Exploratory analysis of one versus two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in adults with overweight/obesity

Abstract

Nutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial (ClinicalTrials.gov ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-consecutive days of IF in combination with protein pacing (IF-P; 4-5 meals/day, >30% protein/day) on the GM, the plasma metabolome, and associated clinical outcomes in overweight and obese adults. Participants (n = 20) were randomly assigned to either a diet consisting of one fasting day (total of 36 h) and six low-calorie P days per week (IF1-P, n = 10) or two fasting days (60 h total) and five low-calorie P days per week (IF2-P, n = 10). The fecal microbiome, clinical outcomes, and plasma metabolome were analyzed at baseline (week 0) and after four weeks. There were no significant time or interaction effects for alpha diversity; however, baseline alpha diversity was negatively correlated with percent body fat change after the four-week intervention (p = 0.030). In addition, beta-diversity for both IF groups was altered significantly by time (p = 0.001), with no significant differences between groups. The IF1-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and Eubacterium fissicatena group (q ≤ 0.007), while the IF2-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and a decrease in Eubacterium ventriosum group (q ≤ 0.005). The plasma metabolite profile of IF2-P participants displayed significant increases in serine, trimethylamine oxide (TMAO), levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid (q ≤ 0.049) compared to IF1-P. Fecal short-chain fatty acid concentrations did not differ significantly by time or between groups (p ≥ 0.126). Interestingly, gastrointestinal symptoms were significantly reduced for the IF2-P group but not for the IF1-P group. Our results demonstrate that short-term IF modestly influenced the GM community structure and the plasma metabolome, suggesting these protocols could be viable for certain nutritional intervention strategies.

Causal relationship between gut microbiota and prostate cancer contributes to the gut-prostate axis: insights from a Mendelian randomization study

“…The Eubacterium fissicatena group may be associated with in vivo metabolism. Nutritional investigations have shown a significant increase in the abundance of the E. fissicatena group in populations following a low-calorie diet for 6 days a week [ 34 ]. Despite the absence of specific studies on the relationship between the E. fissicatena group and prostate cancer, Zang et al discovered a causal relationship between E. fissicatena and psoriasis.…”

Pathogenic Mechanisms of the Severe Acute Respiratory Syndrome Coronavirus 2 and Potential Direct and Indirect Counteractions by Intermittent Fasting

“…The gut microbiome, including the appendix that is now recognized as a non-vestigial well that maintains the microbiome [ 72 ], is recognized today for substantial influences on human health [ 30 , 31 , 32 , 73 , 74 , 75 , 76 ]. The microbiome impacts human health, both in the prevention of or acceleration of chronic diseases and in limiting or enhancing infectious diseases [ 16 , 30 , 31 , 32 , 73 , 74 , 75 , 76 ]. This includes the potential for acute infections in the intestine or in the appendix to radically alter organ-level health [ 73 , 74 , 75 , 76 ].…”

“…Specifically, intermittent fasting modified the abundance of various microbes such as Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia , and Ruminococcaceae ( Figure 1 ) [ 31 ]. A subsequent study of once-per-week fasting compared to twice-per-week fasting found modest impacts of both fasting regimens on the microbiome, with some minor differences in the microbial diversity that was affected but generally positive results for species that improve metabolic health [ 32 ]. In that study, intermittent fasting increased the abundance of species in the Ruminococcaceae and Lachnospiraceae families ( Figure 1 ), while Eubacterium ventriosum was decreased in abundance by one form of fasting [ 32 ].…”

“…A subsequent study of once-per-week fasting compared to twice-per-week fasting found modest impacts of both fasting regimens on the microbiome, with some minor differences in the microbial diversity that was affected but generally positive results for species that improve metabolic health [ 32 ]. In that study, intermittent fasting increased the abundance of species in the Ruminococcaceae and Lachnospiraceae families ( Figure 1 ), while Eubacterium ventriosum was decreased in abundance by one form of fasting [ 32 ]. A systematic review of two types of intermittent fasting (i.e., time-restricted eating and alternate-day fasting) reported apparent effects of fasting on the microbiome such as modification of the ratio of Firmicutes/Bacteroidetes ( Figure 1 ), with metabolism-protective microbes such as Lactobacillus species and Akkermansia municiphila increased in abundance by both regimens [ 76 ].…”

“…For example, during a fasting period while energy intake is restricted, fasting may boost physiological mechanisms of human immunity specifically related to the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 15 , 16 ], activate other mechanisms related to general human immune responses [ 17 , 18 , 19 , 20 ], reduce the hyperinflammatory response to SARS-CoV-2 infection [ 21 , 22 , 23 , 24 , 25 , 26 ], and strongly induce the cellular “housecleaning” of autophagy [ 19 , 27 , 28 , 29 ]. The diet and gut-microbiota play an important role in health generally [ 13 , 18 ], and SARS-CoV-2 can cause major adverse effects on the microbiome [ 30 ], but fasting may support a healthy microbiome and increase resistance to gut dysbiosis [ 16 , 31 , 32 ]. In the long-term, fasting may improve basal levels of factors related to the response to infectious disease and to inflammation modulation [ 17 , 23 , 33 , 34 , 35 ], and generally reduce the risk and the prevalence of morbidities that are associated with worse prognosis after COVID-19 diagnosis, such as coronary artery disease, myocardial infarction, heart failure, and diabetes [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 14 , 20 , 36 , 37 , 38 , 39 , 40 ].…”