INTERMITTENT FASTING

and THE MICROBIOME

Short takes

• Limiting your eating to specific hours changes your gut bacteria for the better;

• Time-restricted eating (TRE) changes how your body works by affecting your internal clock, metabolism, immune system, and the production of important biological compounds;

• Early-day eating (7 AM to 5 PM may be ideal) appears to work better than late-day eating - it helps control insulin levels throughout the day and may prevent diabetes;

• Longer fasting windows lead to more weight loss; benefits of shorter fasting intervals focus on ease of implementation;

• The best of both words may be the 13:11 diet, 13 hours of overnight fasting, and 11 hours of eating during the day. 14:10 is likely also great, and 12:12 is minimalist but probably still beneficial;

• Beyond just weight loss, TRE shows promise for improving multiple health conditions including heart health, eye health (especially in diabetes), and possibly stroke protection.

Favorite finds

• Apps can help with intermittent fasting. Here’s one review: https://www.goodhousekeeping.com/health-products/g34618367/best-apps-intermittent-fasting/

• A simple tip: set an alarm 1 hour before the end of your eating window and consider a snack at that time, so you don’t get hungry closer to bedtime;

• Keep bedtime regular; if you stay up too late you could get hungry again;

• Breast cancer survivors who fast 13 hours most nights have a lower recurrence rate than those who don’t, suggesting that overnight fasting has anti-cancer benefits;

• Gut bacteria may play a significant role in determining your food choices, including specifically B. vulgatus as reviewed by Dr. Eric Topol.

• A very short intervention study, just published, shows important improvements in the gut biome and health indicators of subjects who switched to a diet with unprocessed food and a probiotic (Li, et. al, 2025).

This newsletter has 2 polls. This first poll is for people who don’t want to read the Deep Dive. The second poll will be for people who read the whole newsletter. Thank you in advance for your participation as I try to understand my readers’ experience! 📚

Deep Dive

Time-Restricted Eating and the Gut Microbiome: Health Implications

Time-restricted eating (TRE) is a highly promising dietary approach that improves health outcomes in part by modifying the gut microbiome. Recent research is revealing how the timing of meals affects our microbial communities and, in turn, our health (Pérez-Gerdel et al., 2023).

Impact on Microbial Composition

Studies show that TRE can significantly change gut microbial ecology, though these changes return to baseline when the intervention stops (Pérez-Gerdel et al., 2023) suggesting that TRE is a lifestyle and not a one-time intervention. Research has documented several key changes in bacterial populations, and these appear particularly important for metabolic health and obesity resistance (Zeb et al., 2023; Ribas-Latre et al., 2024).

Some details:

• Increased Bacteroidetes and Prevotellaceae

• Decreased Escherichia, Shigella, and Peptostreptococcus

• Enhanced cyclical variety in metabolically important bacterial families

• Reintroduction of beneficial Ruminococcaceae, including Oscillibacter species

• Increased Lachnospiraceae, Parasutterella, and Romboutsia with 12-week TRE

• Enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron in shorter interventions like Ramadan fasting

How TRE Works

Time-restricted eating improves metabolic markers through the production of beneficial compounds, regulation of daily rhythms, control of metabolism, and effects on immune function (Ribas-Latre et al., 2024).

Bile Acid Signaling

TRE works partly by changing bile acid signaling, which is involved in most aspects of health, from glucose regulation to liver function, and immune competence. Lactobacillus bacteria, which increase with TRE, produce enzymes that modify bile acids, affecting both metabolism and heart health (Zeb et al., 2023).

Metabolic Control

TRE influences metabolism through several mechanisms:

1. Early-day eating reduces insulin levels throughout the day (Longo & Panda, 2016) which would be expected to reduce diabetes risk;

2. Changed bacterial populations affect brain signaling through glucocorticoid pathways (Luo et al., 2018);

3. Microbiome changes alter metabolic signaling molecules (Sonnenburg & Bäckhed, 2016), which alters how diet impacts glucose and lipid regulation.

Health Benefits

Cardiovascular Health: Recent studies show clear links between TRE-induced microbiome changes and improved heart health markers (Zheng et al., 2024).

General Health: Research shows promising effects from research in mice. TRE can:

• Increase protective bile acids like TUDCA

• Improve gut barrier function

• Increase protective goblet cells in the gut

• Reduce inflammatory cytokines in the blood

Eye Health: In mice, these changes brought about by TRE protect against diabetic eye disease (Beli et al., 2018) and may reverse age-related eye changes (Huston et al., 2024)

Stroke Protection: Changes in the microbiome caused by TRE can reduce stroke damage in animal studies (Delgado Jimenez et al., 2021).

Clinical Considerations (in humans): Several key factors affect TRE's success:

• Duration: Brief interventions (8-hour fasting) may not sufficiently change the microbiome in people with obesity (Guo et al., 2021).

• Individual Differences: Response to TRE varies significantly between people.

• Timing: Early-day eating appears most effective for metabolic benefits (Ribas-Latre et al., 2024).

Conclusion

Evidence strongly supports TRE's ability to beneficially modify the gut microbiome and improve health markers. The only thing holding me back from enthusiastically recommending that everyone adopt a TRE lifestyle is that some studies have shown loss of muscle mass. This was seen for instance in a study of individuals fasting 16 hours per day, and eating between 12 noon and 8 PM. Thus the TRE for them was both short and late in the day (Lowe et. al, 2020).

I have a tip: if you have chosen to eat within a short window (because you are trying to keep calories down) a bit too late in the day, make sure you engage in resistance training. You can gain muscle mass on TRE when you are engaged in strength training. In a 2021 study (Kotarsky), TRE subjects lost more weight than control subjects. TRE subjects gained 0.5% muscle, while control subjects gained 1.9%. The difference was not statistically significant, and neither group lost muscle mass.

In another study, young men assigned to TRE (and strength training) made improvements in muscle strength (though not muscle size) that were sometimes superior to that of the subjects who were eating normally (Tinsley).

So we can improve on Michael Pollan’s excellent health advice “Eat food. Not too much. Mostly plants.” And “stop early in the day.” But watch your muscle mass because all the research is not in.

REFERENCES

Beli E, Yan Y, Moldovan L, et al. Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice. Diabetes. 2018.

Cuervo L, McAlpine PL, Olano C, Fernández J, Lombó F. Low-Molecular-Weight Compounds Produced by the Intestinal Microbiota and Cardiovascular Disease. Int J Mol Sci. 2024.

Delgado Jiménez R, Benakis C. The Gut Ecosystem: A Critical Player in Stroke. Neuromolecular Med. 2021.

Guo Y, Luo S, Ye Y, et al. Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients. J Clin Endocrinol Metab. 2021.

Huston CA, Milan M, Vance ML, et al. The effects of time restricted feeding on age-related changes in the mouse retina. Exp Gerontol. 2024.

Kotarsky CJ, Johnson NR, Mahoney SJ, Mitchell SL, Schimek RL, Stastny SN, Hackney KJ. Time-restricted eating and concurrent exercise training reduces fat mass and increases lean mass in overweight and obese adults. Physiol Rep. 2021 May;9(10):e14868.

Li F, Armet AM, Korpela K, Liu J, Margain Quevedo R, Asnicar F, Seethaler B, Rusnak TBS, Cole JL, Zhang Z, Zhao S, Wang X, Gagnon A, Deehan EC, Mota JF, Bakal JA, Greiner R, Knights D, Segata N, Bischoff SC, Mereu L, Haqq AM, Field CJ, Li L, Prado CM, Walter J, et al. Cardiometabolic benefits of a non-industrialized-type diet are linked to gut microbiome modulation. Cell. 2025.

Li L, Yang K, Li C, et al. Metagenomic shotgun sequencing and metabolomic profiling identify specific human gut microbiota associated with diabetic retinopathy in patients with type 2 diabetes. Front Immunol. 2022.

Liu W, Wang C, Xia Y, et al. Elevated plasma trimethylamine-N-oxide levels are associated with diabetic retinopathy. Acta Diabetol. 2021.

Longo VD, Panda S. Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab. 2016.

Lowe DA, Wu N, Rohdin-Bibby L, Moore AH, Kelly N, Liu YE, Philip E, Vittinghoff E, Heymsfield SB, Olgin JE, Shepherd JA, Weiss EJ. Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial. JAMA Intern Med. 2020 Nov 1;180(11):1491-1499. Erratum in: JAMA Intern Med. 2020 Nov 1;180(11):1555. Erratum in: JAMA Intern Med. 2021

Luo Y, Zeng B, Zeng L, et al. Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus. Transl Psychiatry. 2018.

Pérez-Gerdel T, Camargo M, Alvarado M, Ramírez JD. Impact of Intermittent Fasting on the Gut Microbiota: A Systematic Review. Adv Biol (Weinh). 2023.

Ribas-Latre A, Fernández-Veledo S, Vendrell J. Time-restricted eating, the clock ticking behind the scenes. Front Pharmacol. 2024.

Shi B, Li H, He X. Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation. Gut Microbes. 2024.

Sonnenburg JL, Bäckhed F. Diet-Microbiota interactions as moderators of human metabolism. Nature. 2016.

Tinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB, Grandjean PW. Time-restricted feeding in young men performing resistance training: A randomized controlled trial. Eur J Sport Sci. 2017 Mar;17(2):200-207.

Zeb F, Osaili T, Obaid RS, et al. Gut Microbiota and Time-Restricted Feeding/Eating: A Targeted Biomarker and Approach in Precision Nutrition. Nutrients. 2023.

Zhao Y, Qiu P, Shen T. Gut microbiota and eye diseases: A review. Medicine (Baltimore). 2024.

Zheng Y, Wang J, Liu M, Zhou X, Lin X, Liang Q, Yang J, Zhang M, Chen Z, Li M, Wang Y, Sui J, Qiang W, Guo H, Shi B, He M. Time-restricted eating with or without a low-carbohydrate diet improved myocardial status and thyroid function in individuals with metabolic syndrome: secondary analysis of a randomized clinical trial. BMC Med. 2024