda Panda, Time-restricted Eating for the Prevention and Management of Metabolic Diseases, Endocrine Reviews, Volume 43, Issue 2, April 2022, Pages 405–436, https://doi.org/10.1210/endrev/bnab027

4. Lewy AJ, Lefler BJ, Emens JS, Bauer VK. The circadian basis of winter depression. Proc Natl Acad Sci U S A. 2006 May 9;103(19):7414-9. doi: 10.1073/pnas.0602425103. Epub 2006 Apr 28. PMID: 16648247; PMCID: PMC1450113.

5. Mattson MP. An Evolutionary Perspective on Why Food Overconsumption Impairs Cognition. Trends Cogn Sci. 2019 Mar;23(3):200-212. doi: 10.1016/j.tics.2019.01.003. Epub 2019 Jan 19. PMID: 30670325; PMCID: PMC6412136

6. Cahill S, Tuplin E, Holahan MR. Circannual changes in stress and feeding hormones and their effect on food-seeking behaviors. Front Neurosci. 2013 Aug 7;7:140. doi: 10.3389/fnins.2013.00140. PMID: 23966906; PMCID: PMC3735984.

7. https://www.everydayhealth.com/diet-nutrition/why-do-we-eat-more-in-winter.aspx

8. Zarrinpar A, Chaix A, Yooseph S, Panda S. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab. 2014 Dec 2;20(6):1006-17. doi: 10.1016/j.cmet.2014.11.008. PMID: 25470548; PMCID: PMC4255146.

9. Dantas Machado AC, Brown SD, Lingaraju A, Sivaganesh V, Martino C, Chaix A, Zhao P, Pinto AFM, Chang MW, Richter RA, Saghatelian A, Saltiel AR, Knight R, Panda S, Zarrinpar A. Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome. Cell Rep. 2022 Jul 5;40(1):111008. doi: 10.1016/j.celrep.2022.111008. PMID: 35793637; PMCID: PMC9296000.