Revised Estimates for the Number of Human and Bacteria Cells in the Body

The paper revisits previous estimates of human and bacterial cell counts in the body, aiming to provide more accurate and detailed estimations with documented calculation logic and uncertainty ranges. Previous estimations, particularly regarding bacterial cell numbers, have often relied on rough, back-of-the-envelope calculations with limited empirical support. This study aims to address these shortcomings by integrating the most recent data and methodological approaches. A critical aspect is the re-evaluation of the commonly cited 10:1 ratio of bacterial to human cells. The study uses the "reference man" (70 kg, 20-30 years old, 170 cm tall) as a basis for its calculations, acknowledging that quantitative differences may exist for women due to variations in body mass, blood volume, and microbiota. The methodology involves a comprehensive survey of existing literature, comparison of cell counts across different body organs, and the use of both a "representative" cell size approach and a cell-type aggregation approach to estimate human cell numbers. The study also incorporates a mass-centered approach as a sanity check for its cell count estimates.

The paper reviews the literature on cell count estimations, highlighting the significant discrepancies and lack of robust measurements in prior studies. It traces the origin of prevalent claims regarding bacterial cell numbers to a single back-of-the-envelope calculation from the 1970s, which assumed a constant bacterial density across the entire alimentary tract. This study aims to improve on these older estimations by using more modern data and addressing the limitations of previous approaches. The authors review several studies that provide data on bacterial concentrations in different body organs, emphasizing the dominance of bacteria in the colon. They also examine previous estimations of human cell counts, pointing out limitations in those estimations and proposing improved methods.

The study begins by revisiting estimates of bacterial cell numbers, surveying various sources and comparing counts across different body organs. They establish the colon as the dominant contributor to the total bacterial population. A revised calculation for the total number of bacteria in the colon is presented, based on updated data on colon volume (0.4 L) and bacterial density (0.9-10¹¹ bacteria/g wet stool). This calculation incorporates uncertainty ranges derived from variation in colon volume and bacterial density. For human cells, two approaches are used. First, a 'representative' cell size approach, based on a typical mammalian cell volume and density, is employed as a sanity check. Second, a more comprehensive approach is used, focusing on the six cell types that represent 97% of the total human cell count (red blood cells, glial cells, endothelial cells, dermal fibroblasts, platelets, and bone marrow cells). For these cell types, literature values were used where possible, otherwise new calculations were derived based on more recent information. A mass-centered approach, utilizing data on the mass of main tissues in the human body and total body potassium measurements, is also used as a sanity check for the total cell mass. The study then compares the distribution of cell number and mass across different cell types, highlighting the discrepancies between the contributors to cell number and cell mass. The calculation of the bacteria to human cell (B/H) ratio is updated, considering both the total number of human cells and the number of nucleated human cells. Finally, the study assesses the variation in the B/H ratio across different population segments (women, infants, elderly, obese individuals).

The study revises previous estimates of bacterial and human cell counts in the body. The total number of bacteria in a 70kg "reference man" is estimated to be 3.8 x 10¹³, with a standard error uncertainty of 25% and a population variation of 52%. This differs significantly from previously reported values that were often orders of magnitude higher. The total number of human cells is estimated to be 3.0 x 10¹³. Approximately 90% of human cells belong to the hematopoietic lineage, predominantly red blood cells and platelets. The widely cited 10:1 ratio of bacterial to human cells is revised to approximately 1:1 (with uncertainty). The total mass of bacteria in the body is estimated to be around 0.2 kg, which is significantly lower than previous estimates. The mass-centered approach provides a sanity check for the overall cell mass, accounting for the expected body mass within acceptable limits. Analysis across different population segments shows that the B/H ratio varies by up to two-fold (1.3 to 2.3), depending on factors such as age, gender, and weight. The variation in bacterial concentration within the colon and the use of fecal samples as a proxy for colon content are highlighted as major sources of uncertainty.

The revised estimates presented in this study challenge the long-held assumption of a vast numerical dominance of bacteria over human cells in the body. The finding that the number of bacterial cells and human cells are of the same order of magnitude significantly changes our understanding of the human-microbial ecosystem. The study highlights the importance of using up-to-date information and refined methodology in making such estimates. The discrepancy between cell count and cell mass distribution underscores the complexities of analyzing cellular composition in the human body. Further research is needed to improve estimates of bacterial density in the colon, particularly addressing the limitations of using fecal samples. Additionally, research is needed to investigate the B/H ratio across a wider range of population segments and health conditions.

This study provides revised estimates for the number of human and bacterial cells in the body, incorporating updated data and rigorous methodologies. The findings challenge previously held assumptions regarding the ratio of bacterial to human cells, suggesting a more balanced distribution. The study highlights the importance of accurate quantitative data in biological research. Future research should focus on resolving the uncertainties associated with bacterial density measurements within the colon and expanding the analysis to diverse populations and health conditions. This would lead to a more complete understanding of the human-microbe relationship and its implications for health and disease.

The study primarily focuses on a "reference man", acknowledging potential differences for women. The use of fecal samples as a proxy for the average bacterial density in the colon introduces uncertainty. The study does not address the effects of factors like antibiotic use, disease, or geographic location on the B/H ratio. More research is needed to quantify systematic errors and better understand the variation in bacterial density within the colon. The lack of specific data on certain population segments (such as individuals with chronic diseases) also represent a limitation.